All in vivo efficacy studies were approved by Genentech's Institutional Animal Care and Use Committee (IACUC) and adhered to the ILAR Guide for the Care and Use of Laboratory Animals. Nine to fourteen week-old female C.B-17 SCID beige mice (Charles River Laboratories) were inoculated subcutaneously with either 5 million NCI-H460 or 5 million NCI-H460 S156Y cells suspended in a 1∶1 ratio of HBSS and phenol red-free matrigel (BD Biosciences). Mice with similarly sized tumors (mean volume 200–300 mm3) were randomized into treatment cohorts. Mice were dosed for daily (QD) 7 days, orally, with vehicle [PEG400/H2O/EtOH (60/30/10; vol/vol/vol)] or GNE-618. Tumor sizes and body weights were recorded twice weekly. Tumors were measured using digital calipers and volumes were calculated using the formula lw2×0.5 and reported as mean tumor volume ± SEM. Mice with tumor volumes ≥2000 mm3 or with losses in body weight ≥20% from their weight at the start of treatment were euthanized per IACUC guidelines. Percent tumor growth inhibition (TGI) was calculated using the formula [(mean tumor volumevehicle − mean tumor volumetreatment) ÷ mean tumor volumevehicle] ×100. Student's t-test was used to calculate significance in anti-tumor response between drug and vehicle treated mice.
Cb 17 scid beige mice
Manufactured by Charles River Laboratories
The CB-17 SCID-beige mouse is a laboratory animal model that exhibits a severe combined immunodeficiency (SCID) phenotype and a beige coat color mutation. The SCID mutation results in a lack of functional T and B cells, while the beige mutation affects melanocyte function, leading to the distinct coat color. This animal model is commonly used in biomedical research, particularly in the areas of immunology, oncology, and transplantation studies.
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3 protocols using cb 17 scid beige mice
1
In Vivo Efficacy of GNE-618 in NSCLC Xenografts
2
Xenograft Mouse Model of SCLC
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CB-17 SCID-beige mice aged 5–6 weeks were purchased from the Charles River Laboratories (Wilmington, MA). H146 cells at a concentration of 5×106 per mouse in 50% Matrigel (Cat. No. 356237, Corning, Corning, NY) mixed with 50% serum/antibiotic-free RPMI medium were injected subcutaneously (s.c.) into the right flank region of the mice as described previously.(26 (link), 32 (link)) Tumor size was measured twice a week with digital calipers and tumor volume was calculated using the formula (Length×Width2×0.5). The mice were randomized into different treatment groups when the tumors reached ~150 mm3 (for tumor inhibition study) or ~500 mm3 (for tumor regression study). Mice were treated with vehicle, 753b (5 mg/kg, once a week or every four days, i.p.), or DT2216 (15 mg/kg, once a week, i.p.). DT2216 and 753b were formulated in 50% phosal 50 PG, 45% miglyol 810N and 5% polysorbate 80. Post-euthanasia, the tumors were harvested, lysed, and used for immunoblotting analysis. All the animal experiments were performed in accordance with the IACUC policies.
3
Xenograft Mouse Model of SCLC
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+ Expand
CB-17 SCID-beige mice aged 5–6 weeks were purchased from the Charles River Laboratories (Wilmington, MA). H146 cells at a concentration of 5×106 per mouse in 50% Matrigel (Cat. No. 356237, Corning, Corning, NY) mixed with 50% serum/antibiotic-free RPMI medium were injected subcutaneously (s.c.) into the right flank region of the mice as described previously.(26 (link), 32 (link)) Tumor size was measured twice a week with digital calipers and tumor volume was calculated using the formula (Length×Width2×0.5). The mice were randomized into different treatment groups when the tumors reached ~150 mm3 (for tumor inhibition study) or ~500 mm3 (for tumor regression study). Mice were treated with vehicle, 753b (5 mg/kg, once a week or every four days, i.p.), or DT2216 (15 mg/kg, once a week, i.p.). DT2216 and 753b were formulated in 50% phosal 50 PG, 45% miglyol 810N and 5% polysorbate 80. Post-euthanasia, the tumors were harvested, lysed, and used for immunoblotting analysis. All the animal experiments were performed in accordance with the IACUC policies.
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