Biomedical subjects

E Solary

Publications and source records attributed to E Solary.

131 records · Page 8Linked to original sources

PubMedDate not supplied

P27KiP1 overexpression inhibits the growth and doxorubicin sensitivity of HT29 human colon cancer cells in vivo.

We have previously shown that p27KiP1 plays a role in the tumor cell resistance of HT29 confluent monolayers to cytotoxic drugs in vitro. To determine whether p27KiP1 was a resistance factor to cytotoxic drugs in vivo we tested the effect of doxorubicin on p27KiP1-overexpressing HT29 tumors in nude mice. In this study we show that ectopic overexpression of p27KiP1 in HT29 human colon cancer cells decreases their tumorigenicity in vivo in nude mice. This decreased tumor growth was associated with increased p27KiP1 protein expression, studied by Western blotting in tumor extracts. Interestingly, the overexpressing-p27KiP1 tumors were significantly more resistant to intraveneous doxorubicin treatment than the control tumors. These results indicate that p27KiP1, which delays tumor growth could also increase tumor resistance to cytotoxic drugs in vivo.

Animals↗

PubMedDate not supplied

Modulation of apoptotic pathways triggered by cytotoxic agents.

Anticancer drugs can induce tumour cell death by apoptosis. The main pathway from specific damage induced by the drug to apoptosis involves activation of caspases in the cytosol by pro-apoptotic molecules such as cytochrome c released from the mitochondria. At least in some cell types, anticancer drugs also upregulate the expression of death receptors and sensitize tumour cells to their cognate ligands, which could be used to amplify the response to cytotoxic drugs. The Bcl-2 family of proteins, which includes anti- and pro-apoptotic molecules, regulates cell sensitivity at the mitochondrial level. Chemotherapeutic drugs modulate their expression (e.g. through p53-dependent gene transcription), their activity (e.g. by phosphorylation) and their subcellular localization (e.g. by translocation of pro-apoptotic proteins from the cytosol to the mitochondria). When interacting with tumour cells, anticancer drugs also activate lipid- and kinase-dependent signalling pathways that modulate the death response to specific damage. Protective pathways include activation of NF kappa B transcription factor, accumulation of heat shock proteins and activation of proteins involved in cell cycle regulation. The recent identification on these pathways to cell death has suggested several new strategies to improve the therapeutic efficacy of currently used anticancer drug regimens.

Antineoplastic Agents↗

PubMedDate not supplied

[Thalidomide with or without dexamethasone for refractory multiple myeloma].

It was shown in 1999 thalidomide could induce a therapeutic response in patients with refractory multiple myeloma. Between March 2000 and January 2002, we treated 21 patients with refractory multiple myeloma with thalidomide (Thalidomide) at initial dose of 400 mg a day. Response rate (Intergroupe Francophone du Myélome criteria) was 33 percent and median progression-free survival estimated to 15 months. All patients suffered from drowsiness and constipation requiring lowest doses. Five patients developed a sensitive neuropathy. Eight refractory patients were treated by a combination of their prior maximally tolerated dose of thalidomide and monthly dexamethasone (Soludécadron) alone (n = 4) or associated to cyclophosphamide (Endoxan) and étoposide (Etopophos) (n = 4). Six patients on 8 were responders. Our results suggest that the combination thalidomide/dexamethasone should be compared to thalidomide alone in a prospective, randomized study in patients with refractory multiple myeloma.

Adult↗

PubMedDate not supplied

Modulation of proliferation, estradiol receptors and estrogen regulated protein PS2/BCEI in human breast cancer cell lines by gamma interferon.

The effects of recombinant gamma interferon (IFN gamma) on proliferation, estrogen-receptor (ER) content, mRNA level and protein secretion of a breast cancer estrogen-induced protein pS2/BCEI were investigated in two human breast cancer cell lines, ZR75-1 and T47D. Both cell lines have estrogen and progesterone receptors and previously showed HLA class I and class II responses to IFN gamma (Int J Cancer 1990; 45: 1169). An antiproliferative effect of IFN gamma (1000-5000 U/ml) was observed in serum containing medium on ZR75-1 but not on T47D cells. Noninhibitory concentration of IFN gamma (100 U/ml) had sensitising antiproliferative effect with antiestrogens on ZR75-1 cells whereas IFN gamma did not modify the growth inhibition observed in T47D cells with antiestrogens. In serum-free, estradiol-free, phenol-red-free chemically defined medium (Cancer Res 1984; 44: 4553), IFN gamma abolished in ZR75-1 but not in T47D the 30% growth stimulation induced by estradiol. In ZR75-1 cells, IFN gamma induced a transitory 30-50% increase of ER content, as measured by ER-enzymoimmunoassay, at day 2 of culture, and reduced mRNA level and secretion of pS2/BCEI. In T47D cells, a 30-50% decrease of ER content was observed but only when cells were long term cultured (30 weeks) with IFN gamma. In this cell line, no transcription of pS2/BCEI was observed. Antiproliferative action of IFN gamma on ZR75-1 cells is associated with an inhibition of estradiol effects and a reduction of pS2/BCEI mRNA level and protein secretion.

Breast Neoplasms↗

PubMedDate not supplied

Multidrug resistance phenotype evaluation by immunofluorescence and functional tests: comparison of two monoclonal antibodies and three fluorescent dyes in three cells lines.

Various agents have been shown to enhance drug sensitivity of multidrug resistant (MDR) cells and are thus of interest when the MDR phenotype is identified. Detection of MDR cells is of importance and can be carried out either by immunofluorescence with monoclonal antibodies or by functional tests using fluorescent dyes uptake. MDR has been analysed by flow cytometry on three sensitive and resistant cell lines, with MRK16 and C219 monoclonal antibodies directed against P-glycoprotein (P-gp) and with rhodamine 123, Hoechst 33342 and daunorubicin. Resistant cells were revealed by MRK16 and C219 but the results obtained with MRK16 gave higher both percentages of fluorescent cells and mean fluorescence. Fluorescence intensity observed with daunorubicin was lower than with rhodamine 123. With Hoechst 33342, mean fluorescence was quite identical on sensitive and on resistant cells. It was concluded that MRK16 and rhodamine 123 were well adapted to detect P-gp and evaluate its functional ability.

ATP Binding Cassette Transporter, Subfamily B, Mem↗