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- Carlsson, J, et al.
(författare)
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Strategy for boron neutron capture therapy against tumor cells with over-expression of the epidermal growth factor-receptor.
- 1994
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016 .- 1879-355X. ; 30:1, s. 105-15
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Gliomas, squamous carcinomas and different adenocarcinomas from breast, colon and prostate might have an increased number of epidermal growth factor (EGF) receptors. The receptors are, in these cases, candidates for binding of receptor specific toxic conjugates that might inactivate cellular proliferation. The purpose of this study was to evaluate whether it is reasonable to try ligand-dextran based conjugates for therapy.METHODS AND MATERIALS: EGF or TGF alpha were conjugated to dextran and binding, internalization, retention and degradation of eight types of such conjugates were analyzed in EGF-receptor amplified glioma cells. The conjugates were labelled with radioactive nuclides to allow detection and two of the conjugates were carrying boron in the form of carboranyl amino acids or aminoalkyl-carboranes. Comparative binding tests, applying 125I-EGF, were made with cultured breast, colon and prostate adenocarcinoma, glioma and squamous carcinoma cells. Some introductory tests to label with 76Br for positron emission tomography and with 131I for radionuclide therapy were also made.RESULTS: The dextran part of the conjugates did not prevent receptor specific binding. The amount of receptor specific binding varied between the different types of conjugates and between the tested cell types. The dextran part improved intracellular retention and radioactive nuclides were retained for at least 20-24 h. The therapeutical effect improved when 131I was attached to EGF-dextran instead of native EGF.CONCLUSION: The improved cellular retention of the ligand-dextran conjugates is an important property since it gives extended exposure time when radionuclides are applied and flexibility in the choice of time for application of neutrons in boron neutron capture therapy (BNCT). It is possible that ligand-dextran mediated BNCT might allow, if the applied neutron fields covers rather wide areas around the primary tumor, locally spread cells that otherwise would escape treatment to be inactivated.
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| 2. |
- Holtz, A, et al.
(författare)
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Blocking weight-induced spinal cord injury in rats : therapeutic effect of the 21-aminosteroid U74006F.
- 1991
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 8:4, s. 239-45
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Tidskriftsartikel (refereegranskat)abstract
- The effect of the 21-aminosteroid U74006F on neurologic recovery after a spinal cord compression trauma was investigated in rats. The compression was induced by a blocking weight technique, in which a 35 g (moderate injury) or a 50 g (severe injury) weight was applied for 5 minutes to an 11 mm2 plate over the midthoracic spinal cord. One hour after trauma, the severely injured animals were treated either with U74006F, 3 mg/kg, methylprednisolone, 30 mg/kg, or vehicle, whereas the moderately injured animals received U74006F, 3 mg/kg or vehicle. Neurologic hind limb function was evaluated by the inclined plane technique. On day 1 after trauma, subtotal paraparesis occurred in the 35 g group treated with vehicle (31 +/- 1 degrees, mean +/- SEM) on the inclined plane vs 64 +/- 1 degrees before trauma) and complete paraplegia in the 50 g group (22 +/- 1 degrees). Treatment with U74006F resulted in less hind limb weakness in the 35 g group (42 +/- 2 degrees) but had no beneficial effect in the 50 g group (25 +/- 2 degrees). Neurologic function gradually improved in the 35 g groups over the 9-day observation period. However, those animals treated with U74006F were significantly better over the entire period. In the 50 g group, no recovery from paraplegia was noted over the 4 day observation period in any of the three groups. These results suggest that after weight-induced spinal cord trauma, U74006F is associated with improved neurologic function in moderately injured, but not severely injured animals.
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