Tumor Growth and Immune Response Flashcards
What is the natural history of malignant tumors?
Malignant change as a result of genetic mutations –>
Proliferation of the malignant cells with further mutations –>
Invasion of neoplastic cells –>
Distant metastases
What is the growth fraction?
Ratio of cell proliferation to cell loss
Has implications in cancer therapy
What is psr?
Probability of self renewal
p= 0.00-1.00
A stable tissue has what psr?
0.50 psr
With no death and a slow increase and growth of cell numbers, what is the psr?
0.52 psr
Cells eventually do robbery
With a slow decline and decay of cell numbers, what is the psr?
0.49 psr
Cells eventually disappear
Which tumors do not induce angiogenesis?
Young tumors
What is the focus of current research on tumor angiogenesis?
Angiostatin/immunotherapy to starve tumor, prevent growth, and lower metastasis
What is VEGF and FGF?
Vascular endothelial growth factor and fibroblast growth factor
What inhibits angiogenesis?
P53
Tumor angiogenesis has roles in…
- oxygen and nutrient supply
- distant spreading of neoplastic cells
In the cellular basis of metastasis of carcinomas, what happens first?
Detachment of tumor cells from each other: loss of cadherin (cell-adhesion) molecules
In the cellular basis of metastasis of carcinomas, what happens after detachment of tumor cells from each other?
Attachment of tumor cells to basement membrane/ECM (laminin, fibronectin)
In the cellular basis of metastasis of carcinomas, what happens after attachment of tumor cells to the basement membrane/ECM?
Secretion of proteolytic enzymes which degrade ECM (matrix matalloproteases)
Matrix metalloproteases degrade the ECM
What is this dependent on?
Iron/zinc
In the cellular basis of metastasis of carcinomas, what happens after proteolytic enzymes degrade ECM?
Movement of tumor cells through bone marrow and into vessels
Once proteolytic enzymes degrade ECM, how do tumor cells move through bone marrow and into vessels?
Locomotion via cytokines (autocrine motility factor)
What is a metaphor for autocrine motility factor?
Breadcrumb trail moves away from location
What is tumor progression?
Orderly progression from pre-neoplastic lesion to benign tumor to, ultimately, invasive cancer
What is the effect of genetic instability?
Yields an increased rate of random, spontaneous mutations during clonal expansion
A growing tumor tends to be selected for its…
potential for survival, growth, invasion, and metastasis
What are the four most common sites for metastatic dissemination of malignant cells?
- Liver
- Lung
- Bone
- Brain
All have huge blood supply
What is the most common metastatic site for colon cancer?
Liver
What is the most common metastatic target?
Lung
What is organ tropism?
Neoplastic cells may have a selective site for metastasis that cannot be explained by natural pathways of drainage; preferential spread
Where does lung carcinoma preferentially spread?
Adrenals and brain
Where does prostate carcinoma preferentially spread?
Bone
What are possible causes of organ tropism?
- Tumor cell adhesion molecules
- Secretion of chemoattractants by target organs
Most tumors elicit a ___ inflammatory response
chronic
Inflammation is correlated with better prognosis for ___ cancers
some
Do immune defenses against tumor cells exist?
Yes
What is the significance of animal studies such as re-implantation of non-metastatic tumor in mice?
Suggests tumor immunity exists
What is immunosurveillance?
Recognition and destruction of tumor cells by the immune system
What are tumor specific antigens (TSAs)?
Molecules that only tumors will produce; very few exist
What are tumor-associated antigens (TAAs)?
Molecules that normal tissues make, but make more of with neoplasia
What is an example of a TSA?
Mage (melanoma antigen)
What is an example of a TAA?
PSA (prostate specific, everyone has some)
Can females get prostate cancer?
Yes
What are the capabilities of natural killer (NK) cells?
Can lyse tumor cells without recognizing TSA
What are the capabilities of cytotoxic T cells?
Recognize TSAs and lyse tumor cells
In immunodeficient hosts, there is an ___ frequency of cancer
increased
What are three ways immunosurveillance can break down when cancer arises in an otherwise healthy individual?
- Selective loss of strong TSAs
- Carcinogens or tumor products may suppress immune response
- Tumor cells may kill immune cells
Do tumor cells or normal cells reproduce faster?
Tumor cells reproduce faster than normal cells
