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    Quantitative molecular monitoring of BCR-ABL and MDR1 transcripts in patients with chronic myeloid leukemia during Imatinib treatment

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    Different mechanisms could sustain Imatinib resistance, including overexpression of MDR1, a gene already known to be responsible for multidrug resistance in other hematologic malignancies. In search for a possible correlation, BCR-ABL and MDR1 expression were measured in 115 serial bone marrow samples from 33 CML patients during Imatinib treatment. All patients achieved complete hematologic responses, and 22 patients also achieved complete cytogenetic responses, with median BCR-ABL mRNA values significantly lower than those observed in the group of cases that were persistently Philadelphia positive. All three cases treated during the accelerated phase showed disease progression after an initial period of remission; all presented either increased levels of BCR-ABL or MDR1 3 months before clinical progression. In the subgroup of cases treated during the chronic phase, BCR-ABL and MDR1 levels were significantly correlated after 3 and 6 months (88 and 80%, respectively) but not after 12 months of treatment (32%). Reported data maintain that MDR1 expression would play an important role in Imatinib resistance when the disease is not fully controlled (e.g., progressive disease or during the first months of treatment)

    Synergistic effects of alpha interferon and 1,25 dihydroxyvitamin D3: Preliminary evidence suggesting that interferon induces expression of the vitamin receptor

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    Background. The active metabolite of vitamin D3-1,25(OH)2D3-is a well-known differentiation inducer. The addition of this metabolite to sensitive cell cultures inhibits proliferation and induces monocytic-macrophagic differentiation. Alpha interferon may also inhibit proliferation and increase the expression of some surface antigens in some neoplastic cells. In the present report, we describe the synergistic activity of these two drugs on U-937 and on cultured cells from a leukemic patient. Methods. Proliferation was studied by H-3-thymidine incorporation; differentiation markers were evaluated immunologically by monoclonal antibodies and by cytochemical tests. Phagocytosis and NBT reduction test were also performed in order to confirm the differentiating properties of these drugs. Finally, the expression of the 1,25(OH)2D3 receptor was evaluated by immunochemical methods. Results. After culturing these cells for 72 hours in the presence of 1,25(OH)2D3, cell proliferation was reduced and the expression of some phenotypic and functional markers suggested monocytic-macrophagic differentiation. Alpha interferon and 1,25(OH)2D3 synergistically inhibit the proliferation of U 937 cells. Alpha interferon increased the expression of the 1,25(OH)2D3 receptor in U-937 cells. Conclusions. The reported results confirm the synergistic activity of INF and 1,25(OH)2D3 on cell proliferation in monoblastic cells. The possible role of the increased expression of the vitamin receptor in cells cultured in the presence of INF is discussed

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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