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Strategy for the treatment of acute myelogenous leukemia based on folate receptor β–targeted liposomal doxorubicin combined with receptor induction using.

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Presentation on theme: "Strategy for the treatment of acute myelogenous leukemia based on folate receptor β–targeted liposomal doxorubicin combined with receptor induction using."— Presentation transcript:

1 Strategy for the treatment of acute myelogenous leukemia based on folate receptor β–targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid by Xing Q. Pan, Xuan Zheng, Guangfeng Shi, Huaqing Wang, Manohar Ratnam, and Robert J. Lee Blood Volume 100(2): July 15, 2002 ©2002 by American Society of Hematology

2 Expression and properties of FR-β in peripheral blood granulocytes and in recombinant CHO–FR-β cells.(A) FR-β expression detected in cell lysate by Western blot using anti–FR-β antibody. Expression and properties of FR-β in peripheral blood granulocytes and in recombinant CHO–FR-β cells.(A) FR-β expression detected in cell lysate by Western blot using anti–FR-β antibody. Band intensities were estimated using NIH Image software. (B) Differential sensitivity of FR-β GPI anchors to PI-PLC and nitrous acid; whole cells were treated with PI-PLC, and the cell lysates were analyzed by Western blot using anti–FR-β antibody. Alternatively, cell membranes were treated with nitrous acid and similarly analyzed. (C) Cellular binding of FITC-folate determined by flow cytometry. 10 nM FITC-folate was used with or without preincubation with 1 μM folic acid, as described in “Materials and methods.” Xing Q. Pan et al. Blood 2002;100: ©2002 by American Society of Hematology

3 Fluorescence micrographs of KG-1 cells treated with calcein-containing liposomes.KG-1 cells were incubated with f-L-calcein (A) or L-calcein (B) for 1 hour at 37°C and were washed 3 times with cold PBS. Images of the live cells were collected with a digital... Fluorescence micrographs of KG-1 cells treated with calcein-containing liposomes.KG-1 cells were incubated with f-L-calcein (A) or L-calcein (B) for 1 hour at 37°C and were washed 3 times with cold PBS. Images of the live cells were collected with a digital imaging system, as described in “Materials and methods.” Magnification, × 2000. Xing Q. Pan et al. Blood 2002;100: ©2002 by American Society of Hematology

4 Effect of ATRA on FR-β expression and f-L-calcein uptake in KG-1 cells
Effect of ATRA on FR-β expression and f-L-calcein uptake in KG-1 cells.Cellular FR-β expression was determined by flow cytometry using rabbit anti–FR-β (with normal rabbit IgG as an isotype control) as the primary antibody and FITC-goat anti-rabbit IgG as t... Effect of ATRA on FR-β expression and f-L-calcein uptake in KG-1 cells.Cellular FR-β expression was determined by flow cytometry using rabbit anti–FR-β (with normal rabbit IgG as an isotype control) as the primary antibody and FITC-goat anti-rabbit IgG as the secondary antibody. Liposomal uptake was determined by fluorescence of the encapsulated calcein. (A) FR-β expression in untreated KG-1 cells. (B) FR-β expression in KG-1 cells after a 5-day exposure to ATRA (1 μM). (C) Uptake of f-L-calcein and L-calcein by KG-1 cells and the effect of ATRA. Cells were treated with L-calcein without ATRA pretreatment (1), L-calcein with ATRA pretreatment(2), f-L-calcein without ATRA pretreatment (3), or f-L-calcein with ATRA pretreatment (4). Xing Q. Pan et al. Blood 2002;100: ©2002 by American Society of Hematology

5 Effect of f-L-DOX treatment on the survival of DBA/2 mice carrying L1210JF ascites tumor.DBA/2 mice inoculated intraperitoneally with L1210JF cells were treated with saline, free DOX, L-DOX, or f-L-DOX, as described in “Materials and methods.” Animal surviv... Effect of f-L-DOX treatment on the survival of DBA/2 mice carrying L1210JF ascites tumor.DBA/2 mice inoculated intraperitoneally with L1210JF cells were treated with saline, free DOX, L-DOX, or f-L-DOX, as described in “Materials and methods.” Animal survival was recorded starting from the day of tumor cell inoculation. Xing Q. Pan et al. Blood 2002;100: ©2002 by American Society of Hematology

6 Effect of f-L-DOX treatment on the survival of SCID mice carrying KG-1 ascites tumor.SCID mice inoculated intraperitoneally with KG-1 cells were treated with saline, free DOX, L-DOX, or f-L-DOX, with or without coinjection of ATRA, as described in “Material... Effect of f-L-DOX treatment on the survival of SCID mice carrying KG-1 ascites tumor.SCID mice inoculated intraperitoneally with KG-1 cells were treated with saline, free DOX, L-DOX, or f-L-DOX, with or without coinjection of ATRA, as described in “Materials and methods.” Animal survival was recorded starting from the day of tumor cell inoculation. Xing Q. Pan et al. Blood 2002;100: ©2002 by American Society of Hematology


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