Microbiology
Zahra Gholipour; Abbas Ali Imani Fooladi; Kazem Parivar; Raheleh Halabian
Abstract
Background & Objective: Superantigens are bacterial toxins that induce a massive immune response in the host. Superantigen staphylococcal enterotoxin B (SEB) can form a ternary complex with its receptors, MHC class II (MHCII) and TCR, and can be used in tumor-targeting therapy, particularly when ...
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Background & Objective: Superantigens are bacterial toxins that induce a massive immune response in the host. Superantigen staphylococcal enterotoxin B (SEB) can form a ternary complex with its receptors, MHC class II (MHCII) and TCR, and can be used in tumor-targeting therapy, particularly when cooperating with a specific vector. In this study, SEB was fused to interleukin-13 (IL13), which forms a complex with IL13 receptor α2 (IL13Rα2) overexpressed in glioblastoma multiforme (GBM) cells for therapeutic goals.Methods We designed four fusion proteins based on the arrangement of SEB (N- or C-terminal domain) and provided a flexible inter-domain linker (no or yes), resulting in the formation of SEB-IL13, SEB-L-IL13, IL13-SEB, and IL13-L-SEB, respectively. These fusion proteins were then evaluated for their various physicochemical properties and structural characteristics. Bioinformatics tools were employed to predict, refine, and validate the three-dimensional structure of the fusion proteins. In addition, the fusion proteins were docked with IL13Rα2, MHCII, and TCR receptors through the HADDOCK 2.4 server. The candidate fusion protein was subjected to molecular dynamics simulation.Results: There were differences among the designed fusion proteins. The model with the N-terminal domain of IL13 and containing an inter-domain linker (IL13-L-SEB) was stable and had a long half-life. The docking analysis revealed that the IL13-L-SEB fusion protein had a higher binding affinity to the IL13Rα2, MHCII, and TCR receptors. Finally, using molecular dynamics simulation through iMODS, acceptable results were obtained for the IL13-L-SEB docked complexes.Conclusion: The results suggest IL13-L-SEB is a promising novel fusion protein for cancer therapeutic application.
Noushin Afshar Moghaddam; Parvin Mahsuni; Diana Taheri
Abstract
Background and Objectives: Angiogenesis is essential for growth and metastasis of solid malignancies. Tumor vessel count and expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, have been associated with prognosis. This study was designed to assess vessels density by using ...
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Background and Objectives: Angiogenesis is essential for growth and metastasis of solid malignancies. Tumor vessel count and expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, have been associated with prognosis. This study was designed to assess vessels density by using CD31 and CD105 (Endoglin) and their correlation with expression of VEGF and proliferative index (Ki67) in Glioblastoma multiforme (GBM). Methods: We examined these parameters in GBM specimens from 50 adult patients; referred to AlZahra hospital Pathology Lab between 2001 to 2006.These patients did not receive pre-operative therapy. Paraffin-embedded tumor specimens were immunohistochemically stained for CD31, CD105 (Endoglin), VEGF and Ki67 (proliferation index) monoclonal antibodies. Microvessel density (MVD) was evaluated by immunostaining for CD31 and CD105.Then the results were compared between the two and also with VEGF receptors and Ki67 index. Results: CD105-MVD was significantly higher in Glioblastoma compared with peritumoral normal (14.28 vs. 6.68: P=0.012). We did not find such difference for CD31. The mean of CD105-MVD was significantly higher than CD31-MVD in Glioblastoma tissue (P<0.001) although there was a significant positive relationship between them (Pearson’s r=0.630 P<0.001).The VEGF scoring for tumoral tissue was 12 % (score:1), 46% (score:2) and 42% (score:3).For peritumoral normal tissue were 92% (score:1) and 8% (score:2) . So they reach to statistical significance (Chi Square, P= 001). Both MVD of CD105 and CD31 have significant relationship with VEGF (P<0.001). Conclusion: We suggest that Endoglin can be used as a specific and sensitive marker for evaluation of angiogenesis in Glioblastoma.
