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What are some the known carcinogenic compounds? What types of cancer do they produce?
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benzene, tar, mineral oil, mustard gas, soot, vinyl chloride; many induce skin cancer on contact or lung cancer if inhaled
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What is anaplasia? What causes it?
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anaplasis is the loss of structural differentiation; it is caused by accelerated cell growth and mitotic rate
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What do anaplastic cells look like? What ability do they lose?
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transformed cells lose their adult morphology; they lose any ability to divide into adult cells and more closely resemble undifferentiated embryonic cells
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Describe the protein synthesis changes induced by oncogenes:
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proteins are synthesized in greater quantity than normal during tumor cell transformation; these proteins include growth factors, growth factor receptors, cytoplasmic signal transducers (i.e. ras gene), transcription factors; tumors are autocrine cells
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What is the cancer theory we are studying?
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initiation - promotion - progression theory
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What is initiation?
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Phase 1 of the Initiation-Promotion-Progression Theory; a single exposure to factors causing irreversible DNA damage (mutation) of one cell -> transformation to a cancer cell
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What is the function of proto-oncogenes?
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proto-oncogenes normally direct controlled mitosis and cell differentiation
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What is the significance of morphology in tumor cells?
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tumor cells are variable in size/shape, contain large abnormal nuclei, bear little resemblance to normal adult cells (undifferentiated); these changes are due to increased mitotic rate, abnormal chromosome structure, & loss of normal cellular arrangement
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What are tumor cell markers in tumors?
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tumor cells secrete tumor cell markers, which are chemical substances, and include hormones, enzymes/isoenzymes, antigens, and antibodies
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What is the significance of the increase in transcription factors produced by the tumor cell?
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enable genes to produce more mRNA for increased protein synthesis
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What is plasminogen activator?
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a protease secreted by tumor cells that converts plasminogen to plasmin; this protease degrades the extracellular matrix leading to loss of adhesion
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What is the significance of the increase in growth factors and cytoplasmic signal transducers produced by the tumor cell?
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growth factors: trigger cell growth by binding to an increasing # of growth factor receptors; cytoplasmic signal transducers: amplify the signals sent from the growth factors binding to the receptors
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What is the significance of adhesiveness in tumor cells?
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tumor cells are not connected to each other and have a greater chance of metastasis
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What is the function of the Rb and P53 genes? What happens when these genes become defective?
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the normal functiono of Rb and P53 genes is to trigger apoptosis - pre-programmed cell death in damaged cells; defective genes fail to trigger apoptosis of damaged cells, allowing them to lose senescence and become immortal
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What are telomeres? What is their significance?
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telomeres are segments at the ends of DNA which are terminators (terminal sequence); the telomeres shorten after each cell division; after a set number of mitotic divisions (perhaps 50-60), the cells have lost all their telomeres
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What are mutations?
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spontaneous and/or induced genetic changes
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How do damaged tumor suppressor gene cells become autonomous?
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by losing dependence from normal cellular controls
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What are the descendants of a single transformed cell called?
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they are said to be of monoclonal origin
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Describe the carcinogenic effect of microorganisms:
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some microorganisms carry their own oncogenes similar to cellular proto-oncogenes
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What is the function of the bcl gene?
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it blocks growth; damage to this gene eliminates normal growth inhibition
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What is senescence?
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aging
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What is the function of the tumor suppressor gene? What happens as a result of the initiation phase?
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it normally regulates controlled cellular growth; the initation phase causes the tumor suppressor gene to become defective, allowing them to become autonomous, lose senescence and become immortal
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What is a cancerous tumor?
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an abnormal, undifferentiated mass of cells which ultimately exhibits malignant behavior
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Describe the carcinogenic effect of radiation:
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UV light and X-rays cause skin cancer
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What are 2 types of mutations that enable the transformation to a cancer cell?
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mutations of proto-oncogenes to oncogenes (tumor promoters) and mutation of tumor suppressor genes
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What is the significance of fibronectins membrane glycoprotein?
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because tumor cells lose their normal adult shape and adhesion to neighboring cells leading to metastasis; fibronectins function as adhesive ligand-like molecules and therefore their number is reduced in tumors
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How prevalent are inherited cancers?
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inherited cancers are rare as it would indicate DNA damge to germ cells; DNA damage is more common to somatic cells than to germ cells
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What are RNA type viruses? What is an example and what type of cancer does it cause?
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RNA type viruses are retroviruses; an example is the human T-cell leukemia/lymphoma virus (HTLV) which causes T-cell lymphoma
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What is an autocrine cell?
