Neoplasia 2 Flashcards
(24 cards)
Two enabling factors of malignancy
Tumor promoting inflammation and genomic instability (mutator phenotype)
Examples of tumor suppressor genes
Rb, p52, TGF β, APC
These send proliferating cells to enter G0
How do tumors evade apoptosis?
Usually by the lost of p53 function that cause over expression of MDM2 which is a p53 inhibitor
What is BCL2?
Anti-apoptotic member
Explain the mechanism of how tumor cells have limitless replciative potential (telomeres)
Tumor cells deactivate telomerase and thus telomeres do not shorten after replication and thus allowing for limitless replicative potential
Metabolism of cancer cells
Warburg metabolism where they favor glycolysis over oxidative phosphorylation
Some ocoproteins (products of mutated oncogenes) causes formation of high levels of abonromal metabolites that leads to \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_? Give an example of a metabolite
Epigenetic changes and oncogenic gene expression
Ex. Mutated isocitrate dehydrogenase (IDH)
Tumor cells can activate and influence stromal cells.
How are stromal cells changed to allow for tumor cell invasion and metastasis?
Proteases remodel the ECM and TGF β promotes epithelial mesenchymal transition (EMT)
Genetic component of HNPCC
Micro satellite instability characterized by changes in length of short tandem repeating sequences
Xeroderma pigmentosum have a defect in ____________ (genetics)
Nucleotide excision repair pathway
Tumors with high/low growth fractions are susceptible to chemotherapy
High;
Growth fraction: # of cycling cells / # of total cells
In tumor cells there is more cells in the proliferative/nonproliferative pool in the cell cycle
Proliferative;
Normal cells you will see more of them in the non proliferative pool
Sub populations of tumors may vary in:
Antigenicity, invasiveness, metastatic potential, and growth factor requirement
Phases of metastasis
- Invasion of ECM
- Spread into the interstitial tissue
- Hematogenous spread and tumor homing
How do tumor cells detach and degrade ECM proteins
Detach Bria ↓ Catherine’s
Degrade via colagenase and Cathepsin B
The homing (metastatic site) of tumors is related to:
- presence of absence of specific molecules
- chemokines
- unfavorable environment like the muscle
Examples of tumor antigens for tumor immunity
- Products of mutated oncogenes and tumor suppressor genes such as RAS, BCR-ABL
- overexpressed cellular proteins such as PSA
- antigens produced by viruses
- oncofetal antigens such as CEA
- ## altered cell surface protein CA125, CA19.0
Tumors with high/low infiltrating lymphotes (CTL and TH1 cells) have a better prognosis
High
How do tumor cells breakdown the immulogical barrier?
Production of proteins that inhibit CTL’s, antigenic modulation and outgrowth of antigen negative clones
Therapy involving CLTA4
Using an inhibitor antibody for CLTA4 allows CD8 T cells to engage B7 coreceptors and thus activate T cells
Immunotherapy involving program cell death ligand
Using an anti-PD1 ligand can lead to activation of CTL which kill the tumor cells
Describe grade of a tumor
Level of differentiation and is particular tot he tumor
Based on differentiation, mitosis and necrosis
What is the stage of a tumor
Extent of spread
Usually more important than grade
Explain the TNM categories in staging a tumor
T: size of tumor
N: extent of spread to regional lymph nodes
M: metastases (presence or absence)
