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Biomedical subjects

E Leone

Publications and source records attributed to E Leone.

47 records · Page 3Linked to original sources

The strategy.

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Case Management↗

Tumor-specific dose scheduling of bimodal radioimmunotherapy and chemotherapy.

INTRODUCTION: Radioimmunotherapy (RAIT) has been shown to enhance the efficacy of chemotherapy in a variety of tumor models. When multiple drugs are available for a given tumor type, several questions arise, such as how one selects the appropriate drug to be used with RAIT, in what sequence to administer the two therapeutic agents and how to space the two modalities. Unique molecular characteristics affecting chemo- and radiosensitivity are found in every tumor. We postulated that the agents and dose scheduling of bimodal RAIT plus chemotherapy might have to be tailored to each tumor based on the expression of specific relevant genes. MATERIALS AND METHODS: To determine whether a single choice of agents and sequence and spacing of agents would be effective in 4 established human ovarian cancer cell lines, the cytotoxic effect of four standard first- and second-line chemotherapeutic agents used to treat ovarian cancer (doxorubicin, carboplatin, paclitaxel, or topotecan) or radioimmunotherapy (90Y-RS-7 IgG anti-EGP1) were evaluated as single agents or as a bimodal therapy. The four human ovarian cancer lines differed with respect to expression of p53 and drug resistance proteins: SKOV3 (p53null, mdr-, mrp+), A2780 (p53wt, mdr+, mrp), IGROV-1 (p53mut, mdr, mrp+), and OVCAR3 (p53mut, mdr-, mrp-). RESULTS: The profile of chemo- and radiosensitivity for the 4 drugs and for RAIT was unique for each of the four tumor lines. As a result, combinations of radio-antibody and chemotherapy that resulted in good growth inhibition in one tumor line were ineffective in another. Several specific synergistic and antagonistic combinations were identified for each of the ovarian cancer cell lines studied. CONCLUSION: These studies provide evidence that individualized bimodal RAIT and chemotherapy has to be used for each tumor. Therefore, the influence of individual molecular traits on growth inhibition effects from different combinations of agents needs to be studied. This work should then permit rational choices of which drug to add to RAIT, which dose-schedule to use (sequential with RAIT first or sequential with drug first) and how to space the two modalities, based on certain phenotypic markers of the tumors.

Antineoplastic Agents↗

Poly(ADP-ribose)synthetase from HeLa cell nuclei: purification and properties.

Poly(ADP-ribose)synthetase has been purified over 600-fold from HeLa cell nuclei. Upon electrophoresis on 9% polyacrylamide slab-gel in the presence of SDS, the purified enzyme resolved in two bands that showed similar apparent Mr values, 110,000 and 118,000. The aminoacid composition of the two components differed from compositions reported for the same enzyme from other sources. In accordance with other reports, the enzyme purified from HeLa cell nuclei exhibited an absolute dependence on DNA and its activity was modulated by changes in the histone concentration. Incubation of intact nuclei from HeLa cells with [14C]NAD resulted in the isolation of a poly(ADP-ribose)synthetase to which a definite radioactivity is bound. These results are taken as a further demonstration that the enzyme can be auto-ADP-ribosylated.

Adenosine Diphosphate Ribose↗

Main properties of ox kidney uricase.

The main properties of ox kidney uricase have been characterized. Optimum pH and temperature, molecular weight, isoelectric point and u.v. absorption spectrum have been determined, and the behaviour with inhibitors, as well as with antibodies, has been studied. The enzyme is very similar to pig liver uricase, so that the possibility of their complete identity must be taken in consideration.

Animals↗