SCID Mice

Example 23

We have demonstrated that LXR agonists inhibit in vitro cancer progression phenotypes in breast cancer, pancreatic cancer, and renal cancer. To investigate if LXR agonist treatment inhibits breast cancer primary tumor growth in vivo, mice injected with MDA-468 human breast cancer cells were treated with either a control diet or a diet supplemented with LXR agonist GW3965 2 (FIG. 36).

To determine the effect of orally delivered GW3965 2 on breast cancer tumor growth, 2×106 MDA-468 human breast cancer cells were resuspended in 50 μL PBS and 50 μL matrigel and the cell suspension was injected into both lower memory fat pads of 7-week-old Nod Scid gamma female mice. The mice were assigned to a control diet treatment or a GW3965-supplemented diet treatment (75 mg/kg/day) two days prior to injection of the cancer cells. The GW3965 2 drug compound was formulated in the mouse chow by Research Diets, Inc. Tumor dimensions were measured using digital calipers, and tumor volume was calculated as (small diameter)²×(large diameter)/2.

Treatment with GW3965 resulted in significant reduction in breast cancer tumor size in vivo (FIG. 36).

Example 42

The efficacy of cAC10 conjugates were evaluated in admixed Karpas/KarpasBVR (Hodgkin lymphoma) xenografts. Conjugates with an average of 4 drug moieties per antibody were used. The admixed tumor model was implanted subcutaneously into SCID mice with a mixture containing Karpas 299 (2.5×10⁶ cells per mouse) and KarpasBVR (5×10⁶ cells per mouse). Treatment was initiated when the average tumor size reached at least 100 mm³ for tumor efficacy studies. Tumor volumes are calculated using the formula (0.5×L×W²) where L and W are the longer and shorter of two bidirectional measurements.

Example 51

The NOD SCID gamma mouse model of chronic, asymptomatic C. parvum infection was used to test in vivo compound efficacy. NOD SCID gamma mice were infected with ˜1×10⁵ C. parvum oocysts by oral gavage 5-7 days after weaning. The infected animals begin shedding oocysts in the feces 1 week after infection, which is measured by quantitative PCR (qPCR). Based on experience with the positive control compound paromomycin, four mice are required per experimental group to achieve 80% power to detect an 80% percent reduction in parasite shedding after four days of drug compound. In additional to the experimental drug regimen groups, additional negative (gavage with DMSO/methylcellulose carrier) and positive (paromomycin 2000 mg/kg once daily) control groups are included in each experiment. Mice are infected 5-7 days after weaning (day −6), infection is confirmed 1 week later (day 0), and experimental compounds are dosed by oral gavage on days 1-4. The dosing frequency was as indicated. Treatment efficacy was assessed by measurement of fecal oocyst shedding by qPCR on day 5.