Lecture 21
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Questions and Answers

What is the result of a balanced translocation in tumor cells?

  • Loss of a whole chromosome
  • Amplification of a particular gene
  • Exchange of segments between two chromosomes (correct)
  • Deletion of a segment of a chromosome
  • What type of chromosomal abnormality is commonly seen in solid tumors?

  • Gene amplification
  • Deletion of a segment of a chromosome (correct)
  • Aneuploidy
  • Balanced translocation
  • Which of the following genes is amplified in neuroblastoma?

  • HER-2
  • BCR-ABL
  • RET
  • N-MYC (correct)
  • What is the term for a chromosome number that is not a multiple of 23 in humans?

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

    What is the function of BCL-2 in apoptosis?

    <p>To maintain the balance between pro-apoptotic and anti-apoptotic molecules</p> Signup and view all the answers

    What is the result of gene amplification in tumor cells?

    <p>Increased production of a particular gene</p> Signup and view all the answers

    What is required for the development of cancer?

    <p>The accumulation of multiple mutations</p> Signup and view all the answers

    Which gene is responsible for protecting tumor cells from apoptosis in follicular lymphoma?

    <p>BCL-2</p> Signup and view all the answers

    What is the role of TP53 in apoptosis?

    <p>It induces apoptosis in cells with irreparable DNA damage</p> Signup and view all the answers

    What is the first step in the process of invasion and metastasis?

    <p>Detachment of tumor cells from each other</p> Signup and view all the answers

    What is the function of proteolytic enzymes in invasion and metastasis?

    <p>They degrade the extracellular matrix</p> Signup and view all the answers

    What determines the metastatic site of a tumor?

    <p>The location of the primary tumor and its vascular and lymphatic drainage</p> Signup and view all the answers

    What is the role of vascularization in tumor growth and metastasis?

    <p>It is essential for tumor growth and metastasis</p> Signup and view all the answers

    What is organ tropism in the context of metastasis?

    <p>The ability of tumor cells to migrate to specific organs</p> Signup and view all the answers

    What is the primary reason individuals with inherited defects in DNA repair genes are at greater risk for cancer development?

    <p>Because of their inability to repair DNA damage</p> Signup and view all the answers

    What is the outcome of environmental hazards causing DNA damage in normal cells?

    <p>Repair of DNA damage</p> Signup and view all the answers

    What is the result of the failure to repair DNA damage in cells?

    <p>Genomic instability</p> Signup and view all the answers

    What is the characteristic of tumor cells that are more adept at evading host defenses?

    <p>Increased aggression</p> Signup and view all the answers

    What is the role of BRCA1 and BRCA2 in familial breast cancers?

    <p>Involvement in DNA repair</p> Signup and view all the answers

    What is the result of clonal expansion of tumor cells?

    <p>Progression to malignancy</p> Signup and view all the answers

    What is the characteristic of hereditary nonpolyposis colon cancer syndrome (HNPCC)?

    <p>Defective DNA repair</p> Signup and view all the answers

    What is the outcome of genetic damage during carcinogenesis?

    <p>Small genetic damage</p> Signup and view all the answers

    What is the role of VEGF in tumor cells?

    <p>Promoting angiogenesis</p> Signup and view all the answers

    What is the function of HIF in response to hypoxia?

    <p>Activating VEGF transcription</p> Signup and view all the answers

    What is the role of the VHL gene in tumor suppression?

    <p>Inhibiting HIF</p> Signup and view all the answers

    What is the reason for cellular senescence after 60-70 cell doublings?

    <p>Progressive shortening of telomeres</p> Signup and view all the answers

    What is the effect of P53 and RB mutations on cellular senescence?

    <p>Cells cannot recognize DNA damage and keep dividing</p> Signup and view all the answers

    What is the role of telomerase in cancer cells?

    <p>Reacting telomere segments in chromosomes</p> Signup and view all the answers

    What is the result of multiple mutations in different cells during tumor progression?

    <p>Generation of heterogenous cells with different characteristics</p> Signup and view all the answers

    What is the significance of VEGF antibody in cancer treatment?

    <p>It is now approved for treatment of some cancer</p> Signup and view all the answers

    Study Notes

    Resisting Cell Death (Apoptosis)

    • BCL-2 controls apoptosis by balancing pro-apoptotic (BAX, BAK) and anti-apoptotic molecules
    • Apoptosis can be activated by intrinsic (mitochondrial) and extrinsic pathways, leading to caspase activation
    • Mitochondrial membrane permeability is regulated by BCL2
    • In 85% of follicular lymphoma cases, the anti-apoptotic BCL2 gene protects tumor cells from apoptosis
    • TP53 is a pro-apoptotic gene that induces apoptosis in cells with irreparable DNA damage

    Activating Invasion and Metastasis

    • Divided into three steps: invasion of extracellular matrix, vascular dissemination, and homing of tumor cells
    • Invasion involves detachment of tumor cells from each other, degradation of basement membrane and interstitial matrix, and attachment to new binding sites
    • Vascular dissemination and homing of tumor cells involve adhesion to vascular endothelium and entrance into other organ parenchyma
    • Metastatic site prediction is influenced by primary tumor location and vascular and lymphatic drainage
    • Organ tropism is exhibited by some tumors, possibly due to activation of adhesion or chemokine receptors

    Inducing Angiogenesis

    • Vascularization of tumor cells is essential for growth and metastasis
    • Hypoxia activates HIF1α, leading to transcription of VEGF genes and subsequent angiogenesis
    • VEGF secreted by tumor cells leads to new vessel formation
    • HIF1α is inactivated by VHL gene (tumor suppressor gene)
    • VEGF antibody is approved for treatment of some cancers

    Enabling Replicative Immortality

    • Cells lose capacity to divide and enter senescence after 60-70 cell doublings due to telomere shortening
    • Short telomeres are recognized as DNA damage, leading to cell cycle arrest mediated by P53 and RB
    • Cancer cells can reactivate telomerase, achieving immortality
    • Cells with mutation in P53 and RB genes cannot recognize DNA damage and continue to divide

    The Molecular Basis of Cancer

    • Carcinogenesis is a multistep process resulting from multiple genetic alterations
    • Tumor progression and heterogeneity result from multiple mutations accumulating independently in different cells
    • New subclones arise from the descendants of the original transformed cell by multiple mutations
    • Environmental hazards, inherited mutations, and DNA damage contribute to carcinogenesis

    Genomic Instability

    • Normal cells are able to repair DNA damage
    • Individuals with inherited defects in DNA repair genes are at greater risk for cancer development
    • Examples include Hereditary non-polyposis colon cancer syndrome, Xeroderma pigmentosum, and BRCA1 and BRCA2 in familial breast cancers

    Karyotopic Changes in Tumors

    • Genetic damage during carcinogenesis can result in small (point mutations) or large chromosomal changes
    • Common types of structural abnormalities in tumor cells include balanced translocations, deletions, gene amplification, and aneuploidy
    • Examples of balanced translocations include the Philadelphia (Ph) chromosome in chronic myelogenous leukemia and t(8;14) in Burkitt’s leukemia/lymphoma

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    Description

    This quiz covers the hallmarks of cancer, specifically resisting cell death through apoptosis. Learn about the roles of BCL-2, BAX, and BAK in regulating apoptosis and mitochondrial membrane permeability.

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