Cancer Pathogenesis and Mouse Models
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Questions and Answers

Which of the following is NOT a step in the process of tumorigenesis?

  • Metastasis
  • Regeneration (correct)
  • Promotion
  • Initiation

    • Mouse models in cancer research tend to develop a higher incidence of metastases compared to other animals.

    False

    What is the primary genetic characteristic of inbred mice used in cancer research?

    Identical genetic background

    The process involving the accumulation of multiple genetic aberrations that transforms normal cells is known as __________.

    <p>tumorigenesis</p> Signup and view all the answers

    Match the advantages of using mouse models in cancer research with their respective descriptions:

    <p>Small size = Easy handling and management Cost-effective = Cheaper than larger animal models High tumor incidence = Allows observation of rapid tumor growth Genetic characterization = Best characterized of all mammals used in research</p> Signup and view all the answers

    What is the primary origin of transplantable tumor models?

    <p>Established cancer cell lines or patient-derived xenografts</p> Signup and view all the answers

    Genetically engineered tumor models (GEMMs) arise spontaneously from established cancer cell lines.

    <p>False</p> Signup and view all the answers

    What defines humanized models?

    <p>Immunodeficient animals engrafted with human cells or tissues for cancer study.</p> Signup and view all the answers

    Transplantable tumor models can be derived from established cancer cell lines or patient-derived ______.

    <p>xenografts</p> Signup and view all the answers

    Match the following tumor models with their characteristics:

    <p>Transplantable tumor models = Tumor is transplanted into host animals Genetically engineered tumor models = Arises from engineered mutations Humanized models = Immunodeficient animals engrafted with human cells Tumors from cell lines = Derived from established cancer cell lines</p> Signup and view all the answers

    What is a significant strength of transplantable tumor models?

    <p>Rapid tumor formation</p> Signup and view all the answers

    GEMMs provide a limited modeling of tumor progression and TME.

    <p>False</p> Signup and view all the answers

    What is one limitation of humanized mice models?

    <p>Logistically difficult to obtain matched donor and tumor samples</p> Signup and view all the answers

    One direction for transgenic mouse cancer models is to replicate specific human cancer __________ in mouse models.

    <p>mutations</p> Signup and view all the answers

    Match the following models with their respective strengths:

    <p>Transplantable tumors = Simplicity and rapid formation GEMMs = Genetic lesions found in human cancers Humanized mice = Human immune populations studied directly</p> Signup and view all the answers

    What is a key limitation of GEMMs?

    <p>They incur increased cost and complexity</p> Signup and view all the answers

    Humanized mice can completely reconstitute the human immune response.

    <p>False</p> Signup and view all the answers

    Name one of the current directions for transgenic mouse cancer models.

    <p>Personalizing humanized mice</p> Signup and view all the answers

    What is one of the general limitations of GEMMs regarding tumor development?

    <p>Latent development can vary dramatically</p> Signup and view all the answers

    GEMMs allow for the invasive monitoring of tumor development.

    <p>False</p> Signup and view all the answers

    What gene construct is used as a positive selective marker in gene targeting by homologous recombination?

    <p>Neomycin resistance gene</p> Signup and view all the answers

    The _____ gene is used as a negative selective marker in gene targeting.

    <p>TK</p> Signup and view all the answers

    Match the following steps in the process of targeted manipulation of mouse embryonic stem cells with the corresponding actions:

    <p>1 = Selection of transgenic cell line (neor &amp; TK gene) 2 = Injection into blastocysts 3 = Obtain chimeric mouse 4 = Crossing to obtain homozygous genetically engineered mouse</p> Signup and view all the answers

    Which technology is used for conditional gene modification?

    <p>Cre-Lox technology</p> Signup and view all the answers

    The process of Cre-Lox Technology involves the use of a promoter that can be tissue-specific.

    <p>True</p> Signup and view all the answers

    What is the primary purpose of the TK gene in gene targeting?

    <p>To initiate cell death in randomly integrated gene constructs</p> Signup and view all the answers

    What type of cells are used in an allograft model?

    <p>Mouse cancer cell lines or tissues</p> Signup and view all the answers

    The xenograft model can use human tumor cells derived from a patient.

    <p>True</p> Signup and view all the answers

    What is a primary advantage of the allograft model?

    <p>Results can be analyzed in an environment that closely recapitulates real scenarios.</p> Signup and view all the answers

    The xenograft model is typically conducted in _____ mice.

    <p>immunocompromised</p> Signup and view all the answers

    What is one limitation of the xenograft model?

    <p>It requires immunocompromised hosts.</p> Signup and view all the answers

    Match the following models with their primary application:

    <p>Allograft Model = Preclinical development of anti-cancer therapeutics Xenograft Model = Toxicity studies from targeted therapies</p> Signup and view all the answers

    Both allograft and xenograft models allow for the study of immune responses in tumors.

    <p>False</p> Signup and view all the answers

    What is a key characteristic of the host species in an allograft model?

    <p>Immunocompetent mice</p> Signup and view all the answers

    What is the purpose of immersing tumor pieces in media such as glycerol-glucose?

    <p>To maintain them in a viable state for storage</p> Signup and view all the answers

    Retrovirus-mediated techniques lead to precise gene integration in genetically engineered mouse models.

    <p>False</p> Signup and view all the answers

    What should be done immediately after thawing tumors?

    <p>They should be inoculated in mice.</p> Signup and view all the answers

    The microinjection method involves the direct injection of foreign DNA material into a __________ mouse zygote.

