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What are stromal cells?
support cells in the tissue (CT, BV, etc)
What are parenchymal cells?
- uniquely adapted to perform the fxn of an organ
- Ex: parenchymal cells of heart are cardiomyocytes; of liver are hepatocytes
What are mesenchymal cells?
cells of mesodermal or neural crest origin that give rise to CT, blood, and muscle
What is an oma?
What is a carcinoma?
malignant tumor of epithelial origin
What is a sarcoma?
malignant tumor of mesenchymal origin
What is the cancer stage is M=1?
every cancer is stage IV if M=1
- no penetration of basement membrane by the tumor
- Ex: polyp growing but has not grown into basement membrane
tumor has grown through basement membrane, but is still local
invasion of tumor into other organs/neighboring tissue
Four ways cancer can spread.
- Direct (right out of local site)
- Thru lymph nodes
- Thru blood
- Thru incisions (biopsy, surgery)
What is leiomyoma? leiomyosarcoma?
- beinign tumor of smooth muscle
- malignant tumor of smooth muscle
What does well-differentiated mean?
- In a benign tumor, for example, it looks like the cells from which it came.
- Myoma looks like myocytes; melanoma looks like melanocytes
Six things ("super powers") that a cell needs to become cancerous.
- Self-sufficiency in growth signals (accelerator)
- Insensitivity to anti-growth signals (brake)
- Evade apoptosis (ignore the signal)
- Sustained angiogenesis
- Limitless replicative potential (turns on telomerase)
- Tissue invasion and metastasis
What is a proto-oncogene?
- normal gene w/ normal function
- a protein whose normal cellular gene can be converted into a cancer-promoting oncogene by mutation
How many mutations are needed in a proto-oncogene to make it cancerous?
Examples of proto-oncogene mutations.
- bcl-2: B-cell Lymphoma
- HER2/neu (erbB-2): Breast or ovarian cancer & others (epidermal growth factor Receptor)
- N-myc: Neuroblastoma
- C-myc: Burkitt lymphoma, others
- **Ras - various, 20-30% of ALL cancers**
Two things that can happen with chromosomal translocations.
- Too much protein
- Synthesis of a Novel Fusion protein (a new protein is produced that did not exist, or did exist and causes cancer)
Examples of Tumor Suppressor Genes.
- p53: various
- BRCA1, BRCA2: breast and ovarian (BReast CAncer)
- APC: colorectal (Adenomatous Polyposis Coli)
- RB1: various (RetinoBlastoma)
- MSH2: colorectal, endometrial, gastric
- NF1, NF2: neuroblastoma, etc. (neurofibromin)
What is a germline mutation?
A baby is born with one already mutated tumor suppressor gene
Proto-oncogenes _____ a function and need _____ how many mutations to do this?
Tumor Suppressor Genes _____ function and need how many mutations to do this?
What can happen when cancer gets into the blood?
It can travel through the blood and land on a distant organ, colonize it, and cause a secondary cancer site
How can cancer spread through surgery?
The scalpel can drag cancer cells into neighboring tissue
How does a cancer cell develop limitless replicative potential?
turns on telomerase, which keeps the telomeres from getting too short and signaling the cell to stop growing
B-cell Lymphoma proto-oncogene mutation
HER2/neu (erbB-2) mutation
Breast or Ovarian cancer proto-oncogene mutation
Neuroblastoma proto-oncogene mutation
Burkitt Lymphoma proto-oncogene mutation
- proto-oncogene mutation
- 20-30% of ALL cancers
Tumor Suppressor Gene mutation for various cancers
BRCA1, BRCA2 mutation
- Tumor Suppressor Gene mutation for BReast and ovarian CAncers
- BRCA1 is the DNA repair molecule
Tumor Suppressor Gene mutation for colorectal cancer (Adenomatous Polyposis Coli)
Tumor Suppressor Gene mutation for colorectal, endometrial, & gastric cancers
NF-1, NF-2 mutation
Tumor Suppressor Gene mutation for Neuroblastoma (neurofibromin)
_____ is one of several targets of the activated RAS pathway.
How does RB play a role in cancer?
