Cancer Biology and Epigenetics
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Questions and Answers

What factors regulate angiogenesis?

p53, RAS, MYC, MAPK signaling

Which enzymes mediate basement membrane and interstitial matrix degradation in invasion and metastasis?

  • CD8+ CTLs
  • BRCA1 and BRCA2
  • MMPs and cathepsins (correct)
  • E-cadherin
  • Tumor antigens are presented on the cell surface by MHC class II molecules.

    False

    Defects in the homologous recombination DNA repair system lead to syndromes such as Bloom syndrome, ataxia-telangiectasia, and Fanconi __________.

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

    Match the microbial agent with the associated cancer type:

    <p>HTLV-1 = Adult T-cell leukemia/lymphoma HPV = Cervical cancer EBV = Burkitt lymphoma H.pylori = Gastric adenocarcinoma</p> Signup and view all the answers

    What is neoplasia?

    <p>Neoplasia refers to 'new growth' of a collection of cells and stroma composing new growths, referred to as neoplasm or tumor.</p> Signup and view all the answers

    How are benign tumors typically named?

    <p>-oma</p> Signup and view all the answers

    Benign tumors are generally well-differentiated and composed of cells resembling mature normal cells.

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

    __________ is the spread of a tumor to sites that are physically discontinuous with the primary tumor.

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

    Match the following tumor nomenclature with their meanings:

    <p>Adenoma = Benign epithelial neoplasm with glandular pattern Papillomas = Epithelial neoplasms producing visible projections from surfaces Sarcomas = Malignant tumors arising in mesenchymal tissue Carcinomas = Malignant neoplasms of epithelial origin</p> Signup and view all the answers

    What is the basis for the grading of cancer?

    <p>degree of differentiation of the tumor cells and number of mitoses</p> Signup and view all the answers

    How are cancers classified based on grading?

    <p>Grades I to IV</p> Signup and view all the answers

    What is the basis for the staging of cancers?

    <p>size of primary lesion, extent of spread to regional lymph nodes, presence of blood-borne metastases</p> Signup and view all the answers

    What does the 'T' stand for in the TNM system for cancer staging?

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

    Immunohistochemistry can help categorize undifferentiated malignant tumors.

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

    Flow cytometry can rapidly measure several individual cell characteristics, such as membrane antigens and DNA content of tumor cells.

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

    Match the tumor marker with the associated cancer:

    <p>CA-125 = Ovarian cancer Prostate-specific antigen = Prostate cancer Alpha-fetoprotein (AFP) = Liver cell cancer and non-seminomatous germ cell tumors of the testis</p> Signup and view all the answers

    What determines which genes are silenced and which are expressed in tumourigenesis?

    <p>Epigenetic changes</p> Signup and view all the answers

    What is the effect of epigenetically silencing a tumour suppressor gene?

    <p>Loss of tumor suppression</p> Signup and view all the answers

    Which genes cause excessive cell growth and proliferation even without external growth factors in tumour cells?

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

    Match the following tumor components with their characteristics:

    <p>Cyclins and Cyclin-Dependent Kinases = Unregulated G1/S progression Tumor Suppressor Genes = Brakes to cell proliferation Autocrine loop = Self stimulation by overexpressed growth factors</p> Signup and view all the answers

    Imatinib is a drug used to treat cancer by targeting nonreceptor tyrosine kinases.

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

    What is the role of the TP53 gene in cancer?

    <p>Regulates cell cycle, DNA repair, apoptosis</p> Signup and view all the answers

    Study Notes

    Neoplasia

    • Neoplasia refers to "new growth" or a collection of cells and stroma composing new growths, also referred to as neoplasm or tumor.
    • This is different from the tumor described in cardinal signs of inflammation as swelling.
    • Cancer is the common term for all malignant tumors.

    Neoplasia: Definition

    • A neoplasm or tumor is defined as a genetic disorder of cell growth, triggered by acquired or less commonly inherited mutations affecting a single cell and its colony progeny.

    Neoplasia: Nomenclature

    • All tumors, benign and malignant, are composed of two components:
      • Neoplastic cells that constitute the tumor parenchyma.
      • Reactive stroma made up of connective tissue, blood vessels, and the cells of the adaptive and innate immune system.
    • The parenchyma of the tumor determines its biologic behavior and is the component from which the neoplasm derives its name.
    • Benign tumors bear the suffix "-oma" to the cell of origin, e.g. fibroma, lipoma, and meningioma.

