In Vitro Assessment of Dose-Dependent Platelet Activation by Polyclonal Antithymocyte Globulins: A Flow-Cytometric Analysis

2004 ◽  
Vol 78 (5) ◽  
pp. 751-754 ◽  
Author(s):  
Andres Beiras-Fernandez ◽  
Sebastian Walther ◽  
Silvia Muenzing ◽  
Eckart Thein ◽  
Claus Hammer
1999 ◽  
Vol 7 (2) ◽  
pp. E5
Author(s):  
Roger Breyer ◽  
Sami Hussein ◽  
Dorel L. Radu ◽  
Klaus-Martin Pütz ◽  
Sven Gunia ◽  
...  

Glioblastoma multiforme (GBM) invasiveness is a complex process that involves recognition and attachment of GBM cells to particular extracellular matrix (ECM) molecules prior to migrating into proteolytically modified matrix and inducing angiogenesis. The CD44, which is a transmembrane adhesion molecule found on a wide variety of cells including GBM, has been suggested as the principal mediator of migration and invasion. The aim of the present study was to demonstrate whether an antibody specific to the standard form of CD44 (CD44s, 85-90 kDa) might prevent invasion and thus disrupt progression of C6 GBM in vivo. Immunostaining demonstrated homogenous expression of CD44s on the surface of C6 GBM cells and tumors. Flow cytometric analysis demonstrated binding saturation of anti-CD44s mAb to the receptor at 1 μg/5 X 105 cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive (up to 94 ± 2.7%; mean ± standard deviation [SD]) detachment of C6 cells from ECM-coated culture surfaces. Blocking of CD44s in vivo resulted in significantly reduced C6 brain tumors (3.6 ± 0.4% [SD])--measured as the quotient: tumor surface (mm2)/brain surface (mm2) X 100--as compared with untreated (19.9% ± 0.9%) or sham-treated rats (19.2 ± 1.1% to 19.3 ± 2.5% [SD]). Disruption of C6 GBM progression correlated with an improved food intake; treated rats were significantly less cachectic (166.6 ± 16.4 g [SD]) than those that were untreated (83.0 ± 2.7 g [SD]) or sham-treated (83.4 ± 1.1 g to 83.0 ± 2.2 g [SD]) rats. The authors conclude that CD44s-targeted treatment with specific mAb may represent an effective means for preventing progression of highly invasive GBMs.


2016 ◽  
Vol 36 (10) ◽  
pp. 1059-1070 ◽  
Author(s):  
MBO Chagas ◽  
NCC Cordeiro ◽  
KMR Marques ◽  
MG Rocha Pitta ◽  
MJBM Rêgo ◽  
...  

A series of new thiazacridine agents were synthesized and evaluated as antitumor agents, in terms of not only their cytotoxicity but also their selectivity. The cytotoxicity assay confirmed that all compounds showed cytotoxic activity and selectivity. The new compound, 3-acridin-9-ylmethyl-5-(5-bromo-1 H-indol-3-ylmethylene)-thiazolidine-2,4-dione (LPSF/AA29 – 7a), proved to be the most promising compound as it presents lower half-maximal inhibitory concentration (IC50) values (ranging from 0.25 to 68.03 µM) depending on cell lineage. In HepG2 cells, the lowest IC50 value was exhibited by 3-acridin-9-ylmethyl-5-(4-piperidin-1-yl-benzylidene)-thiazolidine-2,4-dione (LPSF/AA36 – 7b; 46.95 µM). None of the synthesized compounds showed cytotoxic activity against normal cells (IC50 > 100 µM). The mechanism of death induction and cell cycle effects was also evaluated. Flow cytometric analysis revealed that the compounds LPSF/AA29 – 7a and LPSF/AA36 – 7b significantly increased the percentage of apoptotic cells and induced G2/M arrest in the cell cycle progression. Therefore, these new thiazacridine derivatives constitute promising antitumor agents whose cytotoxicity and selectivity properties indicate they have potential to contribute to or serve as a basis for the development of new cancer drugs in the future.


2019 ◽  
Vol 35 (9) ◽  
pp. 577-592 ◽  
Author(s):  
Srijita Chakrabarti ◽  
Danswrang Goyary ◽  
Sanjeev Karmakar ◽  
Pronobesh Chattopadhyay

Health hazards of titanium dioxide nanoparticles (TiO2-NPs) have raised severe concerns because of the paucity of information regarding the toxic effects among the population. In the present research, the in vitro and in vivo cytotoxic potential of TiO2-NPs were evaluated using flow cytometric techniques. Further, in vitro and in vivo genotoxic endpoints were estimated by means of comet, micronucleus (MN), and chromosomal aberration (CA) assays. In vitro analysis was performed at the concentration range of 10–100 µg/mL using murine RAW 264.7 cells. In vivo experiments were conducted on Albino mice (M/F) by exposing them to 200 and 500 mg/kg TiO2-NPs for 90 days. Decreased percentage of cell viability with higher doses of TiO2-NPs was evident in both in vitro and in vivo flow cytometric analysis. Further, an impaired cell cycle (G0/G1, S, and G2/M) was reflected in the present investigation following the exposure to TiO2-NPs. Increased comet scores such as tail length, % DNA in tail, tail moment, and olive moment were also observed with the higher doses of TiO2-NPs in vitro and in vivo comet assays. Finally, the in vivo MN and CA assays revealed the formation of MN and chromosomal breakage following the exposure to TiO2-NPs.


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