    <p>fertilized</p> Signup and view all the answers

    Match the following genetically engineered mouse model techniques with their characteristics:

    <p>Retrovirus-Mediated = Random integration of genetic material Microinjection = Direct injection into fertilized zygote Targeted manipulation of mouse embryonic stem cells = Precise integration at specific loci</p> Signup and view all the answers

    What is a limitation of using retrovirus-mediated techniques?

    <p>Random integration can disrupt essential genes</p> Signup and view all the answers

    Targeted manipulation of embryonic stem cells is a time-consuming and technically challenging process.

    <p>True</p> Signup and view all the answers

    What can be created using targeted manipulation of ES cells?

    <p>Loss-of-function and conditional models.</p> Signup and view all the answers

    Once the tumor develops to an appropriate size, the response to __________ can be studied in vivo.

    <p>therapeutic regimes</p> Signup and view all the answers

    Which of the following advantages is associated with microinjection techniques?

    <p>High versatility for expressing transgenes</p> Signup and view all the answers

    Study Notes

    Cancer Pathogenesis and Process

    • Tumorigenesis is a complex process involving multiple genetic alterations that transform normal cells, enabling abnormal growth, proliferation, and metastasis.
    • Initiation, Promotion, Progression, and Metastasis are the four stages.

    Mouse Models in Cancer Research

    • Advantages:
      • Small size, easy to handle.
      • Cheaper than other animal models.
      • High incidence and rapid growth of tumors.
      • Multiple mice can be treated simultaneously for dose-response studies.
      • Well-characterized genetically compared to other mammals used in research.
    • Limitations:
      • Differences in size, lifespan, organ morphology, and physiology compared to humans.
      • Differences in pharmacokinetics and pharmacodynamics (PK/PD).
      • Differences in telomerase activity (largely inactive in adult humans).
      • Tend to develop fewer metastases than humans.
      • Differences in metabolic rate and pathways lead to different drug responses.
      • Limited number of initiating genetic alterations in tumors compared to humans; mouse tumors are often more homogeneous.

    Different Types of Experimental Tumor Mouse Models for Cancer Immunology Research

    • Transplantable tumor models:

      • Tumors are transplanted from established cancer cell lines or patient tissues into host animals.

    • Genetically engineered tumor models (GEMMs):

      • Tumors arise endogenously due to engineered mutations in specific genes.

    • Humanized Models:

      • Immunodeficient animals are engrafted with human cells/tissues to study human cancer.
      • Derived from human cancer cells or tissues transplanted into humanized mice.

    Different Types of Transplantable Tumor Models

    • Allograft (Syngenic) Model:
      • Tumors or cancerous cells are of mouse origin transplanted into a host mouse with a specific genetic trait.
      • Mouse cancer cell lines or tissues are used.
      • Immunocompetent mice are used; results closely recapitulate the real scenario.
    • Xenograft (PDX) Model:
      • Human tumor cells are transplanted into a host.
      • The transplantation can be subcutaneous or orthotopic.
      • Human cancer cell lines or patient-derived xenografts (PDXs) are used.
      • Severely compromised/immunodeficient mice are used to mimic human tumor genetics and biology.

    Steps in Preparing Transplantable Tumor Models

    • Obtain tumors and store them frozen in media such as glycerol-glucose.
    • Incubate small tumor pieces in media and place them in sterile ampoules.
    • Slowly cool ampoules to storage temperature, then quickly thaw to inoculate into mice.
    • Depending on tumor size, observe the response to therapeutic regimes.

    Different Types of Genetically Engineered Mouse Models

    • Retrovirus-Mediated:
      • Retroviruses introduce genetic material into host cells; integration is random.
      • Simple and quick.
    • Microinjection:
      • Foreign DNA is directly injected into a fertilized mouse zygote.
      • Allows target gene expression; integration is random.
    • Targeted manipulation of mouse embryonic stem (ES) cells:
      • Modifies specific cells in mouse ES cells, inducing into the developing embryo.
      • Precise; targeted integration.
      • High precision.

    Gene Targeting using Homologous Recombination

    • Targeting vector: includes a selectable marker (neomycin resistance gene) and a negative selectable marker (HSV-tk gene).
    • Neo gene: positive selectable marker.
    • TK gene: negative selectable marker; triggers cell death.
    • Embryogenic stem cells are targeted using electroporation and homologous recombination.
    • The process results in the generation of genetically modified mice.

    Conditional Gene Modification Using Cre-Lox Technology

    • Cre-line & Floxed line: Two different mouse lines are used.
    • Floxed gene: The gene to be targeted is flanked by two LoxP sites.
    • Crossing: Crossing the Floxed line with the Cre-line results in the progeny the gene between the LoxP sites being removed, generating a knockout allele.

    Humanized Murine Models

    • Hematopoietic stem cells (CD34+) from patients are injected in NSG mice.
    • The immune system and host cells are reconstructed to make the mouse more human-like.

    Humanized Tumor Models

    • Advantages: Can model tumor development complexities, genomic heterogeneity, and tumor microenvironment.
    • Limitations: Requires high tumor take rates across multiple mice in a reasonable time frame. Repeated invasive sampling for hematopoietic cells might be necessary.

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    Description

    Explore the intricate process of tumorigenesis and the role of mouse models in cancer research. Understand the stages of cancer development and the advantages and limitations of using mice for experimental studies. This quiz will test your knowledge on both the biological processes and the methodologies in cancer research.

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