The effect of ricin B chain on the intracellular trafficking of an A chain immunotoxin.
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Covalent linkage of the A chain of ricin to the LICR-LOND-Fib75 monoclonal antibody produced an immunotoxin, Fib75-SS-ricin A, which demonstrated immunospecific toxicity to human bladder carcinoma cells in tissue culture (Forrester et al., 1984). The present studies have shown that ricin B chain potentiates the toxicity of the immunotoxin by two orders of magnitude and also significantly increases the rate of protein synthesis inhibition. Using immunoelectron microscopy, the receptor-mediated endocytosis and intracellular routing of the immunotoxin was studied with and without ricin B chain treatment after immunolocalisation of the conjugate. Fib75-SS-ricin A was internalised by the EJ cells predominantly in uncoated pits and vesicles and directed to the endosomes. Some degradation of the complex appeared to take place in multivesicular endosomes at early timepoints and 24 h after internalisation, most of the immunotoxin was found in lysosomes. Some ricin A chain epitopes were detected in Golgi vesicles. Cells treated with immunotoxin and ricin B chain endocytosed the complex predominantly in coated pits and coated vesicles. Using pre-embedding immunoperoxidase techniques, ricin chains were found in the whole Golgi complex and most of the conjugate escaped lysosomal degradation. Internalised immunotoxin was recycled back to the plasma membrane in an active form associated with vesicles which appeared to be derived predominantly from multivesicular endosomes. A similar mode of recycling has recently been reported (McIntosh et al., 1990) for ricin holotoxin in the same cell line. These observations may explain the potentiating effect of toxin B chains in the antibody-directed targeting of toxin A chains. (+info)
Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration.
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Low-dose-rate interstitial brachytherapy preserves good quality of life in buccal mucosa cancer patients.
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PURPOSE: To determine the results and long-term changes in radiation toxicity of stage I-II buccal mucosa cancer patients treated by low-dose-rate (LDR) brachytherapy with (198)Au grains. MATERIALS AND METHODS: A total of 133 stage I-II buccal mucosa carcinomas patients received (198)Au grain implantation brachytherapy between January 1982 and July 2005: 75 of them were treated by (198)Au grain implantation alone and 58 were treated by (198)Au implantation in combination with external irradiation. The average (198)Au-grain dose was 70 Gy in 7 days. Gross tumor areas ranged from 2.4 cm(2) to 9 cm(2), and the clinical target areas ranged from 6 cm(2) to 15 cm(2). RESULTS: The follow-up periods ranged from 3 months to 20 years (mean: 5 years 11 months and median: 5 years 1 months). Failure at the site of the primary lesion occurred in 17 patients. Post-treatment mucosal ulceration developed in 15 patients, and all were cured within 25 months by conservative treatment. Osteoradionecrosis was diagnosed in 8 patients, but only one patient required surgical treatment. No severe complications or aggravation of complications developed more than 10 years after treatment. CONCLUSIONS: The results of low-dose-rate (LDR)-brachytherapy (BT) alone and LDR-BT in combination with external irradiation at a total dose of 25 Gy were acceptable from the standpoint of cure rate and QOL. (+info)
Gold marker displacement due to needle insertion during HDR-brachytherapy for treatment of prostate cancer: a prospective cone beam computed tomography and kilovoltage on-board imaging (kV-OBI) study.
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