Absence of microsatellite instability in transitional cell carcinoma of the bladder.

OBJECTIVES: To investigate the prevalence of the microsatellite instability related to mismatch repair (MMR) gene defects using a panel of six microsatellite markers, as recommended by a recent workshop on microsatellite instability in colon cancer, because it is still unclear whether abnormalities in DNA MMR genes are involved in transitional cell carcinoma (TCC) of the bladder. METHODS: Three mononucleotide repeats (BAT26, TGFbetaRII, and BAX) were studied in 33 TCC samples and in four bladder cancer cell lines. Three dinucleotide repeats (D2S123, D5S346, and D17S250) were studied in 21 of these 33 TCC samples. RESULTS: No alteration was detected either in the 33 TCC samples analyzed or in the four bladder cancer cell lines (T24, J82, 647V, and 1207) studied. A difference between normal and tumor DNA was observed in only 1 of 21 tumor samples for D17S250. CONCLUSIONS: These data indicate that microsatellite instability is very uncommon in TCC of the bladder.

French multicentric evaluation of mdr1 gene expression by RT-PCR in leukemia and solid tumours. Standardization of RT-PCR and preliminary comparisons between RT-PCR and immunohistochemistry in solid tumours. French Network of the Drug Resistance Intergroup, and Drug Resistance Network of Assistance Publique-Hôpitaux de Paris.

Since there is no consensus on the techniques for multidrug resistance (MDR) phenotype evaluation, many discrepancies concerning the importance and frequency of mdr1 gene expression in leukemias and solid tumors are observed in the literature. In order to establish an inter-laboratory consensus in France, a multicenter study was carried out to propose further guidelines for MDR phenotype evaluation. The techniques used by the 38 laboratories participating in the trial were: immunodetection (immunohisto and/or cytochemistry, flow cytometry), functional tests, reverse transcription-polymerase chain reaction (RT-PCR) or Northern blot. We present the results obtained by 19 laboratories concerning the measurement of mdr1 gene expression assessed by RT-PCR or Northern blot in: (1)19 samples of tumor cells obtained from leukemic patients; (2) six solid tumor samples obtained at surgery; (3) eight cell lines exhibiting variable levels of resistance, and; (4)10 preparations of RNA and of cDNA obtained from solid tumors. Standardization of the RT-PCR technique and preliminary results comparing RT-PCR with immunohistochemistry in solid tumors are also reported.

[Resistance to antineoplastic treatments: mechanisms, clinical value]. / Résistance aux traitements anticancéreux: mécanismes, intérêt clinique.

Drug resistance is a major obstacle to successful chemotherapy for cancer. When it occurs, resistance to a wide range of agents is noted. Factors that rule this resistance can be defined as pharmacologic and cellular. Pharmacologic factors are those that prevent an adequate degree of tumor cell exposure and include considerations of dose and schedule of drugs. Cellular factors are those that imply the tumor cell itself and it is probable that multiple mechanisms co-exists: 1) the drug transport across the tumor cell membrane and the duration of the drug exposure, 2) the drug metabolism (activation, inactivation), 3) the cellular targets and the DNA repair processes. The pleiotropic multidrug resistance (mdr, mrp, lrp), alterations of a target enzyme (topoisomerase II, protein kinase C, glutathione S transferase, O6 alkylguanine-DNA alkyltransferase) and the protein modifications (heat shock protein, metallothioneins) are the principal mechanisms involved. Several methods have been established for the determination of the presence of these drug resistance mechanisms but variations in the results are observed with the different methods used. Therefore, the value and the relative importance of these mechanisms in human tumor resistance is not yet established. In the mean-time, strategies to prevent and to overcome this resistance are developed.