Marked neovascularization is a hallmark of many neoplasms in the nervous system. Recent reports indicate that the endothelial
mitogen vascular endothelial growth factor (VEGF) may play a critical role in the regulation of vascular endothelial proliferation
in malignant gliomas. Using novel monoclonal antibodies to the VEGF polypeptide we have determined the expression and cellular
distribution of VEGF protein in a representative series of 171 human central nervous system (CNS) tumors by immunohistochemistry
and immunoblotting. In agreement with previous in situ hybridization data, 19 out of 20 glioblastomas (95%) showed immunoreactivity
for VEGF, whereas both the percentage of immunoreactive tumors and the extent of immunoreactivity for VEGF were significantly
lower in astrocytomas. Of the pilocytic astrocytomas (WHO grade I) 44% were immunoreactive for VEGF, but we observed several
cases with pronounced vascular proliferates in the absence of VEGF. In ependymomas, meningiomas, hemangioblastomas, and primitive
neuroectodermal tumors, there was no correlation between VEGF expression, vascular endothelial proliferation and the grade
of malignancy. Oligodendrogliomas and the oligodendroglial component of mixed gliomas lacked immunoreactive VEGF, indicating
that endothelial growth factors other than VEGF may regulate tumor angiogenesis in these neoplasms. Western blot analysis
showed a predominant VEGF protein species of 23 kDa and confirmed the immunohistochemical data in all cases. Our findings
demonstrate that VEGF is expressed in a wide spectrum of brain tumors in which it may induce neovascularization. However,
other angiogenic factors also appear to contribute to the vascularization of CNS neoplasms.
Received: 18 April 1996 / Revised, accepted: 20 August 1996 相似文献
Summary Thoracoscopic surgery is decidedly expanded by the ability to perform pulmonary wedge resections of the lung by using the Endo-GIA-stapler. In addition to thoracoscopic biopsies, since July 1991 we have carried out wedge resections in 12 patients suffering from spontaneous pneumothorax (nine) or peripheral bronchial carcinoma (three). Postoperatively one air fistula persisted over 9 days. The chest tube was removed within 48 h in all other patients. There was no other major complication. The postoperative hospitalization period lasted 4.6 days (1–9 days). Operating time was 44 min (30–70 min). The benefit for the patient consists in the little-impaired breathing mechanics, the short hospital stay, and the favorable cosmetic result. 相似文献
Summary Cell proliferation of 51 human renal cell carcinomas and 9 larynx and hypopharynx carcinomas has been studied in vitro and using xenotransplants. The proliferative activity ([3H]thymidine labelling index) increases during the first passages in nude mice and then remains almost constant throughout subsequent passages. A comparison of cell kinetic parameters of 8 human renal cell carcinomas, 1 hypopharynx and 2 larynx carcinomas, with data of xenografts and of human tumours in situ published up to now, shows that the cell kinetic parameters of human tumour xenografts presently studied range between those of human tumours in situ and those of autochthonous or transplantable mouse tumours. S-phase durations and potential doubling times are considerably shorter in xenotransplants than in human tumours in situ, whereas the cycle time is about the same. This means that the growth fraction increases considerably after xenotransplantation. This change of human tumour cell proliferation after transplantation into nude mice should be kept in mind if one wishes to draw conclusions from the nude mouse model on conditions in human beings, particularly with respect to therapeutic regimens, which are frequently tested in the nude mouse model.Abbreviations used RCC
renal cell carcinoma
- HPC
larynx or hypopharynx carcinoma
- LI
labelling index
- PLM
percentage of labelled mitoses
-
ts
S-phase duration
-
tc
cycle time
-
tpot
potential doubling time
This work was supported by the Deutsche Forschungsgemeinschaft (Ma 876/2-1) 相似文献
Autoradiographic techniques were used to test if positive modulators of AMPA-type glutamate receptors have regionally differentiated effects on ligand binding. Cyclothiazide, a drug with ten fold greater effects on `flip' than `flop' splice variants of the receptors, had unequal effects across the subdivisions of hippocampus; i.e., it reduced [3H]AMPA binding in field CA3 with an EC50 of 24 μM and in field CA1 and dentate gyrus with EC50s between 60 and 100 μM. The EC50 for the drug's influence on binding was also significantly lower in the superficial than in the deeper layers of the neocortex, though these differences were not as pronounced as those in the hippocampus. The ampakine CX614, a compound with a modest preference for flop variants, had a slightly lower EC50 for its effects on [3H]AMPA binding in CA1 than in CA3. This result was confirmed with [3H]fluorowillardiine binding. The effects of the ampakine in neocortex tended to be greater in the deeper than superficial layers but this did not reach statistical significance. These results indicate that differential effects of modulators on AMPA receptor subunits are reflected in their relative potency across brain subdivisions. This raises the possibility that subclasses of positive modulators will exhibit a measurable degree of selectivity in their physiological and behavioral influences. 相似文献
The shear modulus of the vocal fold is an essential parameter required to enhance our understanding of how the vocal fold
operates, to develop mathematical models of phonatation, and to provide benchmarks to quantify the effectiveness of surgical
procedures. The authors announced the successful deployment of an instrument to measure vocal fold elasticity in vivo last
year, and now present the data taken from eight patients in vivo. The shear modulus was measured at the mid-membranous point,
in a transverse direction with respect to the axis drawn between the anterior commissure and vocal process. The range of mean
shear modulus results is 701–2,225 Pa, with a mean value of 1,371 Pa. 相似文献
Background: Liver dysfunction as a result of impaired oxygen availability frequently occurs following hemorrhage and contributes to delayed mortality. Artificial oxygen carriers may improve oxygen supply to vital organs while avoiding the need for allogeneic transfusion.
