Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice-10

for neutrophils (A and B), lymphocytes (C and D) and monocytes (E and F). Pre-radiation blood values reflect an average of all animals in both groups (70 mice) before radiation and tumor inoculation. The normal threshold values for neutrophil, lymphocyte and monocyte counts in C57BL/6 mice are indicated. Following the initial dose of vehicle or cytokine, 4 subsequent doses were given every 3–4 days following radiation. IL-12 treated mice received a total dose (5 single doses) of 220 ng, whereas G-CSF treated mice received a total dose (5 single doses) of 5 μg.<p><b>Copyright information:</b></p><p>Taken from "Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice"</p><p>http://www.translational-medicine.com/content/6/1/26</p><p>Journal of Translational Medicine 2008;6():26-26.</p><p>Published online 19 May 2008</p><p>PMCID:PMC2424034.</p><p></p

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice-7

Odel (B). IL-12 treatment significantly reduces tumor growth following cyclophosphamide treatment in late stage tumor models. In the EL4 tumor model, treatment with IL-12 pre-post or IL-12 post-only significantly reduced tumor growth (%T/C < 50%), as compared to both the G-CSF vehicle control groups at the end point of tumor growth assessments. In the Lewis lung cancer model, the IL-12 pre-post and IL-12 pre-only treatment groups yielded a significant reduction in tumor growth (%T/C < 50%), as compared to both the G-CSF and vehicle control groups at the end point of tumor growth assessments. These tumor models represent a late stage cancers, as compared with the models used for the radiation studies because tumors were apparent at the start of the treatments consisting of cyclophosphamide and cytokine therapy. In the case of the lymphoma model, therapy was initiated when the tumors were very large (about 500 mm).<p><b>Copyright information:</b></p><p>Taken from "Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice"</p><p>http://www.translational-medicine.com/content/6/1/26</p><p>Journal of Translational Medicine 2008;6():26-26.</p><p>Published online 19 May 2008</p><p>PMCID:PMC2424034.</p><p></p

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice-1

S reflect an average of all animals in both groups (70 mice) before radiation and tumor inoculation. The normal threshold value for murine red blood cell counts is indicated. Following the initial dose of vehicle or cytokine, 4 subsequent doses were given every 3–4 days following radiation. IL-12 treated mice received a total dose (5 single doses) of 220 ng, whereas G-CSF treated mice received a total dose (5 single doses) of 5 μg.<p><b>Copyright information:</b></p><p>Taken from "Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice"</p><p>http://www.translational-medicine.com/content/6/1/26</p><p>Journal of Translational Medicine 2008;6():26-26.</p><p>Published online 19 May 2008</p><p>PMCID:PMC2424034.</p><p></p

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice-0

) for neutrophils (A and B), lymphocytes (C and D) and monocytes (E and F). Pre-radiation blood values reflect an average of all animals in both groups (70 mice) before radiation and tumor inoculation. The normal threshold values for neutrophil, lymphocyte and monocyte counts in C57BL/6 mice are indicated. Following the initial dose of vehicle or cytokine, 4 subsequent doses were given every 3–4 days following radiation. IL-12 treated mice received a total dose (5 single doses) of 220 ng, whereas G-CSF treated mice received a total dose (5 single doses) of 5 μg.<p><b>Copyright information:</b></p><p>Taken from "Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice"</p><p>http://www.translational-medicine.com/content/6/1/26</p><p>Journal of Translational Medicine 2008;6():26-26.</p><p>Published online 19 May 2008</p><p>PMCID:PMC2424034.</p><p></p

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice-6

Eflect an average of all animals in both groups (80 mice) before cyclophosphamide and tumor inoculation. The normal threshold value for murine platelet counts is indicated. EL4 mice received a cyclophosphamide dose of 250 mg/kg and the LL mice received a cyclophosphamide dose of 225 mg/kg. IL-12 treated mice received a total dose of 50 ng (pre-only) and 150 ng (post-only and pre-post (pre-post dose was split 50 ng before and 100 ng after cyclophosphamide)), whereas G-CSF treated mice received a total dose 1.5 μg.<p><b>Copyright information:</b></p><p>Taken from "Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice"</p><p>http://www.translational-medicine.com/content/6/1/26</p><p>Journal of Translational Medicine 2008;6():26-26.</p><p>Published online 19 May 2008</p><p>PMCID:PMC2424034.</p><p></p

