Neoplasia Flashcards
What are the reversible disorders of cellular growth and differentiation in neoplasia?
Metaplasia occurs when normal cells of one type are replaced by normal cells of another type that are better able to withstand the stress
dysplasia occurs when theres an abnormality in maturation of cells within a tissue or cells are irregular in size and shape and disorderly in organization
What are the irreversible proliferation of disorderly cells of neoplasia?
Benign or malignant neoplasias
Benign: cells are WELL DIFFERENTIATED, near normal structure, and NORMAL FUNCTION OR HYPERFUNCTION, grow cohesive expansile masses that remain localized and usually encapsulated and may press agains body structures
Malignant: cells WIDE RANGE from well differentiated to undifferentiated, pleomorphic (cells and nuclei display variation in size and shape from their neighbors), cells lose normal polarity, higher rate of replication, do not respond normal to controls, evasion of immune system, loss of cell to cell adhesion, and exhibit anchorage independence which allows them to metastasize; HYPER OR HYPO OR ODD FUNCTIONING; hyper chromatic nuclei
How are malignant cells invasive?
infiltrate and destroy surrounding tissue by securing and enhancing proteolytic enzymes
poorly demarcated from surrounding tissue
lacking well defined cleavage plane
What do all tumors have?
parenchyma (made up of transformed or neoplastic cells
stroma (it is the supporting, host-derived, non neoplastic, made up of connective tissue, blood vessels, and hot-derived inflammatory cells)
What does anaplasia mean?
lack differentiation and is considered hallmark of malignancy
What are some carcinogenic factors that increase risk of malignant neoplasia?
environmental chemicals: produce free radicals and cause tissue injury; dose dependent
radiation
viruses: cause transformation by a mechanism called insertional mutagensis (the viral genes are incorporated into the host’s genome at specific sites and cause cell transformation
during some viral infections, the host’s immune system can become compromised, allowing neoplastic cells to emerge that would otherwise be rejected
What are some host factors that would contribute to increase risk of malignant neoplasia?
inherited predisposition (inheritance of a single mutant gene)
familial predisposition (familial clustering of cases but role of inheritance unclear)
age, gender, immune system function
The genes whose functions are relevant to tumor cells
tumor supressor genes (protect cell from developing into cancer cell); include proteins involved in DNA damage control, cell cycle control, programmed cell death, and cell adhesion
(Think tumor suppressor genes=checks and balances with DNA, cell cycles/death)(prevent growth)
proto-oncogene (they promote normal cell growth and differentiation); include proteins involved in various steps of the extracellular growth factor signaling pathway from the membrane receptors to the membrane intermediates to the proteins mediating the cytoplasmic signaling cascades
(Think proto-oncogene=cell growth)(help growth)
What occurs molecularly during abnormal cell growth or cancer?
there is a genetic alteration/mutation or amplification that causes malfunction of these genes
What happens when there is an error with the pro to-oncogene?
the cell will divide uncontrolled;
1 mutations in the proto-oncogene can encode growth factors (acquire growth factor self-sufficiency and/or over expression of growth factors)
2 can encode growth receptors(acquire mutant receptors that deliver continuous mitogenic signals to the cell) (over expression of normal growth factor receptors=always turned on and do not need binding)
3 can mimic function of normal cytoplasmic signal-transducing proteins (those in the inner leaflet of the plasma membrane and transmit to nucleus{raw protein is the most common} this activates a signal that eventually tells the cell to grow or divide but this signal cannot be deactivated) (also non-receptor associated tyrosine kinases that act in the growth promoting pathway and pathways that control cell growth cannot be deactivated)
4 encode nuclear transcription factors in the nucleus (mutated transcription factors bind to DNA that activate transcription and tell the cell to divide)
5 dysregulate the activity of the cyclins and cyclin-dependent kinases (favor cell proliferation/growth)
What are the proteins associated with proto-oncogene mutations that cause the cell to grow/divid uncontrolled?
ras protein and tyrosin kinases
What happens when there is a mutation in the tumor suppressor genes that cause the cell to continuously transform?
alterations/inactivation of tumor suppressor genes allow for continuous cell transformation (favors growth and proliferation as well as malignant potential)
P53 is the most commonly mutated gene (cell quiescence=temporary cell cycle arrest) (stimulates DNA repair pathways) (cell senescence=permanent cell cycle arrest) (triggers apoptosis)
What is the most commonly mutated tumor suppressor gene?
P53
What happens when there is a mutation or alteration with both the proto-oncogene and tumor suppressor gene?
further anapestic changes because cells do not have time to repair DNA damage
promotes growth of undifferentiated cells
tumor grows to point that center becomes hypoxic (natural selection of more aggressive tumor cells that are resistant to hypoxia and toxins){more chances for mutations that allow them to survive hypoxia and toxins}
What happens when there is a defect in DNA repair genes?
promotes cell division of defective cells (neoplastic cells emerge)
