Tumor Growth & Progression Flashcards
What is a psr?
Probability of self renewal in a cell population scaled from 0.00 (0%) - 1.00 (100%)
What does a psr of 0.50 indicate?
Stable cell population
What does a psr of 0.52 indicate?
malignancy
What does a psr of 0.49 indicate?
Slow decline & decay of a tissue cell # that will eventually shrink and disappear
What is the goal of cancer treatment in regards to psr?
To get the psr of the neoplastic cells below 0.50
What is a tumor growth fraction?
Ratio of cell proliferation to cell loss
What are the factors that influence tumor growth?
tumor angiogenesis:
- Oxygen and nutrient supply
- Metastasis
- Tumor size
- growth factors (VEGF and FGF) & inhibitors (p53?)
What is the purpose of angiostatin?
To stop blood vessel growth and supply to tumors
What is vascular endothelial growth factor?
Growth factor that gives a tumor the ability to undergo angiogenesis and gain capillaries and a blood supply
What is fibroblast growth factor?
Growth factor that gives a tumor a connective tissue stroma for support
What are the general steps (cellular basis) of metastasis of carcinomas?
- Detachment via loss of cadherin molecules
- Attachment to basement membrane/ECM with laminin and fibronectin
- Secretion of proteolytic enzymes (protease) to degrade ECM
- Movement of tumor cells through BM into vessels via cytokines (autocrine motility factor)
What is tumor progression?
The orderly progression from a preneoplastic lesion to a benign tumor and ultimately an invasive cancer
What cancer is the exception to normal tumor progression?
Colon carcinoma
What is important about genetic instability in regards to neoplasms?
Increased rate of random, spontaneous mutations during clonal expansion will increase chances of developing a neoplasm
What molecule is lost when a tumor cell detaches and attempts to metastasize?
Cadherin
What molecules are expressed when a tumor cell that has detached from the primary tumor tries to attach to the basement membrane of a distant tissue?
Laminin and fibronectin
What enzyme is primarily expressed by a metastatic tumor cell that has spread to a distant tissue that degrades the ECM of that tissue?
Matrix metalloproteases
What cytokine allows for movement of tumor cells through the basement membrane and into vessels?
Autocrine motility factor
(carrot for the horse)
What are the most common sites for metastasis of malignant neoplasms?
Liver
Lung
Bone
Brain
What is the most common site for metastasis in the body?
Lung
What is organ tropism?
Neoplastic cells preference to have a selective site for metastasis that cannot be explained by natural pathways of drainage
What is the metastatic pattern of lung carcinoma?
Adrenal Glands (#1) and brain
prostate carcinomas metastasize to ____
bone
Most tumors elicit a ____ inflammatory response?
Chronic
What are genetically identical mice in animal lab studies called?
Syngeneic mice
What are the four sub-experiments conducted on mice that led to the theory that the body has natural defenses against cancer cells?
- Mice injected with cancer/oncogene to prove oncogenic effect (malignant tumor develops)
- tumor excised from mouse–> tumor cells injected into syngeneic mice -> tumor develops
- in untreated mice, tumor metastasizes & kills mice
- when reinjected into original treated mice, mouse rejects tumor & survives (developed immunity)
What do mouse experiments with tumor injections demonstrate in regards to our immune system?
Our body has immune responses and defenses to oncogens (immunosurveillance; does NOT tell us why/how)
What is the upper limit of tumor burden for malignancy?
1 Kg or 10^12 (One trillion) tumor cells
What is the lower limit of clinical detection for tumors?
1 cm^3 or 10^9 (One billion) tumor cells
At diagnosis, approximately ____ of all cancer patients are already metastatic
1/2
What is tumor immunosurveillance?
Recognition and destruction of tumor cells by the immune system
What is a tumor specific antigen?
Cell surface molecule produced ONLY by tumor cells
What is a tumor associated antigen (TAA)?
Normal molecule made by normal tissues that are increased with tumors
What is an example of a tumor associated antigen (TAA)?
Prostate specific antigen (PSA) expressed in prostate adenocarcinoma
What are natural killer cells?
Lymphocyte-activated killer cells that can lyse tumor cells without recognizing TSA
What cytokine activates natural killer cells?
IL-1
What are cytotoxic CD8+ T lymphocytes?
lymphocytes that recognize TSAs and lyse tumor cells
Cytotoxic T lymphocytes require the presence of __________ to lyse a tumor cell
Tumor specific antigen (TSA)
What do patients with leukemia often die of?
Anemia or systemic infection due to a weakened immune system
When does a tumor cell require its own blood supply?
10^6 or 1 million cells
What white blood cells aid in tumor immunity?
CD8+ cytotoxic T lymphocytes and NK cells
