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Human Xenograft Models Introduction Mouse models of cancer have consistently been used to determine the in vivo activity of new anti-cancer therapeutics prior to clinical development and testing in humans. The most common models are xenografts of human tumors and cell lines grown subcutaneously in immunodeficient mice such as athymic (nude) or severe combined immune deficient (SCID) mice. These mouse strains exhibit very high take rates for xenografts, making them ideal hosts for in vivo propagation of human tumor cells. Xenograft tumors are usually established via subcutaneous inoculation of a predetermined number of tumor cells into the flank of nude mice. Xenograft models are commonly used to determine ideal drug dosing, treatment schedules, and routes of drug administration that maximize anti-tumor efficacy and therapeutic window. The following are a few examples of cancer xenograft models performed by Noble Life Sciences. Antitumor Activity of Gemcitabine in the ASPC-1 Xenograft Protocol Human Pancreatic Cancer Xenograft Model Human cancer cells were injected subcutaneously into the right flank of 8 week old female NU NU nude mice (Crl:NU-Foxn1nu): 4000 ) ASPC-1 human pancreatic cancer cells HCT-116 human colon cancer cells A549 lung cancer cells SKOV-3 ovarian cancer cells Vehicle Control Gemcitabine 100 mg/kg IP Days 12, 19, & 26 3 Tumor Volume (mm Antitumor Activity of Gemcitabine in the ASPC-1 Human Pancreatic Cancer Xenograft Model 3000 2000 1000 0 Tumor size measurements were initiated 8 days post inoculation and monitored three times per week. Tumor measurements were evaluated using calipers; tumor size was calculated using the 2 following formula: MIN (L:W) x MAX(L:W)/2 . Data are plotted as mean tumor volume +/standard error of the mean. 5 10 15 20 Treatment Tumor Volume (mm3) on Day 36 Vehicle 1,599 Gemcitabine 1,171 1200 400 200 0 3 Tumor Volume (mm 3 600 ) 1400 1200 ) 1400 800 1000 800 600 400 200 10 15 20 Days after Tum or Inoculation 25 40 45 T/C Value (%) on Day 36 P value 0.019 1000 800 600 400 200 0 0 5 35 Subcutaneous SKOV-3 Human Ovarian Cancer Xenograft Model 1200 1000 30 73 1400 0 25 Days after Tum or Inoculation Subcutaneous A549 Human Lung Cancer Xenograft Model Tumor Volume (mm Tumor Volume (mm 3 ) Subcutaneous HCT-116 Human Colon Cancer Xenograft Model 0 0 10 20 30 Days after Tum or Inoculation 40 0 10 20 30 40 50 Days after Tumor Inoculation Find out more: www.noblelifesci.com [email protected] 301.861.0009 800.602.9950 60