Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells.

Glioblastoma multiforme (GBM) is the most common subtype of primary malignant brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used successfully in clinical trials for GBM, the capacity of Ads to infect human glioma cells and the expression of adenoviral receptors in GBM cells have been challenged. In this report, we studied the expression of three molecules that have been shown to mediate adenoviral entry into cells, i.e., coxsackie and adenovirus receptor (CAR), integrin alphavbeta3 (INT), and major histocompatibility complex class I (MHCI), in rodent glioma cell lines and low-passage primary cultures and cell lines from human GBM. We correlated levels of expression of CAR, INT, and MHCI with transduction efficiency elicited by several high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of adenoviral receptors were variable among the different GBM cells studied. HC-Ad-mediated therapeutic gene expression was efficient, ranging between 20 and 80% of the total target cells expressing the encoded transgenes. Our results show no correlation between the levels of CAR, INT, or MHCI molecules and the levels of transgene expression or the number of GBM cells transduced. We conclude that expression levels of adenoviral receptors do not predict their transduction efficiency or biological function.     

Soluble polystyrene derivatives of metal bis(3,4-dicarboxybenzoyl)phthalocyaninates: Synthesis,thermal analysis,and sensitivity towards toxic gases

Polystyrene-bound metal [2,9 or 2,10 (or 2,16 or 2,17) bis(3,4-dicarboxybenzoyl)]phthalocyaninates were synthesized by Friedel-Crafts reaction of polystyrene with the corresponding metal phthalocyaninates. Co(II) and Cu(II) [2,9 or 2,10 (or 2,16 or 2,17) bis(3,4-dicarboxybenzoyl)]-phthalocyaninate (PS-CodaPc and PS-CudaPc) contained 0,13 mmol · g^?1 (12,4 wt.-%) and 0,13 mmol · g^?1 (12,8 wt.-%) of CodaPc and CudaPc, respectively. They were soluble in N,N'-dimethylformamide, but only partially soluble in chloroform, tetrahydrofuran (THF), dimethyl sulfoxide, N-methyl-2-pyrrolidone, and pyridine. The THF extracts contained 0,12 mmol · g^?1 (11,4 wt.-%) and 0,18 mmol ? g^?1 (17,2 wt.-%) of PS-CodaPc and PS-CudaPc, respectively. The thermal stability of the polymers was studied using thermogravimetric and differential thermal analysis in nitrogen and synthetic air atmosphere. The contents of MdaPc(M: metal) in THF-extracted polymers calculated from the data of residue in thermogravimetric analysis are 0,12 mmol · g^?1 for PS-CodaPc and 0,19 mmol · g^?1 for PS-CudaPc. In addition, the sensitive properties of the polymers towards toxic gases were also investigated by quartz microbalance transducers. The results show that the quartz microbalance sensors coated with both polymers were sensitive to NO₂ and chlorinated hydrocarbons, i.e. chloroform and perchloroethylene. The sensitivity to NO₂ was 6,53 · 10^?7 m³ · mL^?1 · s^?1 for PS-CodaPc and 1,90 · 10^?6 m³ · mL^?1 · s^?1 for PS-CudaPc, and that to chloroform and perchloroethylene was 2,33 · 10^?8 and 4,60 · 10^?8 m³ · mL^?1 · s^?1, respectively, for PS-CodaPc and 4,79 · 10^?8 and 9,51 · 10^?7 m³ · mL^?1 · s^?1 for PS-CudaPc.