Dose comparison in early estradiol-supported MCF-7 tumors
Animal study · MCF-7 E2 xenografts in ovariectomized athymic CrTac: NCr-Foxn1nu mice; 5 mice bearing 10 tumors per group. [1]
Daily oral brivanib alaninate begun 24 hours after implantation suppressed tumor cross-sectional area at 0.1 mg/g, whereas 0.05 mg/g did not show a significant reduction at six weeks. Tumor blots showed reduced VEGFR-2 Tyr951 phosphorylation without a reported change in total VEGFR-2. Higher-dose tumors also showed increased VEGFA transcription. The molecular response therefore did not establish growth inhibition at the lower dose.
| Endpoint | Reported result | Reference |
|---|---|---|
| Tumor cross-sectional area: 0.1 mg/g plus estradiol versus estradiol vehicle control at 6 weeks | Reported between-group CSA difference −0.37 cm²; p=0.001; α=0.025 | [1] |
| Tumor cross-sectional area: 0.05 mg/g plus estradiol versus estradiol vehicle control at 6 weeks | Reported between-group CSA difference 0.13 cm²; p=0.202; α=0.025; not significant | [1] |
| Tumor VEGFR-2 phosphorylation at Tyr951 and total receptor expression | Qualitative immunoblot result Lower phosphorylation with either brivanib alaninate dose; no reported difference in total VEGFR-2 | [1] |
| Tumor VEGFA mRNA, high-dose brivanib alaninate versus estradiol control | Direction and reported p-value Increased; p=0.02 | [1] |
Conditions shared by the study groups
- Route
- Oral; estradiol supplied by a 0.3 cm subcutaneous silastic capsule.
- Frequency
- Daily, 7 days per week.
- Treatment course
- From 24 hours after implantation; growth followed to 6 weeks.
- Vehicle
- Brivanib alaninate: citric acid buffer, pH 3.5.
| Group / dose | Comparator | Observed result | Reference |
|---|---|---|---|
| Estradiol plus oral vehicle No brivanib alaninate; estradiol capsule. | Reference condition. | Estradiol supported tumor growth. | [1] |
| Lower brivanib alaninate dose 0.05 mg/g body weight plus estradiol. | Estradiol plus oral vehicle. | No significant CSA reduction at 6 weeks (p=0.202). | [1] |
| Higher brivanib alaninate dose 0.1 mg/g body weight plus estradiol. | Estradiol plus oral vehicle. | Lower tumor CSA at 6 weeks (reported difference −0.37 cm²; p=0.001). | [1] |
- Estradiol plus oral vehicle
- Model: Estradiol-supported MCF-7 E2 xenografts in ovariectomized athymic mice; 5 mice and 10 tumors per group.
- Reported limits: No Adooq material or lot validation. Tumors are clustered within mice.
- Lower brivanib alaninate dose
- Model: Estradiol-supported MCF-7 E2 xenografts in ovariectomized athymic mice; 5 mice and 10 tumors per group.
- Reported limits: No Adooq material or lot validation. Tumors are clustered within mice.
- Higher brivanib alaninate dose
- Model: Estradiol-supported MCF-7 E2 xenografts in ovariectomized athymic mice; 5 mice and 10 tumors per group.
- Reported limits: No Adooq material or lot validation. Tumors are clustered within mice.
Methods and source locations
Compound reported in the paper: Brivanib alaninate; Compound label in the paper: BMS 582664
Applies to the reported Bristol Myers Squibb material in mouse tumor experiments; does not validate an Adooq lot.
Methods: Tumor Xenografts, Drug Preparation, Drug Administration, Experiment 2, Western Immunoblotting, RT-PCR, Statistical Analysis; Results: Effects of different doses; Figure 2A–D.
Tumor cross-sectional area: 0.1 mg/g plus estradiol versus estradiol vehicle control at 6 weeks: Weekly caliper-derived CSA; random-effects growth-curve analysis accounting for within-mouse clustering; 5 mice/10 tumors per group. — Results: Effects of different doses of brivanib alaninate in SERM sensitive MCF-7 E2 tumors, first paragraph; Figure 2A and caption.
Tumor cross-sectional area: 0.05 mg/g plus estradiol versus estradiol vehicle control at 6 weeks: Same coherent dose-comparison experiment; the caption rounds p to 0.2. No growth-inhibition claim is assigned to this dose. — Same Results subsection, first paragraph; Figure 2A and caption.
Tumor VEGFR-2 phosphorylation at Tyr951 and total receptor expression: Western immunoblotting of tumor extracts; total receptor, ER/phospho-ER and β-actin panels inspected. No densitometric effect size inferred. — Methods: Western Immunoblotting; Results: Effects of different doses, third paragraph; Figure 2C.
Tumor VEGFA mRNA, high-dose brivanib alaninate versus estradiol control: RT-PCR normalized to 36B4; ΔΔCt; Wilcoxon rank-sum analysis. Figure 2D labels n=4 per group; this is not the 5-mouse growth cohort count. No exact fold value inferred. — Methods: Real time Polymerase Chain Reaction and Statistical Analysis; Results: Effects of different doses, fourth paragraph; Figure 2D and caption.
Estradiol plus oral vehicle · Methods: Drug Preparation, Drug Administration, Experiments 2; Figure 2A and corresponding Results.
Lower brivanib alaninate dose · Methods: Drug Preparation, Drug Administration, Experiments 2; Figure 2A and corresponding Results.
Higher brivanib alaninate dose · Methods: Drug Preparation, Drug Administration, Experiments 2; Figure 2A and corresponding Results.