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Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells. 总被引:2,自引:0,他引:2
Marianela Candolfi James F Curtin Wei-Dong Xiong Kurt M Kroeger Chunyan Liu Altan Rentsendorj Hasmik Agadjanian Lali Medina-Kauwe Donna Palmer Philip Ng Pedro R Lowenstein Maria G Castro 《Molecular therapy》2006,14(3):371-381
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. 相似文献
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Rongnong Zhou Ligong Tang Kurt E. Geckeler Wolfgang Gpel 《Macromolecular chemistry and physics.》1994,195(7):2409-2421
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. 相似文献
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Senta Graf Mariann Gy?ngy?si Aliasghar Khorsand Stephan G Nekolla Christian Pirich Kurt Kletter Robert Dudczak Dietmar Glogar Gerold Porenta Heinz Sochor 《Journal of nuclear medicine》2004,45(10):1611-1618
The aim of this study was to compare nonfluoroscopic electroanatomic mapping (NOGA), SPECT perfusion imaging, and PET metabolic imaging for assessment of myocardial viability. In particular, we sought to elucidate differences of electromechanical properties between the perfusion/metabolism mismatch as an indicator of a potentially reversible ischemic injury and the perfusion/metabolism match indicating irreversibly damaged myocardial tissue. METHODS: Twenty-one patients with coronary artery disease underwent NOGA mapping of endocardial unipolar voltage, cardiac 18F-FDG PET of glucose utilization, and resting 201Tl SPECT of myocardial perfusion. RESULTS: Electrical activity was 10.8 +/- 4.6 mV (mean +/- SD) in normal myocardium and was unchanged in hypoperfused segments with maintained glucose metabolism (perfusion/metabolism mismatch), 9.3 +/- 3.4 mV (P = not significant). In contrast, hypoperfused segments with a perfusion/metabolism match and nonviable segments showed significantly lower voltage (6.9 +/- 3.1 mV, P < 0.0001 and 4.1 +/- 1.1 mV, P < 0.0001 vs. normal). In hypoperfused segments, metabolic activity was more closely related to endocardial voltage than was myocardial perfusion (201Tl vs. voltage: r = 0.38, SEE = 3.2, P < 0.001; 18F-FDG PET vs. voltage: r = 0.6, SEE = 2.8, P < 0.0001). CONCLUSION: In hypoperfused myocardium, electrical activity by NOGA mapping is more closely related to PET metabolic activity than to SPECT myocardial perfusion. As NOGA mapping does not differentiate hypoperfused myocardium with enhanced glucose utilization from normal myocardium, results from NOGA mapping need to be correlated with results from perfusion imaging to identify hypoperfused, yet viable, myocardium and to stratify patients for revascularization procedures. 相似文献
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Encephalopathy is a common complication of sepsis. However, little is known about the morphological changes that occur in the brain during sepsis. In this study, fecal peritonitis was induced in Wistar rats, which had been monitored for 4 h before their brains were removed and samples from the CA1 area taken. In addition to higher blood pressure with a decreasing pattern and a significant drop in rectal temperature, an increased heart rate and marked respiratory failure were observed. The tissue was investigated and compared with corresponding hippocampal samples taken from sham‐operated and not operated control groups. Significantly more peri‐microvascular edema was found in the hippocampal CA1 area in the septic group. The percentages of the peri‐microvascular edema were 158.57 ± 3.6%, 122.84 ± 1.5% and 120.24 ± 1.9% in the fecal peritonitis group, sham‐operated and not operated control groups, respectively. The results may suggest that the edema observed around the microvessels may participate in the pathogenesis of the septic encephalopathy probably by causing in the microvascular permeability characteristics. 相似文献
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A 3.5-year-old boy with orbital and central nervous system extension of unilateral retinoblastoma received chemotherapy consisting of intravenous cyclophosphamide and doxorubicin and intrathecal methotrexate. Complete shrinkage of orbital tumor, phthisis bulbi,'and disappearance of intracranial metastases occurred following chemotherapy. Response of the intra-cranial tumors reflected the combined effects of cyclophosphamide and doxorubicin; the contribution of each agent could not be assessed. Cerebrospinal fluid tumor cells persisted prior to delivery of craniospinal irradiation, and were detected again 6 weeks after completion of irradiation. 相似文献
30.
Richard F. Lee Kurt C. Pice Vassilis C. Stamoudis 《Archives of environmental contamination and toxicology》1988,17(5):651-656
A liquid Chromatograph equipped with a short (3 cm) reverse phase column and electrochemical detector was used to characterize aromatic amines in shale oil, synthetic oil, and coal gasification streams. Five major peaks were produced from each sample mixture. The composition of the peaks was determined by high performance liquid chromatography with a long (25 cm) reverse phase column and by gas chromatography/mass spectrometry. Amines in the various peaks included aminonaphthalenes, aminobiphenyls, aminofluorenes, and aminophenanthrenes plus aminoanthracenes. The concentration of aminofluorenes, and aminophenanthrenes plus aminoanthracenes correlated with relative mutagenicity of the base fraction from the oils or tars. The levels of 2- and 3-ringed aromatic amines from shale oil and oil from the Great Plains commercial coal gasification plan were 24 and 184 g/g tar, respectively, while the respective mutagenicities were 8 and 214 revertants/g base fraction. This technique has the advantages of high sensitivity and rapid analysis, and could be used to screen for the presence of mutagens in synthetic fuel samples. 相似文献