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice-11

reflect an average of all animals in both groups (70 mice) before radiation and tumor inoculation. The normal threshold value for murine red blood cell counts is indicated. Following the initial dose of vehicle or cytokine, 4 subsequent doses were given every 3–4 days following radiation. IL-12 treated mice received a total dose (5 single doses) of 220 ng, whereas G-CSF treated mice received a total dose (5 single doses) of 5 μg.<p><b>Copyright information:</b></p><p>Taken from "Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice"</p><p>http://www.translational-medicine.com/content/6/1/26</p><p>Journal of Translational Medicine 2008;6():26-26.</p><p>Published online 19 May 2008</p><p>PMCID:PMC2424034.</p><p></p

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice-2

Ect an average of all animals in both groups (70 mice) before radiation and tumor inoculation. The normal threshold value for murine platelet counts is indicated. Following the initial dose of vehicle or cytokine, 4 subsequent doses were given every 3–4 days following radiation. IL-12 treated mice received a total dose (5 single doses) of 220 ng, whereas G-CSF treated mice received a total dose (5 single doses) of 5 μg.<p><b>Copyright information:</b></p><p>Taken from "Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice"</p><p>http://www.translational-medicine.com/content/6/1/26</p><p>Journal of Translational Medicine 2008;6():26-26.</p><p>Published online 19 May 2008</p><p>PMCID:PMC2424034.</p><p></p

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice-5

Lues reflect an average of all animals in both groups (80 mice) before cyclophosphamide and tumor inoculation. The normal threshold value for murine red blood cell counts is indicated. EL4 mice received a cyclophosphamide dose of 250 mg/kg and the LL mice received a cyclophosphamide dose of 225 mg/kg. IL-12 treated mice received a total dose of 50 ng (pre-only) and 150 ng (post-only and pre-post (pre-post dose was split 50 ng before and 100 ng after cyclophosphamide)), whereas G-CSF treated mice received a total dose 1.5 μg.<p><b>Copyright information:</b></p><p>Taken from "Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice"</p><p>http://www.translational-medicine.com/content/6/1/26</p><p>Journal of Translational Medicine 2008;6():26-26.</p><p>Published online 19 May 2008</p><p>PMCID:PMC2424034.</p><p></p

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice-3

Odel (B). Mice in both tumor models were given 625 rad at day 1. Mice in the EL4 lymphoma tumor model were given a second dose of radiation on day 22 (560 rad), and mice in the Lewis Lung cancer tumor model also were given a second dose of radiation on day 22 (750 rad) following the initial radiation dose. Tumor measurements were made on the days indicated by measuring the tumor diameter and converting this measurement into tumor volume using a spherical volume formula. In the EL4 lymphoma model, all IL-12 treatment groups significantly reduced tumor growth (%T/C < 50%) as compared with the PBS and G-CSF controls at the end point of tumor volume evaluation. In the Lewis lung cancer model, only the IL-12 post-only treatment group gave a significant reduction in tumor growth (%T/C < 50%) at the end point of tumor volume evaluation. The change in the slope of the curve for days 19–23 as compared to days 23–27, which occurs after the second radiation, may indicate a radio-sensitizing effect of the indicated treatments.<p><b>Copyright information:</b></p><p>Taken from "Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice"</p><p>http://www.translational-medicine.com/content/6/1/26</p><p>Journal of Translational Medicine 2008;6():26-26.</p><p>Published online 19 May 2008</p><p>PMCID:PMC2424034.</p><p></p

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice-9

left), G-CSF (top, middle) and IL-12 pre-post (top, right) are shown. For the Lewis lung cancer model (bottom), vehicle (bottom, left) and IL-12 pre-only (bottom, middle) are shown. No G-CSF treated mice survived the second radiation dose. A normal (untreated) control bone marrow specimen is also shown (bottom, right).<p><b>Copyright information:</b></p><p>Taken from "Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice"</p><p>http://www.translational-medicine.com/content/6/1/26</p><p>Journal of Translational Medicine 2008;6():26-26.</p><p>Published online 19 May 2008</p><p>PMCID:PMC2424034.</p><p></p