Infantile fibrosarcoma in the nasal cavity.
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A tumour line inoculated in mice showed high affinity binding for lipoproteins in vitro. Studies in vivo demonstrated that the assimilation of human low density lipoprotein (LDL) by the tumour was very high. Both receptor and non-receptor mediated catabolism of the lipoprotein by the tumour increased as compared to other tissues known to be sites of lipoprotein catabolism (liver, spleen etc.). These findings suggest that lipoproteins may be useful markers for tumours as well as carriers for cytotoxic drugs to target tissues in vivo.
PURPOSE: To investigate the effect of UCN-01 (7-hydroxystaurosporine), a potent and selective protein kinase C inhibitor, on fractionated irradiation or daily chemotherapy; cis-diamminedichloroplatinum(II) (cis-DDP) or 5-fluorouracil (5-FU) in vivo. Radiosensitivity and chemosensitivity given in combination with UCN-01 were further studied in vitro to analyze these in vivo results. METHODS AND MATERIALS: For in vivo studies, single-cell suspension was prepared from fourth generation FSa-II tumors and transplanted subcutaneously into the leg of 8-10-week-old C3Hf/Sed mice. Treatments were initiated when tumors reached an average diameter of 4 mm. Tumor response was studied using tumor growth and growth delay time assays. UCN-01 was given continuously for 7 days using Alzet osmotic pump (4.0 microg/microl/h or approximately 3.2 mg/kg/day). A daily gamma-ray dose of 10 Gy each was given in air for 7 days. Cis-DDP (0.7 mg/kg/day) or 5-FU (20 mg/kg/day) was given by an i.p. injection for 7 days. For in vitro studies, an established FSa-II cell line was used and cell survival was studied by colony formation assay. RESULTS: UCN-01 acted synergistically with fractionated irradiation, though it was slightly radioprotective in vitro and had no effect on SLD repair. The surviving fraction of the FSa-II cells treated with both UCN-01 and cis-DDP in vitro was lower than the calculated additive effect; however, the sensitizing effect of UCN-01 was not found when combined with either of the chemotherapeutic agents in vivo. Possible causes of synergism of combined UCN-01 and fractionated radiation may be that a continuous UCN-01 treatment inhibited clonogen repopulation during the course of fractionated irradiation and accumulated cells in the G2-M phase where cells are most sensitive to irradiation. CONCLUSION: UCN-01 is a promising agent that may indirectly interact with fractionated irradiation in vivo but may not with chemotherapeutic agents.
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BCD-F9 is a murine IgG(2a) monoclonal antibody (mAb) that recognises a conformational epitope found on the surface of many human tumour cells. The aim of this study was to investigate the ability of BCD-F9 to recognise a variety of neoplastic cell lines and to test BCD-F9 in vivo for anticancer activity in subcutaneous (s.c.) and metastatic tumour models. Intravenous (i.v.) administration of BCD-F9 in CD-1 nude mice xenografted s.c. with human HT-1080 cells led to a significant inhibition of tumour growth. We demonstrated that BCD-F9 administrated i.v. significantly prolonged the life-span of CD-1 nude mice inoculated i.v. with the same tumour cell line that induces aggressive lung metastases in the untreated mice. We also investigated the antitumour activity of BCD-F9 in vitro in antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ADCMC) assays. The effector cell subpopulations were obtained by macrophage stimulation (thioglycollate) or natural killer (NK) cell enrichment (negative selection). BCD-F9 was found to be effective in mediating tumour cell killing in vitro by ADCC and ADCMC mechanisms. These results suggest that the mAb BCD-F9 can have a potential use in immunotherapy for treatment of tumours of different origin.
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pH-Dependent variations in the fluorescence intensity of 5-aminolaevulinic acid-induced 5-aminolaevulinic acid protoporphyrin IX (PP IX) were compared with the cell viability following light irradiation. The fluorescence intensity was determined by flow cytometry and the cell activity was investigated by a colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay 24 h after photodynamic treatment. The results obtained by fluorescence measurements clearly showed that pH values of the incubation medium containing (5-ALA) below and above pH 7.4 led to a significant decrease in the fluorescence intensity. The viability of cells incubated with 0.6 mM 5-ALA in a medium at pH 6.0 was unaffected on exposure to light at lambda = 635 nm up to 15 J cm-2. However, cells incubated at pH 7.4 (with the other treatment parameters the same) were nearly completely destroyed. In addition, depletion of intracellular PPIX was faster in physiological medium than in acid medium.
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