Antitumor effects of combined transfer of suicide and cytokine genes were investigated in this study. Adenovirus harboring E. coli cytosine deaminase gene (AdCD) and adenovirus harboring murine granulocyte-macrophage colony-stimulating factor gene (AdGMCSF) were used simultaneously for in vivo gene transfer in melanoma-bearing mice. Growth inhibition of established tumors and prolongation of survival period were observed more significantly in tumor-bearing mice after transfection with AdGMCSF and AdCD followed by continuous injection of prodrug 5-fluorocytosine (5FC) when compared with mice treated with control adenovirus AdlacZ/5FC, AdCD/5FC or AdGMCSF alone (P < 0.01). After combined therapy the expression of MHC-I (H-2Db) and B7-1 molecules on freshly isolated tumor cells increased greatly and more dendritic cells and CD8+ T cells infiltrated into the tumor mass. The activity of specific cytotoxic T lymphocytes was also found to be induced more significantly after the combined therapy. Further experiments showed that apoptosis of tumor cells and induction of antitumor immune response might be involved in the mechanisms of the tumor cell killing by the combined therapy. Our results demonstrated that combined transfer of the GM-CSF and CD suicide genes, being able to inhibit the growth of melanoma synergistically and induce specific antitumor immune response efficiently, thus addressing the drawbacks of suicide gene therapy or cytokine gene therapy which were proved to be not satisfactory when used alone, might be of therapeutic potential for gene therapy of cancer. 相似文献
Oral delivery is the preferred route of drug administration. However, the breakdown of molecules and low levels of absorption in the gastrointestinal system render the oral delivery of proteins and peptides ineffective. Bioadhesive delivery devices can be used to circumvent these problems by protecting the drug from gastrointestinal denaturation, localizing and prolonging a drug at a specific target site, and maintaining direct contact with the intestinal cells, thereby increasing the drug concentration gradient. Microfabrication technology may offer some potential advantages over conventional delivery technologies. The benefits of microfabrication include the ability to tailor the size, shape, reservoir volume, and surface characteristics of the drug delivery vehicle. In this study, bioadhesive properties were introduced to microfabricated poly(methyl methacrylate) (PMMA) microdevices by attachment of lectins, a group of proteins capable of specifically targeting cells in the gastrointestinal tract. In this process, the PMMA microdevices were chemically modified by aminolysis to yield amine-terminated surfaces. Avidin molecules were covalently bound to the surface of the particles using a hydroxysuccinimide catalyzed carbodiimide reagent and then incubated in an aqueous solution of biotinylated lectin. The lectin-modified microdevices were examined in vitro in terms of their bioadhesive characteristics. 相似文献
To compare the diagnostic performance of 5-point scoring system and strain ratio by sonoelastography in the assessment of solid breast lesions.
Material and methods
One hundred and eighty-seven solid masses in 155 patients were scanned by two-dimensional ultrasonography and sonoelastography. Elasticity scores were determined with a 5-point scoring method, and the strain ratio was based on the comparison of the average strain measured in the lesion with the adjacent breast tissue in the same depth. Pathological results were taken as gold standards to compare the diagnostic efficacy of two methods with clinical diagnostic test and receiver operating characteristic (ROC) curves.
Results
Among 187 lesions, 130 were benign and 57 were malignant. The mean scores (1.62 ± 0.69 vs 4.07 ± 0.26, P < 0.05) and strain ratios (2.06 ± 1.27 vs 6.66 ± 4.62, P < 0.05) were significantly higher of malignant than benign lesions. The area under the curve for the 5-point scoring system and for strain ratio-based elastographic analysis was 0.892 and 0.909, respectively (P > 0.05). For 5-point scoring, sonoelastography had 84.2% sensitivity, 84.6% specificity, 84.5% accuracy, 70.6% positive predictive value and 92.4% negative predictive value. When a cutoff point of 3.06 was used, sensitivity, specificity, accuracy, positive and negative predictive values were 87.7%, 88.5%, 88.2%, 76.9% and 94.3%, respectively for the strain ratio (P > 0.05).
Conclusions
The 5-point scoring system and strain ratio has similar diagnostic performance, and the strain ratio could be more objective to differentiate the masses when those masses were difficult to be judged by using 5-point scoring system in sonoelastographic images. 相似文献
Objective: CHA2DS2-VASc is the extension of the CHADS2 score developed by Birmingham 2009. This risk stratification schema is often used in clinical setting when considering additional risk factors for developing stroke in AF patients. However, its role in the non-AF population is unknown. This study was designed to evaluate the accuracy of the CHADS2 and the CHA2DS2-VASc scoring systems.
Methods: Studies designed for CHADS2 and CHA2DS2-VASc score in stratifying the risks for stroke development in non-AF patients were included.
Results: Among the 114 studies identified, six trials were chosen finally and included for meta-analysis. The pooled diagnostic odds ratio (DOR) for CHADS2 and CHA2DS2-VASc was 2.86 (95% CI =1.83–4.28) and 2.80 (95% CI =1.83–4.28), respectively. CHA2DS2-VASc score was of better sensitivity than CHADS2 score (0.920 vs. 0.768). However, both scores were showed to have inherent heterogeneity and poor specificity.
Conclusions: Though having good diagnostic accuracy, the clinical application of the CHADS2 and CHA2DS2-VASc scores in predicting risk of stroke development in non-AF patients still needs further validation.
Key message
The overall diagnostic accuracy of CHADS2 and CHA2DS2-VASc in stroke-risk stratification was good in patients with non-atrial fibrillation.