Methods: Rats were subjected to hemorrhagic hypotension (mean arterial pressure = 35-40 mmHg for 120 min) and were subsequently resuscitated with (1) stored whole rat blood, (2) pentastarch, or (3) pentastarch combined with perflubron emulsion (PFE; 2.7 or 5.4 g/kg body weight), a second-generation artificial oxygen carrier. Recovery of liver adenosine triphosphate, hepatocellular injury, and expression of glutamine synthetase 1, a gene that is induced by exposure of hepatocytes to low partial pressure of oxygen, were studied at 4 h of resuscitation.
Results: Stored whole blood or pentastarch failed to restore liver adenosine triphosphate concentrations after prolonged shock as compared to sham controls and resulted in increased gene expression of glutamine synthetase 1. Addition of 2.7 g PFE/kg restored liver adenosine triphosphate to control, whereas 5.4 g PFE/kg resulted in adenosine triphosphate concentrations significantly above control. Improved hepatocellular oxygen supply was also confirmed by restoration of the physiologic expression pattern of glutamine synthetase 1. Serum enzyme concentrations were highest after resuscitation with stored blood, whereas addition of PFE failed to further decrease enzyme concentrations as compared to pentastarch alone. 相似文献
The contribution of (18)F-FDG uptake by endothelial cells to uptake values measured by PET in various tissues is as yet unclear. We therefore sought to characterize (18)F-FDG uptake in an in vitro model of human endothelial cells. METHODS: Commercially obtained human umbilical vein endothelial cells (HUVECs) were seeded in 6-multiwell plates 48-96 h before incubation with 1-2 MBq (18)F-FDG per well. Radioactivity measurements were performed after washing and mechanical dissolvation of the cellular monolayers. Cellular (18)F-FDG uptake was referred to protein concentration. This experimental protocol was subsequently varied to study the effect of different parameters of interest. Furthermore, radio-thin-layer chromatography was used to identify intracellular (18)F-FDG metabolites. (18)F-FDG uptake in HUVECs was compared with that by a human monocyte-macrophage (HMM) preparation and by glioblastoma cells (GLIOs) under identical experimental conditions. RESULTS: (18)F-FDG accumulated in HUVECs in a time-dependent manner and was trapped mainly as (18)F-FDG-6-phosphate and (18)F-FDG-1,6-diphosphate. Unlabeled glucose and cytochalasin B competitively inhibited (18)F-FDG uptake, whereas phlorizin had no significant effect. Glucose deprivation significantly enhanced (18)F-FDG uptake by a factor of 2.7, whereas sodium depletion had no significant influence. HUVECs treated with vascular endothelial growth factor (VEGF) showed a significant 82% increase in (18)F-FDG accumulation after a 2-h exposure to 50 ng/mL VEGF. (18)F-FDG uptake in HUVECs was significantly higher than that in HMMs and in the range of the uptake values measured in GLIOs. CONCLUSION: (18)F-FDG accumulates in HUVECs by mechanisms analogous to those in neoplastic cells or neurons. VEGF significantly stimulates endothelial (18)F-FDG uptake. The observed differences in (18)F-FDG uptake between HUVECs, HMMs, and GLIOs are difficult to extrapolate to in vivo conditions but stimulate further studies on the contribution of endothelial (18)F-FDG uptake to the overall uptake of that tracer in neoplastic or vascular lesions. 相似文献