Our Services

Laboratory Animal Services

Time Course Assessment of Tumor Response to Therapeutics

  • Provides tumor monitoring by longitudinal imaging (MRI or ultrasound).
  • Includes biomarker evaluation, cryopreserved tissues and plasma.
  • Available in Kras/p53 pancreatic ductal adenocarcinoma or Kras/p53 non-small cell lung cancer mice.
  • Includes sufficient basic consultation with a subject matter expert.

Process

Kras/p53 pancreatic ductal adenocarcinoma mice

  • Breed 25 KPC animals with the intent of generating a cohort of 20 animals with confirmed tumor-load matching the following enrollment criteria: 
    • Female mice are considered eligible for enrollment when ultrasound examination within 24 hours reveals 1 or 2 tumors, with the largest size being 6–11 mm and a combined tumor volume of 100–350 mm3.
    • Animals with three or more tumors per organ; cystic tumors; signs of intestinal, pancreatic, or gall bladder duct occlusions; or otherwise moribund/showing signs of dilapidation will not be included in the study.
  • Collect one set of five animals for each of the four treatment arms at four weeks after treatment onset.
  • Perform necropsies to collect blood and tissues of interest, (pancreas with tumor[s] and attached portion of gastrointestinal tract, liver, lungs, skeletal muscle, and brain).
  • Perform pathology evaluation and prepare slides for histochemical evaluation of up to five biomarkers selected from the following set:
    • proliferation markers (Ki67/ClC3, pERK, pAKT, and pMEK)
    • stromal component/desmoplasia (Mason’s trichrome and collagen)
    • immune infiltrates (CD3, CD4/CD8, B220, F4/80, and FoxP3)
    • oxidative stress markers (Cox2, CA9. HIF1a, and ROS)
    • epithelial-to-mesenchimal markers (vimentin and E-cadherin)

Note: The exact set of biomarkers will be determined prior to the initiation of this study.

  • Assess disease outcomes for all collection groups and prepare a summary report.
    • Alternatively, provide samples to the requestor.
    • Plasma and tissues will be provided for further endpoint evaluation.
  • Takes about five months to complete.
Group Treatment Dose/Schedule Collection at n
1 Vehicle TBD* IP, q4d x 8 4 weeks, X* hrs post-treatment 5
2 SoC(gemcitabine) 100mg/kg IP; q3d 4 weeks, X* hrs post-treatment 5
3 AS1 TBD* IP, q4d x 8 4 weeks, X* hrs post-treatment 5
4 AS2 TBD* IP, q4d x 8 4 weeks, X* hrs post-treatment 5

TBD* - Dosing concentrations will be provided by the requestor prior to the study beginning.

Kras/p53 non-small cell lung cancer mice

  • Induce a cohort of 30 KrasG12D;p53fl/fl mice by intratracheal instillation of AdenoCre recombinase to generate 20 KrasG12D;p53-/- mice for a short-term response to treatment study.
  • Post-induction (after eight to nine weeks), pre-screen all mice by MRI for the presence of tumors and to randomize mice into treatment groups by tumor size.
  • Treat 20 mice (five per group) with vehicle, chemotherapy, and two dose levels of the requestor’s compound (AE1) daily and necropsied after one week of treatment for blood and tissue collection.
    • All mice will receive a post-treatment MRI scan prior to necropsy.
    • Based on the requestor’s guidance, mice will be necropsied at a specified number of hours post-last treatment after the final dose.
  • Conduct a full pathology evaluation and histologic analysis for four biomarkers.
  • Estimated time to dosing is 12 months.
Group Treatment Dose/Schedule Collection at n
1 Vehicle TBD PO, 3 wks on, 1 wk off 1 week, X hrs post-treatment 5
2 (Carboplatin) 25mg/kg IP; qd x 5 1 week, X hrs post-treatment 5
3 AE1 (Dose A) TBD PO, 3 wks on, 1 wk off 1 week, X hrs post-treatment 5
4 AE1 (Dose B) TBD PO, 3 wks on, 1 wk off 1 week, X hrs post-treatment 5

TBD* - Dosing concentrations will be provided prior to initiation of study by the requestor. Dose schedule: PO, QD, 1 week.

Let's Talk

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Serguei Kozlov, Ph.D. Service Contact