- RB (retinoblastoma gene) is a protein assoc with checkpt b/w G1 & S where DNA is REPLICATED.
- It sends anti-growth signals if it finds a bad cell. If BOTH RB genes are missing or bad, this checkpoint is lost.
- Now the bad cell can continue to grow.
What is the job of P53?
- Tumor Suppressor Gene
- activates processes to repair defective DNA
- stops cell cycle until DNA is repaired
- if repair fails, apoptosis is triggered
How does P53 play a role in cancer?
- If BOTH P53 genes are bad, there is no checkpoint to stop bad DNA from continuing through the cell cycle
- defective DNA can then become cancer
What size tumor can cause death?
How is sustained angiogenesis triggered?
- Vascular Endothelial Growth Factor (VEGF) is secreted by the tumor
- VEGF triggers BV to grow in tumor
How is the limitless replicative potential turned on for a tumor?
It turns on telomerase to prevent shortening of telomeres
What are the steps a cancer cell takes to escape it's parent tissue and migrate?
- Loosens junctions
- breaks down collagenase to dissolve the basement membrane
- attaches to something below the basement membrane (like fibronectin) & pulls itself away
- migrates to CT below epithelial cells
What are the main sites of metastatic tumors?
- lungs (most popular)
- liver (common w/ GI cancers)
What is the function of viral protein E7?
disables the Rb protein, which means a checkpoint is lost; causes increased rate of mutated cell accumulation
What is the function of viral protein 6?
neutralizes P53, inhibiting a checkpoint; causes increased rate of mutated cell accumulation
Other tissues affected by chemotherapy that contain rapidly dividing cells.
- GI Tract (esp sm intestine)
- Bone Marrow (anemia, neutropenia)
- Hair follicles (mostly head)
- Skin (thin skin, rashes)
What makes up plasma?
- 90% water
- 10% solutes.
- Of the solutes: ~7% are plasma proteins made in the liver; ~3% are electrolytes, gases, nutrients, waste, & hormones
Of what are the plasma proteins made? What are their fxns?
albumin (60%): oncotic pressure, carrier molecule
What is the function of alpha & beta globulins?
carrier proteins for lipids & fat-soluble vitamins
Where are gamma globulins/antibodies made?
in lymph node or other lymph organs
The 3 main plasma proteins.
What type of WBCs will be elevated with type I hypersensitivity rxns?
Which types of RBCs are granulocytes?
- (also mast cells)
Function of mast cells.
cause vascular permeability & smooth muscle cell contraction
What are granulocytes?
- tiny membrane-bound granules filled with:
- digestive enzymes (kill microorganisms) &
- biochemical mediators (inflammation & immunity)
What is the main function of agranulocytes?
create immunity (lymphocytes)
WHich cells are agranulocytes?
- lymphocytes (B-, T-, & NK-cells)
Function of NK-cells.
provide immunity against virus-infected and tumor cells w/o prior exposure to antigens
Additional stores of platelets are where?
in the spleen
Secondary lymph organs.
- lymph nodes
- Peyer's Patches on sm intestine
What happens in the white splenic pulp?
lymphocytes illicit an immune response to blood-borne pathogens
What happens in the red splenic pulp?
- It is the primary filtration site
- macrophages phagocytose old damaged RBCs
- Heme (iron) is recycled
What is differentiation when referring to hematopoiesis?
maturation of blood cells
Two types of tissue in BM.
- Red (active) - hematopoietic tissue
- Yellow (inactive) - adipose tissue
Three ways hempatopoiesis is accelerated.
- EPO causes increased amounts of active marrow (yellow to red)
- increased rate of differetiation of daughter cells
- increased rate of proliferation of blood cells
What is GM-CSF?
- Granulocyte Macrophage Colony Stimulating Factor: released from:
- T-cells, endothelial cells, & fibroblasts
- leads to formation of myeloid progenitor cells
- become either granulocyte OR macrophage