l 744 832  (Abgenix Inc)

Journal: Molecular Cancer

Article Title: Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

doi: 10.1186/1476-4598-7-39

Figure Lengend Snippet: Proliferation of mouse lymphocytes and lymphoma cells in vitro in the presence and absence of L-744,832 . Splenocytes were harvested from either a BCR HEL transgenic mouse (panels a - e ) or a moribund Eμ- Myc /BCR HEL /HEL transgenic mouse (panels f - j ). The splenocytes were depleted of T cells and labeled with CFSE. Cells were cultured in RPMI (panels a , f - j ) or RPMI with 2 μg/ml anti-IgM and 1 μg/ml anti-CD40 (panels b - e ) and 0 – 40 μM L-744,832 were included in the culture media, as indicated. After three days, cellular proliferation was measured by flow cytometry. Cells that have proliferated measure less than 10 3 fluorescence units. For comparison, panels c, d , and e show proliferation in the absence of L-744,832 as a black line.

Article Snippet: Cells were then placed in culture at 37°C in 5% CO 2 at 5 × 10 5 cells/ml in complete RPMI with 2 μg/ml goat anti- mouse IgM, μ-specific (Jackson Immunoresearch, West Grove, PA), 1 μg/ml anti-mouse CD40 (BD Biosciences, San Diego, CA), and L-744,832, as indicated.

Techniques: In Vitro, Transgenic Assay, Labeling, Cell Culture, Flow Cytometry, Fluorescence

Journal: Molecular Cancer

Article Title: Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

doi: 10.1186/1476-4598-7-39

Figure Lengend Snippet: Treatment of lymphoma-bearing mice with L-744,832 . A . L-744,832 treatment prevents the B cell lymphoma from becoming established. Unmanipulated C57BL/6 mice (Wild-type) or mice transplanted with 10 6 Eμ- Myc/ BCR HEL /HEL transgenic lymphoma cells (Transplant recipient) were injected intravenously with 625 μg L-744,832 in 0.25 ml PBS daily (light bars) or left untreated (black bars). After 28 days, mice were euthanized and the spleens were dissected and viable cell counts of splenocytes resuspended in RPMI were determined using a hemocytometer. Error bars represent the standard deviation calculated for all mice in each group (n = 4). B and C . L-744,832 treatment causes rapid regression of lymphomas. In a separate experiment, mice transplanted with transgenic tumor cells were allowed to develop tumors for 20 or 24 days before daily treatment with L-744,832 as above for either 7 days (L744 × 7) or 3 days (L744 × 3), respectively. Twenty eight days following the tumor transplantation the mice were euthanized. Spleens were removed from tumor recipient mice and C57BL/6 control mice and photographed. Single cell suspensions from the spleens of mice that were left untreated (black bars), treated for the final 7 days (shaded bars), or treated for the final 3 days (clear bars) were counted using a hemocytometer. Data shown are the average of 4 mice in each group and error bars represent the standard deviation.

Article Snippet: Cells were then placed in culture at 37°C in 5% CO 2 at 5 × 10 5 cells/ml in complete RPMI with 2 μg/ml goat anti- mouse IgM, μ-specific (Jackson Immunoresearch, West Grove, PA), 1 μg/ml anti-mouse CD40 (BD Biosciences, San Diego, CA), and L-744,832, as indicated.

Techniques: Transgenic Assay, Injection, Standard Deviation, Transplantation Assay

Journal: Molecular Cancer

Article Title: Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

doi: 10.1186/1476-4598-7-39

Figure Lengend Snippet: Flow cytometry of isolated cells from mice treated with L-744,832 . Relative numbers of B- and T-cells were measured from unmanipulated C57BL/6 mice ( A ) or C57BL/6 mice that had received transgenic lymphoma transplants 28 days previously ( B ). The mice were left untreated or treated with L-744,832 for 28 days (L744 × 28) or for the final 7 days (L744 × 7). The numbers of B cells (upper left quadrant) and T cells (lower right quadrant) isolated from lymph nodes (first column), spleen (second column), or thymus (third column) were determined by flow cytometry after staining with antibodies to B220 and Thy1.2. The mean percentage and standard deviation of the B220 + and the Thy1.2 + cells are shown in the appropriate quadrant of each plot. There were 4 mice in all groups, except the L744 × 28 wild-type group, which had 2 mice.

Article Snippet: Cells were then placed in culture at 37°C in 5% CO 2 at 5 × 10 5 cells/ml in complete RPMI with 2 μg/ml goat anti- mouse IgM, μ-specific (Jackson Immunoresearch, West Grove, PA), 1 μg/ml anti-mouse CD40 (BD Biosciences, San Diego, CA), and L-744,832, as indicated.

Techniques: Flow Cytometry, Isolation, Transgenic Assay, Staining, Standard Deviation

Journal: Molecular Cancer

Article Title: Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

doi: 10.1186/1476-4598-7-39

Figure Lengend Snippet: Tumor presence in bone marrow is blocked by L-744,832 . The presence of IgM a positive transgenic lymphoma cells in the bone marrow was measured using flow cytometry. C57BL/6 mice were transplanted with 10 6 tumor cells from an Eμ- Myc /BCR HEL /HEL mouse (panels b - d ) or left unmanipulated (panel a ). Transplant recipient mice were left untreated (panel b ) or treated with L-744,832 for either 28 days (panel c ) or for the final 7 days of the experiment (panel d ). Bone marrow was harvested from the femurs and tibias of wild-type mice (panel a ), untreated tumor recipient mice (panel b ), 28-day treated tumor recipient mice (panel c ) or 7-day treated tumor recipient mice (panel d ). Isolated cells were stained for IgM a and analyzed by flow cytometry. The mean percentage and standard deviation of IgM a positive cells are indicated above each histogram for 4 mice in each treatment group.

Article Snippet: Cells were then placed in culture at 37°C in 5% CO 2 at 5 × 10 5 cells/ml in complete RPMI with 2 μg/ml goat anti- mouse IgM, μ-specific (Jackson Immunoresearch, West Grove, PA), 1 μg/ml anti-mouse CD40 (BD Biosciences, San Diego, CA), and L-744,832, as indicated.

Techniques: Transgenic Assay, Flow Cytometry, Isolation, Staining, Standard Deviation

Journal: Molecular Cancer

Article Title: Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

doi: 10.1186/1476-4598-7-39

Figure Lengend Snippet: Long-term remission and regression of lymphomas after L-744,832 treatment . In two separate experiments (panels A and B ) mice transplanted with transgenic lymphoma cells were treated for 7 days with L-744,832 starting 21 days after transplantation (blue line) or left untreated (red line). In the first experiment (panel A), 5 mice each were treated with L-744,832 or left untreated. In the second experiment (panel B), 10 mice were treated with L-744,832 and 5 mice were untreated. Mice were then monitored for signs of lymphadenopathy and euthanized when moribund.

Article Snippet: Cells were then placed in culture at 37°C in 5% CO 2 at 5 × 10 5 cells/ml in complete RPMI with 2 μg/ml goat anti- mouse IgM, μ-specific (Jackson Immunoresearch, West Grove, PA), 1 μg/ml anti-mouse CD40 (BD Biosciences, San Diego, CA), and L-744,832, as indicated.

Techniques: Transgenic Assay, Transplantation Assay