[Regional cerebral blood flow in experimental brain neoplasms].
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This study investigated the intraarterial delivery of genetically engineered replication-deficient adenovirus vectors (AVs) and cationic liposome-plasmid DNA complexes (lipoDNA) to experimental brain tumors. Adenovirus or lipoDNA was injected into the internal carotid artery (ICA) of F344 rats harboring intracerebral 9L gliosarcomas, using bradykinin (BK) to selectively permeabilize the blood-tumor barrier (BTB). Brain and internal organs of the animals were collected 48 hr after vector injection and stained for expression of the marker gene product, beta-galactosidase (beta-Gal). Intracarotid delivery of AV to 9L rat gliosarcoma without BTB disruption resulted in transgene expression in 3-10% of tumor cells distributed throughout the tumor. Virus-mediated expression of beta-gal gene products in this tumor model was particularly high in small foci (< or = 0.5 mm), which had invaded the normal brain tissue surrounding the main tumor mass. In these foci more than 50% of tumor cells were transduced. BK infusion increased the amount of transgene-expressing cells in larger tumor foci to 15-30%. In the brain parenchyma only a few endothelial cells expressed beta-gal owing to AV-mediated gene transfer. Intracarotid delivery of lipoDNA bearing a cytoplasmic expression cassette rendered more than 30% of the tumor cells positive for the marker gene without BTB disruption. The pattern of distribution was in general homogeneous throughout the tumor. BK infusion was able to increase further the number of transduced tumor cells to more than 50%. Although lipoDNA-mediated gene transfer showed increased efficacy as compared with AV-mediated gene transfer, it had less specificity since a larger number of endothelial and glial cells also expressed the transgene. AV and lipoDNA injections, in the absence and presence of BK, also resulted in transduction of peripheral organs. AV showed its known predilection for liver and lung. In the case of lipoDNA, parenchymal organs such as liver, lung, testes, lymphatic nodes, and especially spleen, were transduced. These findings indicate that intracarotid application of AV and lipoDNA vectors can effectively transduce tumor cells in the brain, and that BTB modulation by BK infusion can further increase the number of transgene-expressing tumor cells.
We measured the concentrations of chromium, cesium, and tin in the cerebrospinal fluid (CSF) of 29 patients with brain tumors [21 benign (BBT) and eight malignant (MBT)], 28 leukemic patients, 14 patients with lymphoma or noncerebral solid tumors (NLCT), and 32 control patients (15 with neurological disorders and 17 with noneurological conditions) by use of flameless atomic absorption spectrophotometry. We detected chromium in 94% of the patients, tin in 79%, and cesium in 50%. The mean (and SEM) concentrations (micrograms/L) of these metals in the control group were 4.7 (1.1) for chromium, 3.8 (1.6) for cesium, and 6.4 (1) for tin. We observed significant differences (P less than 0.05) in the concentration of chromium in CSF between the MBT group and all other tumor groups; the ratios for the mean CSF concentration of chromium in patients with BBT, leukemia, or NLCT to that in patients with MBT were 2.6, 2.1, or 4.4, respectively. We saw no significant differences in the concentrations of cesium or tin among the various groups investigated.
Epidermal growth factor (EGF) influences the cell by activation of its specific cell receptor (EGFR). It is regarded as one of the most effective mitogenic factors and plays a role in carcinogenesis. The aim of this study was the assessment of EGF expression in different types of cerebral neoplasms and searching for its correlation with histopathologic features of malignancy and presence of peritumoral oedema. Sixty seven samples of brain tumours were examined. Among them were 17 meningiomas, 34 gliomas and 16 metastases. Expression of EGF was estimated by a radioimmune assay. The authors found the presence of EGF in all types of tumours. No correlation was found between expression of EGF and histopathological signs of tumour malignancy, although a tendency appeared towards a higher level of that factor in anaplastic tumours. Also, no correlation was found between EGF and peritumoral oedema.
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