Neoplasia Part 2 Flashcards
What are animal models used in cancer research? Why are these animals used? What percentage of people will perish from some sort of cancer?
Animal Models
• Experimentally-induced (Nude Mice) – able to accept grafting: no rejection (no only allografts but also xenografts -> tissue from other species) (No T lymphocytes -> lack thymus)
• Naturally occurring
• some stats of 20-25% of individuals will perish from some sort of cancer.
What are epigenetic changes? What else are seen in tumor cells aside from epigenetic changes?
Epigenetic changes: Refers to heritable changes in gene expression in somatic cells resulting from something other than a change in the DNA sequence (most common ones are DNA methylation and histone modification)”.
• DNA mutations, epigenetic changes & chromosomal alterations are also observed in tumor cells.
Some people have genetic predisposition to cancer
Epigenetic changes- No DNA damage but, molecular changes can alter some functions of the tumor.
What is carcinogenesis?
Carcinogenesis is a multistep process at both the phenotypic and genetic level -> tumor progression.
What occurs to normal cells that cause benign or preneoplastic lesions? What will cause them to potentially become malignant?
• In the presence of a promoter, these initated cells expand to form a preneoplastic lesion or benign tumor. With further genetic and epigenetic alterations, a malignant tumor emerges from a subclone of cells within the benign precursor lesion.
- Initiated cells have growth advantage against other cells if they are in the presence of a premotor.
- Formation of benign tumor can become malignant tumor. If it becomes one, it will have the ability to infiltrate surrounding tissue.
Can they cure the individual cancer genes?
No there are too many.
What are the 4 classes of normal regulatory genes that are the main targets of genetic damage and play a significant role in carcinogenesis? What happens if you lose repair cells?
- growth-promoting proto-oncogenes
- growth-inhibiting tumor suppressor genes
- genes that regulate programmed cell death (apoptosis), and
- genes involved in DNA repair
If you lose repair cells, you can have abnormalities printed in the genomes.
What is the p-53 gene? What does it do?
• p53 gene- cancer cop
◦ Growth inhibiting tumor supressor gene.
• Considered guardian of the genome.
What occurs to cells that have dna damage in the presence of P-53 and in the absence?
• Cell exposed to DNA damage -> activated p53 gene -> binds to DNA -> stops cell division until problem is correct/ DNA repaired so damaged cells do not proliferate.
• p21 and GADD45 -> mechanics of cell
◦ If repair fails then cell is normal, if not then apoptosis.
• BAX -> hitman (induces apoptosis)
Cell with loss or damage to P53 then the mutant cells will expand and continue mutating.
What are the 8 changes in cell
physiology that together determine malignant phenotype?
- Self-sufficiency in growth signals (continue to grow)
- Insensitivity to growth-inhibitory signals (dont respond to inhibitory signals)
- Evasion of apoptosis (can avoid apoptosis)
- Defects in DNA repair
- Limitless replicative potential
- Sustained angiogenesis
- Ability to invade and metastasize
- Ability to escape from immunity and rejection
IMPORTANT SLIDE TO GO OVER
What is the strongest argument for immune survailences role in cancer? Are the survailence mechanisms as effective as they should be?
- The increase incidence of cancer in immuno-suppressed people
and animals is the strongest argument for the existence of tumor
immune surveillance.
• Unfortunately tumor immune surveillance mechanisms are not as
effective as they should be. The reason is that tumor cells have the
capability to develop mechanisms to evade the immune system of
the immunocompetent host.
What are tumor antigens? What are the types? and What can they be used for?
• Tumor antigens:
– Tumor-specific antigens (presented by MHC molecules on surface, presented only on tumor cells)
– Tumor-associated antigens (presented on surface of tumor and nontumor cells)
• Tumor antigens can serve as the targets of effective immune
surveillance
• Tumor antigens can be used for diagnosis, monitoring or
immunotherapy
( you can design antibodies against these antigens)
What are the major cells involved in immune survailence for cancer cells? What are the main defense mechanism? Is humoral response also effective?
- CD8 + Cytotoxic T lymphocytes (CTLs) are the mayor immune defense mechanism against tumors.
- Natural killer cells (specific type of lymphocytes) and macrophages also play a role. Interferon-gamma (IFN-γ), a cytokine produced by T-cells and NK cells, is a potent activator of macrophages.
- Antibodies against tumor antigens are also part of the defense mechanisms of the host but there is little evidence that humoral immunity is effective against tumors.
What are the tumor antigens recognized by CTL or Cytotoxic T lymphocytes?
Tumor antigens recognized by CTLs:
• Product of oncogene or mutated tumor suppressor gene.
• Mutated self protein
• Overexpressed or aberrantly expressed self protein
• Oncovirus ( i.e feline leukemia)
What mechanisms can tumors use to evade the immune system?
Mechanisms by which tumors evade the immune system
• Failure to produce tumor antigen
• Mutation in MHC genes or genes needed for antigen processing
• Production of immunosuppressive proteins.
What are the macro environmental and microenvironmental causes of tumors?
- Macro-environmental (extrinsic) causes: e.g.: UV light, ionizing radiation, chemical carcinogens, oncoviruses. (Example: FELV cat with lymphoma-> lymphoma caused by FELV (oncovirus))
- 2.Micro-environmental (intrinsic) causes: e.g.: heritable genetic changes, byproducts of normal metabolism including reactive oxygen species.