    Characteristics of Benign and Malignant Tumors

    • Differences between benign and malignant tumors can be discussed under the headings:
      • Differentiation and anaplasia
      • Rate of growth
      • Local invasion
      • Metastasis

    Differentiation and Anaplasia

    • Differentiation refers to the extent to which parenchymal cells resemble comparable normal cells, both morphologically and functionally.
    • Well-differentiated tumors are composed of cells resembling the mature normal cells of the tissue of origin.
    • Poorly or undifferentiated tumors have primitive-appearing, unspecialized cells.
    • Benign tumors are generally well-differentiated, while malignant tumors range from well-differentiated to undifferentiated.
    • Anaplasia, or lack of differentiation, is a hallmark of malignant transformation.

    Rate of Growth

    • Generally, most benign tumors grow slowly over a period of years, while most cancers grow rapidly, sometimes at an erratic pace.

    Local Invasion

    • Nearly all benign tumors grow as cohesive expansile masses that remain localized, with a rim of compressed connective tissue.
    • Malignant tumors, on the other hand, grow with progressive infiltration, invasion, and destruction of surrounding tissue.

    Metastasis

    • Metastasis is the spread of a tumor to sites that are physically discontinuous with the primary tumor.
    • Metastasis unequivocally marks a tumor as malignant, as benign neoplasms do not metastasize.
    • With few exceptions, all cancers can metastasize.
    • The more aggressive, rapidly growing, and larger the primary neoplasm, the greater the likelihood it has or will metastasize.

    Epidemiology

    • The worldwide cancer rate is increasing, with incidence rates stabilized in men but increasing in women.
    • The incidence rate is low in developing countries due to poor access to health facilities and poor record keeping.
    • The actual incidence rate of cancer is increasing in developing countries compared to advanced countries.
    • Common cancers in females include breast, lung, and colon/rectum cancer.
    • Common cancers in males include prostate, lung, and colon/rectum cancer.

    Environmental Factors

    • Environmental influences are the dominant risk factors for most cancers, including:
      • Obesity
      • Alcohol abuse
      • Diet
      • Smoking
      • Promiscuity
    • Cancer occurs in certain age groups, with death rates highest in women between 40-79 years and in men between 60-79 years.

    Molecular Basis of Cancer

    • Nonlethal genetic damage, clonal expansion of a single precursor cell with genetic damage, and four classes of genes that mutate contribute to the development of cancer.
    • The four classes of genes that mutate are:
      • Proto-oncogenes
      • Tumor suppressor genes
      • Programmed cell death genes
      • DNA repair genes
    • Mutations that contribute to the acquisition of cancer hallmarks are referred to as driver mutations.
    • The first mutation that starts the process is the initiating mutation, which is maintained in all daughter cells.

    Oncogenes

    • Oncogenes are mutated genes that cause excessive cell growth, even in the absence of growth factors and other growth-promoting external cues.
    • They are mutated or overexpressed proto-oncogenes that produce oncoproteins which are constitutively active and resistant to external control, leading to cell proliferation.

    Cell Cycle and Growth Control

    • Self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, and altered cellular metabolism are hallmarks of cancer.
    • Growth factors, growth factor receptors, downstream components of the receptor tyrosine kinase signaling pathway, and transcription factors all contribute to the development of cancer.
    • Examples of oncogenes include:
      • RAS
      • BRAF
      • PI3K
      • JAK/STAT
      • MYC

    Insensitivity to Growth Inhibition

    • Tumor suppressor genes, such as TP53, apply brakes to cell proliferation and are often inactivated in cancer.
    • The "two-hit" hypothesis of oncogenesis in RB explains how loss of function in both alleles of the RB gene leads to retinoblastoma.
    • TP53 is the most frequently mutated gene in human cancers, and its inactivation can lead to uncontrolled cell growth and cancer.Here are the study notes for the text:

    Cancer Biology

    • Loss of p53 function: leads to unrepaired DNA damage, driver mutations in oncogenes and cancer genes, and malignant transformation
    • TP53 mutations: lead to a mutator phenotype, where cells accumulate mutations and become cancerous
    • Tumor suppressor genes: APC, E-Cadherin, CDKN2A, PTEN, VHL, and others, which normally prevent cancer by regulating cell growth and division

