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In vivo experiments have become increasingly important in publication of small molecule or tumor driver studies. These experiments are technical and can be costly to initiate. At the PRR, we strive to make this barrier easier to cross. We maintain breeding colonies for several strains of mice, have the surgical expertise to transplant tumor cells or chunks, and can identify and process tissue upon necropsy.

Fees

The Preclinical Research Resource provides cost-effective access to specialized services such as: human/mouse xenografts, patient-derived xenograft (PDX) models, and non-invasive imaging.

Fees for PRR services are based on an hourly rate of $52.09.

For your reference, a chart comparing our prices to similar shared resources at other cancer centers. View the HCI Preclinical Research Resource Price Comparison.

Forms

Work Authorization Form

For internal users with chartfield numbers.

Project Request Form

This form will include the details of your experiment and specify tissue for necropsy.

Letter of Support Request

If you would like to work with our facility and need a letter of support for a grant, please email us with a short outline of your study goals

Tumor Type and Growth Site

When initiating an in vivo tumor experiment, the first important factors to consider are the tumor cells and growth location best suited for your needs.

Several models for tumor growth area available, including PDX, cell lines, and transgenic mice. Each has advantages and disadvantages.

Patient-Derived Xenografts (PDX)

Description

  • Transplanted directly from human patients into mice
  • Thought to provide the closest genetic representation to human cancer.

Advantages

  • Genetically similar to human patients
  • Growth time of 2-3 months
  • Several successful examples of preclinical experiments working in clinical trials

Disadvantages

  • Must be grown in a mouse with a compromised immune system, so immune and tumor cell interactions are lost
  • Limited material and tumor types

Cell Lines

Description

  • Derived from either human or mouse tumors
  • Grown in culture dishes
  • Versatile tool for knockdown and in vitro assays

Advantages

  • Easy to maintain and manipulate
  • Tumor growth in 1-2 months
  • Many models and tumor types available

Disadvantages

  • Altered genetic mutations after years out of the host and being grown on plastic

Genetically Engineered Models

Description

  • One or several genes are mutated in the DNA of mice, creating a new strain that develops cancer spontaneously
  • Works best for studying genes involved in cancer development and progression

Advantages

  • Known genetic alterations
  • No surgery required for tumor growth
  • Intact immune system
  • Several tumor models established

Disadvantages

  • Difficult to produce
  • Do not fully represent the genetic complexity of human tumors
  • Do not reliably predict success of treatments in human patients

If you have been working with a cell line in the lab, it may be best to transplant that cell line subcutaneously. A subcutaneous injection is done just under the skin, usually in the shoulder or hip area of the mouse. The benefits of subcutaneous injection are ease of transplant, shorter mouse recovery time, ready blood supply, and accessibility to measure tumor growth with calipers. With these benefits, a subcutaneous injection is commonly used for tumor studies.

Alternatively, you may want the tumor to grow within its normal microenvironment, within the organ of origin. This is called an orthotopic growth model. Common sites are the mammary gland, tibia, and colon. These surgeries are more complex, and usually require bioluminescent imaging to monitor the growth of the tumor. However, these models are thought to better simulate the tumor microenvironment and progression occurring in humans.

Investigational drug studies

For an investigational drug study, the proper dose and route are important considerations. Optimization must occur to find a suitable solvent, and often a maximum tolerable dose study will be performed. This study uses increasing concentrations of the compound to find a dose that is lethal to 10% of the mice. When that concentration is found, one-tenth of that concentration is used for daily dosing.

Several additional routes are available for dosing. The most common include intraperitoneal (within the organ cavity), oral gavage (via the stomach), and intravenous (into the bloodstream). Depending on the stage of molecule discovery, intraperitoneal or intravenous routes may be more preferable, as the drug does not have to cross the membrane of the gut. Pharmacokinetic studies can determine the best route and the time it takes the molecule to metabolize in the body.

Tissues Collected Upon Necropsy

Mice need to be sacrificed when the tumor size reaches two centimeters or when the mice are in pain or distress. The tissue types you need after sacrifice will depend on the study, but usually include tissue for histology, RNA/DNA, and chunks for potential re-transplant. In addition, you may want metastatic organs or blood to find circulating tumor cells or immune cells.

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