Characteristics of novel myeloid precursor cell line, PC-MDS, established from a bone marrow of the patient with therapy-related myelodysplastic syndrome.

We report on characteristics of the first human cell line, PC-MDS, derived from a bone marrow of a patient with therapy-related myelodysplastic syndrome (t-MDS) who had no overt post-MDS leukemia. Classic cytology analyses, immunophenotyping, cytogenetic and molecular genetic procedures were used for characterization of the cell line. PC-MDS cells are positive for the expression of CD13, CD15, CD30, CD33, and CD45 antigen. Positive cytochemical staining and immunophenotype analyses indicated that PC-MDS cells have some characteristics of the early myeloid precursor cell. The karyotype analysis of PC-MDS cell line revealed various numerical and structural changes including those typically associated with t-MDS: del(5)(q13)[7], der(5)t(5;11)(p11;q11)[13], -7[6], del(7)(q31)[2], +20[3], -20[4]. Evaluation of methylation status in a promoter region of p15, p16 and MGMT genes showed biallelic hypermethylation pattern of 5' promoter region only in MGMT gene. PC-MDS is the first t-MDS derived cell line, and based on its immunological, cytogenetic and molecular characterization could be a new tool in evaluation of complex biology of MDS and a model for methylation studies.

Modulation of TNF-alpha activity in tumor PC cells using anti-CD45 and anti-CD95 monoclonal antibodies.

TNF-alpha is a pleiotropic cytokine produced by activated T-cytotoxic lymphocytes and NK cells that is involved in signal transduction after interacting with the appropriate cell surface receptors. The modulation of signals by TNF-alpha receptor super-family is involved in the regulation of cell activation, proliferation, differentiation and control of the cell survival including cell death by apoptosis and necrosis. We have monitored the kinetics of apoptosis/necrosis on PC cells, after TNF-alpha exposure of pre-treated cells to anti-CD95 and anti-CD45 monoclonal antibodies. The results showed that in comparison with untreated cells, TNF-alpha, after 6-24 h of incubation significantly increased apoptosis and necrosis in PC cells. These effects were significantly different in comparison to both untreated cells and cells pre-treated with anti-CD45 monoclonal antibodies. However, TNF-alpha on PC cells pre-treated with anti-CD95 monoclonal antibody significantly decreased apoptotic and necrotic form of cell death. We concluded that anti-CD45 and CD95 monoclonal antibodies modulates the effect of TNF-alpha on this cell line in vitro, and that these molecules participate in TNF-alpha cytotoxic response.

Growth Effects of Some Platinum(II) Complexes with Sulfur-Containing Carrier Ligands on MCF7 Human Breast Cancer Cell Line upon Simultaneous Administration with Taxol.

The platinum (II)complexes, cis-[PtCl(2)(CH(3)SCH(2)CH(2)SCH(3))] (Pt1), cis-[PtCl(2)(dmso)(2)] (dmso is dimethylsulfoxide; Pt2) and cis-[PtCl(2)(NH(3))(2)] (cisplatin), and taxol (T) have been tested at different equimolar concentrations. Cells were exposed to complexes for 2 h and left to recover in fresh medium for 24, 48 or 72 h. Growth inhibition was measured by tetrazolium WST1 assay Analyses of the cell cycle, and apoptosis were performed by flow cytometry, at the same exposure times. The IC50 value of each platinum(II) complex as well as combination index (CI; platinum(II) complex + taxol) for various cytotoxicity levels were determined by median effects analysis.MCF7 cells were found to be sensitive to both Pt1 and Pt2 complexe These cisplatin analogues influenced the cell growth more effectively as compared to cisplatin. Cytotoxic effect was concentration and time-dependent. Profound growth inhibitory effect was observed for Pt1 complex, across all its concentrations at all recovery periods. A plateau effect was achieved three days after treatment at Pt1 concentrations