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autocrine cells produce substances needed for their own growth
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What is PSA and alpha-fetoprotein?
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PSA is prostate specific antigen, a tumor marker, which is screted by prostate cancer cells; alpha-fetoprotein is a tumor marker secreted by liver, ovarian, and testicular cancer cells
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What type of cancer is heliobacter pylori responsible for?
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heliobacter pylori causes ulcers and possiblly leads to stomach cancer
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How do transformed cells avoid apoptosis? What is the significance of this?
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cells initiated to transform make a telomerase enzyme which repairs the telomeres after each cell division; since the telomeres never shorten, the cells are immortal
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What are some known carcinogens?
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radiation, chemicals, certain compounds, microorganisms, DNA & RNA type viruses, heliobacter pylori
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What is progression?
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the 3rd stage of carcinogenesis
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What is the significance of a proliferative life span of cancer tumor cells?
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tumor cells display accelerated mitotic rate, increase in chromosomal abnormalities, and incress in cell numbers; tumor cells become immortal
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What is neurofibromatosis?
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aka elephant man; this is an inherited cancer
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What triggers apoptosis?
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the loss of telomeres signal Rb or P53 genes to trigger apoptosis
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Are tumor markers chemicals that are only secreted by cancer cells?
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sometimes tumor markers are substances secreted only by cancer cells (ex: PSA, alpha-fetoprotein); in other cases, tumor markers are elevated levels of normally secreted substance (ex: estrogen in reproductive cancers)
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What is promotion?
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the 2nd phase of carcinogenesis; it is characterized by multiple exposures to factor(s) causing irreversible proliferation of many cancer cells from one transformed cell
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What is the significance of actin filaments in tumor cells?
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tumor cells display degeneration of actin filaments which reduces adhesion to neighboring cells and ultimately loss of density-depending inhibition of growth
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What are some carcinogenic chemicals?
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nickel, chromium, and cadmium metals; also, asbestos and arsenic
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What is the genetic component of promotion?
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oncogenes are turned on while tumor suppressor genes are turned off
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What are 3 genes involved in normal cellular control? What types of genes are these?
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the bcl gene and the Rb and P53 genes; these genes are tumor suppressor genes
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What is carcinogenesis?
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abnormal cell growth & development caused by DNA damage leading to malfunction of 2 sets of control genes: proto-oncogenes and tumor suppressor genes
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What is the significance of the loss of morphology?
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loss of morphology is associated with loss of function
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What are some DNA type viruses and the types of cancer they initiate?
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HPV (human papilloma virus) causes genital warts and can initiate cervical cencer; Epstein-Barr virus initiates lymphoma; Hepatitis B & C can cause hepatic cancer
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What are the 4 factors that allow for promotion?
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genetic, nutrition, infection, and hormones
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What is malignancy?
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the spread (metastasis) of the tumor cells to distant sites
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How do oncogenes promote tumors?
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oncogenes induce hyperactive cell growth by stimulating protein synthesis; they initiate/promote tumor cell transformation
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What happens during mitosis of the anaplastic cell?
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more undifferentiated cells are produced from mitosis which will never develop into functional adult cells
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What are the characteristics of malignant tumors? (10)
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density, growth factor requirements, anchorage dependence, proliferative life span, adhesiveness, morphology, fibronectins membrane glycoprotein, plasminogen activator, actin filaments. tumor cell markers
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What is the role of infection on promotion?
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immunosuppression allows cancer cell proliferation to go undetected by the immune system
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What is the significance of density regarding cancerous tumors?
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tumor cells display continuous growth even when in contact with other cells (i.e. no contact inhibition) due to increased, growth factors, decreased adhesion (anchoring junctions) and cell-cell communication (gap junction)
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What stage is tumor development? What is is caused by?
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progression; increased mitotic rate of a small group of transformed cells
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What is the significance of anchorage dependence of cancer tumor cells?
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tumor cells display degeneration of cell-cell attachments (i.e. anchoring junctions for structure and gap junctions for communication) leading to metastasis
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What is the role of hormones on promotion?
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estrogen promotes female reproductive cancer proliferation; testosterone promotes male reproductive cancer (i.e. prostate) proliferation
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What is the significance of growth factor requirements regarding cancer tumor cells?
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tumor cells need little growth factor and produce their own (autocrine); tumor cells ignore growth inhibition factors (i.e. interferon, tumor necrosis factor)
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What is the role of nutrition on promotion?
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nutrition must be sufficient to support cancer cell growth
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