    Cellular Metabolism

    • Warburg metabolism: a form of growth-promoting metabolism that favors glycolysis over oxidative phosphorylation, resulting in the production of macromolecules
    • Macromolecules produced: nucleotides, amino acids, and lipids

    Evasion of Cell Death

    • Apoptosis: programmed cell death that can be initiated through intrinsic or extrinsic pathways, leading to cell destruction
    • Anti-apoptotic mechanisms: cancer cells may overexpress BCL2 or inactivate p53 to evade apoptosis

    Limitless Replicative Potential

    • Cancer stem cells: cells that may arise from normal stem cells or mature cells that acquire stem-like properties, allowing them to proliferate indefinitely
    • Telomerase reactivation: allows cancer cells to maintain their telomeres and divide indefinitely

    Angiogenesis

    • Vascularization of tumors: essential for tumor growth, regulated by the balance between angiogenic and anti-angiogenic factors
    • VEGF: a pro-angiogenic factor produced by tumor cells, which can be inhibited by anti-angiogenic therapy

    Invasion and Metastasis

    • Steps of invasion: loosening of cell-cell contacts, degradation of ECM, attachment to novel ECM components, and migration of tumor cells
    • Loss of E-cadherin: leads to loss of cell-cell contacts and invasion

    Evasion of Immune Surveillance

    • Immune evasion mechanisms: include selective outgrowth of antigen-negative variants, loss of histocompatibility antigens, and immunosuppression
    • Cancer antigens: include products of mutated proto-oncogenes, tumor suppressor genes, and viral antigens

    Genomic Instability and Malignancy

    • Inherited mutations: in genes involved in DNA repair systems increase the risk of cancer
    • Microsatellite instability: a hallmark of some cancers, including colorectal cancer

    Carcinogenesis

    • Chemical carcinogens: directly damage DNA, leading to mutations and cancer
    • Radiation carcinogenesis: ionizing radiation causes chromosome breakage, translocations, and point mutations
    • Viruses: some viruses, such as HTLV-1, HPV, and HBV, can cause cancer through various mechanisms

    Clinical Aspects of Neoplasia

    • Local and hormonal effects: cancers can produce hormones, leading to manifestations such as Cushing's syndrome
    • Cachexia: a wasting syndrome common in cancer patients, caused by soluble factors such as inflammatory cytokines
    • Paraneoplastic syndromes: rare syndromes caused by cancer, which can mimic metastatic disease

    Grading and Staging of Tumors

    • Grading: based on the degree of differentiation and number of mitoses
    • Staging: based on the size of the primary lesion, regional lymph node involvement, and presence of metastases
    • TNM system: a widely used system for staging cancer

    Laboratory Diagnosis of Cancer

    • Immunohistochemistry: uses specific antibodies to identify cell products or surface markers
    • Flow cytometry: measures cell characteristics such as membrane antigens and DNA content
    • Molecular diagnostics: uses DNA sequencing, PCR, and other techniques to diagnose cancer and detect minimal residual disease.### Tumor Markers (Hormones)
    • Human chorionic gonadotropin is associated with trophoblastic tumors and non-seminomatous testicular tumors
    • Calcitonin is associated with medullary carcinoma of the thyroid
    • Catecholamine and metabolites are associated with pheochromocytoma and related tumors
    • Ectopic hormones are associated with tumors of the paraneoplastic syndrome group

    Tumor Markers (Isoenzymes)

    • Prostatic acid phosphatase is associated with prostate cancer
    • Neuron-specific antigen is associated with small cell cancer of the lung and neuroblastoma

    Tumor Markers (Specific Proteins)

    • Immunoglobulins are associated with multiple myeloma and other gammopathies
    • Prostate-specific antigen is associated with prostate cancer

    Tumor Markers (Mucins & Other Glycoproteins)

    • CA-125 is associated with ovarian cancer
    • CA-19-9 is associated with colon and pancreatic cancer
    • CA-15-3 is associated with breast cancer

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    This quiz covers the evolution of tumors, mutations, and epigenetic changes that influence cancer therapy and tumorigenesis.

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