Rhabdomyosarcoma Allograft Mouse Model and Treatments

Orthotopic allograft mouse models of rhabdomyosarcoma were generated as described earlier (Aslam et al. 2014 (link)). Once the tumors reached 0.25 cm³, the mice were treated with either entinostat (LC Laboratories) at a daily dose of 10 mg/kg by intraperitoneal injection, actinomycin D (Sigma-Aldrich) at 0.25 mg/kg on day 1 by intraperitoneal injection, a combination of entinostat and actinomycin D, or vehicle (DMSO). Once the tumors reached 1.5 cm³ or the mice became sick (10%–15% loss of body weight) due to drug toxicity, the mice were euthanized. After 5 d of treatment with entinostat, the mice showed signs of drug toxicity (loss of body weight), so the treatment was halted for a day and then continued with 5 mg/kg daily dose (half the initial dose). All of the drug studies in mice were performed after receiving approval from the IACUC at Oregon Health and Science University.

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Abraham J., Nuñez-Álvarez Y., Hettmer S., Carrió E., Chen H.I., Nishijo K., Huang E.T., Prajapati S.I., Walker R.L., Davis S., Rebeles J., Wiebush H., McCleish A.T., Hampton S.T., Bjornson C.R., Brack A.S., Wagers A.J., Rando T.A., Capecchi M.R., Marini F.C., Ehler B.R., Zarzabal L.A., Goros M.W., Michalek J.E., Meltzer P.S., Langenau D.M., LeGallo R.D., Mansoor A., Chen Y., Suelves M., Rubin B.P, & Keller C. (2014). Lineage of origin in rhabdomyosarcoma informs pharmacological response. Genes & Development, 28(14), 1578-1591.

Publication 2014

entinostat actinomycin D

Actinomycin d After treatment Allograft Body Dmso Drug toxicity Entinostat Iacuc Intraperitoneal injection Mice Rhabdomyosarcoma Tumors

Corresponding Organization :

Other organizations : Oregon Health & Science University, Institute of Predictive and Personalized Medicine of Cancer, Harvard Stem Cell Institute, Harvard University, Howard Hughes Medical Institute, Joslin Diabetes Center, Dana-Farber Cancer Institute, The University of Texas Health Science Center at San Antonio, National Cancer Institute, Stanford University, University of Utah, Wake Forest University, Center for Cancer Research, Massachusetts General Hospital, University of Virginia, Cleveland Clinic

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Variable analysis

independent variables

Entinostat (LC Laboratories) at a daily dose of 10 mg/kg by intraperitoneal injection
Actinomycin D (Sigma-Aldrich) at 0.25 mg/kg on day 1 by intraperitoneal injection
A combination of entinostat and actinomycin D
Vehicle (DMSO)

dependent variables

Tumor growth (measured as tumor volume reaching 1.5 cm^3)
Drug toxicity (10%-15% loss of body weight)

control variables

Orthotopic allograft mouse models of rhabdomyosarcoma

controls

Positive control: vehicle (DMSO)
Negative control: Not explicitly mentioned

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