review of neoplasia and immunology of cancer - lecture notes - julia Flashcards
what are the three stages of carcinogenesis?
- initiation - provides genetically altered cells
- promotion - stimulates clonal expansion of intiated cells
- progression - reflects additional genetic and phenotypic changes required for malignancy
what occurs during the promotion stage of carcinogenesis? (what allows for growth?)
- initiated cells are dependent on normal pathways to stimulate growth (clonal expansion)
- exogenous stimuli are substituting for an additional mutation that would confer autonomous control of growth (eg loss of a tumor suppressor gene)
what occurs during the progression stage of carcinogenesis?
- occurs with the stepwise addition of genetic changes/mutations
- confer additional features of the neoplastic phenotype and malignant phenotype
- examples
- angiogenesis
- expression of enzymes that destroy the basement membrane
- expression of telomerase
- evasion of apoptosis
what aspects of inflammation lead to carcinogenesis?
- generation of ROS - nonspecific damagers of proteins and nucleic acids
- increased cell death and turnover => more opportunity for mutations to appear
what inflammatory diseases have been found to be associated with causing cancers? (4)
- ulcerative colitis (autoimmune)
- hepatitis (viral, both B and C)
- chronic pancreatitis (hereditary and other)
- heliobacter pylori, peptic ulcer disease (1% progress to malignancy)
what kind of virus is hep C? (genome? reverse transcriptase?) what are the two hypotheses concerning how it increases risk for hepatocellular carcinoma?
- RNA virus without reverse transcriptase
- nonspecfic hypothesis:
- continuous inflammation and repair => increased cell division and generation of ROS
- specific hypothesis
- proteins transcribed from viral genome in infected cells interact with and inactivate protein products of cellular tumor suppressor genes, thus deregulating control of cell divisions
- true for both hep b and c - can find examples of such viral proteins
what is the evidence that the healthy immune system suppress the development of cancer by rejecting transformed cells? (3)
- transplant patients (immunosuppressed) are known to develop lymphomas and other kinds of cancer
- HIV patients develop Kaposi’s syndrome, non-hodgkins lymphoma, hodgkins disease, and other malignancies
- immune response decreases as you age and many cancers are more prevalent in the elderly
what are the origins of cancer that we’ve discussed? (4 - list)
- inherited or spontaneous mutation
- chemicals (carcinogens)
- radiation
- viruses
what are the characteristics of cancer that we’ve discussed? (5 - list)
- immortal
- invasive
- metastatic
- possess features of normal tissue counterpart from which it derives
- possess unique features different from the tissue from which it derives
what are the ways to prevent cancer? (3)
- avoid carcinogens, radiation, infection
- vaccination (such as for HPV)
- immune surveillance - immune system monitors for abnormal cells
what are some ways to treat cancer? (4)
- surgery
- chemotherapy
- radiation therapy
- immunotherapy
- targeted therapies such as glevec
what are some methods of immunotherapy used to treat cancer? (4)
- cytokines
- antibodies
- vaccination - developing vaccine after tumor is present to train the immune system to attack those cells
- cellular therapies
what is chromothrypsis? how is it different from the normal development of cancer?
- whole chromosome sort of explodes and comes back together
- only a minority of the cases of cancer
- the majority have one change after another that develop over many many years
describe the process of immunoediting (three steps to the presence of cancer)
- at first, the immune system can eliminate the mutated cells (tumor cells blue)
- at some point or in some foci, tumor underges more mutation and an equilibirum is established where the immune system is fighting off the tumor but the tumor is managing to modify itself to avoid destruction
- eventually these cells develop enough mutations that they escape immune survailance and become a tumor
how are NK cells involved in immunosuppresion of tumor?
- have a variety of specific pathways that help them recoginze and eliminate targets
- one potential way to exploit monoclonal antibodies would be to design them to coat tumor cells - the NK cells would then recognize these as targets
- can also recognize cells without class I MHC
- allows destruction of tumor cells that find a way to avoid killing by CD8 cells by turning off MHC production