Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Nestr. : il. ; 32 cm
Projekt sleduje mechanismus prevence IDDM BCG vakcínou. Současně využívá tohoto modelu pro hledání alelických forem lidského Nramp-u , genu kódujícího přirozenou rezistenci hostitele na některé intracelulární infekce.
- MeSH
- Autoantigens adverse effects classification MeSH
- BCG Vaccine therapeutic use MeSH
- Diabetes Mellitus, Type 1 genetics immunology prevention & control MeSH
- Enzyme-Linked Immunosorbent Assay utilization methods MeSH
- Mycobacterium bovis genetics immunology MeSH
- Mycobacterium Infections MeSH
- Conspectus
- Lékařské vědy. Lékařství
- NML Fields
- alergologie a imunologie
- vnitřní lékařství
- NML Publication type
- závěrečné zprávy o řešení grantu IGA MZ ČR
This study was designed to compare the antileukemic activity of prednisolone and dexamethasone in childhood acute lymphoblastic leukemia (ALL) under in vitro conditions. The chemoresistance of leukemic cells was ascertained by means of a MTT assay in 69 ALL children at diagnosis and the concentration killing 50% of leukemic cells (LCS50) was determined. The children were treated using the protocol ALL-BFM 90/95. Statistical correlations were made among prednisolone (PRED) and/or dexamethasone (DEX) LCS50 and absolute number of blast cells (ANB) on day 0/8 and a new parameter named blast cells clearance (BCC, BCC8 [%] = ANB8: ANB0 x 100) on day 8. Despite the previously published results of Ito et al. (J. Clin. Oncol. 14: 2370-2376, 1996) and Kaspers et al. (MPO 27: 114-121, 1996) on a positive correlation of DEX versus PRED LCS50 (p < 0.002), in our study, we identified 30% of children (21/69) with differential in vitro responsiveness to PRED and DEX. 16% of patients (11/69) were highly sensitive to DEX and resistant to PRED, while 14% of them (10/69) were resistant to DEX and highly sensitive to PRED. The major difference found in our and the other studies was in the processing of leukemic cells. These results were confirmed in a model experiment using the CCRF-CEM line, where we showed that sensitivity to PRED and DEX, but not to other anti-cancer drugs critically depends on manipulation with tumor cells (cryopreservation). Correlation of PRED/DEX in vitro sensitivity values with parameters of in vivo patient's response to PRED monotherapy identified significant association of PRED LCS50 with BCC8 (p < 0.02). It indicates strong linkage of in vitro sensitivity to PRED with percentage of blast cells eliminated from patient blood within the first 8 days of PRED monotherapy.
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma blood pathology MeSH
- Blast Crisis MeSH
- Cell Line MeSH
- Drug Resistance, Neoplasm MeSH
- Dexamethasone toxicity MeSH
- Child MeSH
- Bone Marrow pathology MeSH
- Humans MeSH
- Adolescent MeSH
- Tumor Cells, Cultured MeSH
- Prednisolone toxicity MeSH
- Antineoplastic Agents toxicity MeSH
- Drug Screening Assays, Antitumor MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
