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Biomedical subjects

M Haber

Publications and source records attributed to M Haber.

131 records · Page 8Linked to original sources

Estimation of vaccine efficacy from epidemics of acute infectious agents under vaccine-related heterogeneity.

A stochastic epidemic model is formulated for the study of the protective effects of vaccination in a population that is stratified by vaccine-related factors. The epidemic model is transformed into a counting process, and then martingale-based methods are used to provide estimators of vaccine efficacy and their variances. Following an example, various extensions of the model are discussed.

Acute Disease↗

Regulation of retinoic acid receptor alpha expression in human neuroblastoma cell lines and tumor tissue.

Human neuroblastoma (NB) cell lines treated with all-trans retinoic acid (RA) differentiate in culture, forming neurites and exhibiting growth arrest. We treated 5 human NB cell lines with RA, and observed a 2-5 fold induction of retinoic acid receptor alpha (RAR alpha) mRNA expression in 4 of the 5 cell lines, as an early cellular response. Induction of RAR alpha expression was specific for RA among several differentiating agents tested. RAR alpha mRNA expression in 13 primary neuroblastoma tumor samples was 3 fold higher in localised compared with advanced tumors (p < 0.05). RAR alpha expression may be necessary for the effects of RA on NB cells in vitro and reduced expression of this gene in vivo may contribute to the process of NB tumorigenesis.

Cell Differentiation↗

Ferritin production and desferrioxamine cytotoxicity in human neuroblastoma cell lines.

In patients with neuroblastoma, elevated serum ferritin is correlated with adverse outcome. In this investigation, three human neuroblastoma cell lines have been characterised in terms of their levels of both intracellular and secreted ferritin and their response to the iron-chelating agent, desferrioxamine (deferoxamine). The cell lines differed markedly in respect of ferritin production as determined by radioimmunoassay. Intracellular and secreted ferritin concentrations for SH-SY5Y and BE(2)-C cells were several fold higher than that determined for IMR-32 cells. IMR-32 cells were most sensitive to desferrioxamine, BE(2)-C intermediate and SH-SY5Y the most resistant to the drug in terms of the respective ID50 values. Combining the differentiating agent retinoic acid with desferrioxamine did not enhance cytotoxicity in the neuroblastoma cells. The present data suggest that neuroblastoma cells secreting a relatively low levels of ferritin may be most responsive to iron chelating agents.

Deferoxamine↗

In vitro effects of MYCN sense and antisense expression in MYCN-amplified human neuroblastoma cells.

Amplification of the MYCN oncogene is a strong predictor of treatment failure and chemo-resistance in childhood neuroblastoma. Stable expression of two partial MYCN gene fragments in antisense orientation reduced Mycn protein expression in an MYCN-amplified neuroblastoma tumor cell line, however, antisense cells did not exhibit an increased in vitro sensitivity to cytotoxic or differentiating agents. In contrast, partial MYCN sense transfectants exhibited increased resistance to cytotoxic drugs. These data suggest that the chemo-resistance of MYCN-amplified neuroblastoma cells is complex, and may be due to factors additional to Mycn protein expression.

Antineoplastic Agents↗