[1] Basic Neoplasia Flashcards
Father of Medicine
Hippocrates
Thought pathophysiology of cancer was due to the imbalance of the 4 humors
Galen
Came up with the Cellular Theory of Disease
Rudolf Virchow
6 Components of Malignancy
- Sustained ability to proliferate
- Ability to evade growth suppressing controls
- Ability to evade cellular death
- Capacity to unlimited replication and immortality
- Ability to produce their own blood supply
- Capacity to invade and metastasize
Function: Oncogenes
Promote cell proliferation through growth and division
Oncogenes cause cancer to manifest when they are “on” or “off”?
Activation of even just one gene in a pair will cause cancer to manifest
Oncogenes reside in the body as?
Proto-oncogenes
Bladder CA results from what gene mutation?
Point Mutation in the HRAS Gene (Protein: Glycine -> Valine)
Function: NF2 Gene
Contact inhibition
Function: LKB1 Gene
Epithelial polarity protein that enhances epithelial structure and maintains tissue integrity
Proto-oncogenes with a gain/loss of function would result in cancer?
Gain of Function
TS Genes with a gain/loss of function would result in cancer?
Loss of Function
Mutator Genes with a gain/loss of function would result in cancer?
Loss of Function
Function: p21
Inhibits cell cycle progression and permits DNA repair to take place
Function: p53
Proofreader of DNA
DNA damage would result in the halting of the cell cycle for repair or apoptosis in cases of severe DNA Damage
Mutations in what gene are the most common genetic alterations found in human cancer
p53 Gene
Anti-Apoptotic Genes (2)
BCL-2
BCL-xL
Pro-Apoptotic Genes (4)
BAX
BAD
BAK
BID
Non-hodgkin’s Lymphoma evades cell death very effectively through this method
Overexpression of BCL-2 causing the absence of apoptotic signals
How do tumor cells proliferate using autophagy?
Condition induced by nutrient deficiency causing them to recycle their organelles allowing them to survive until a blood source comes in
How do tumor cells proliferate using necrosis?
Recruitment of inflammatory cells that may be tumor-promoting
Define: Hayflick Limit
Number of times a normal human cell will divide until cell division stops
DNA Sequence of a Telomere
TTAGGG
What is a Telomerase
Ribonucleoprotein enzyme which preserves the itnegrity of telomeres
Define: Nowell’s Hypothesis
Eventual mutations that will over time become a malignancy
3 Major Features of Invasion
- Cell adhesion to basement membrane
- Local proteolysis of the membrane by matrix metalloproteinases (MMPs)
- Movement of the cell through the rent in the membrane and the extracellular matrix
2 pack a day smoking leads to how much increased risk of esophageal cancer
7-8x Risk
What is the most carcinogenic substance produced by man
Tobacco
Most notorious dust one can encounter
Asbestos
Vinyl chloride is notorious for causing?
Angiosarcoma
Carbon tetrachloride and benzene can cause what kind of cancer?
Leukemia
Lymphoma
Define: Missense mutation
Formation of an abnormal protein that may be different than the one intended
Define: Nonsense mutation
Point mutations that result in a premature “stop” sequence
Are exons or introns noncoding regions?
Introns are noncoding regions that are removed before mature mRNA is complete
A Philadelphia chromosome is a result of?
Translocation of abl from Chromosome 9 to the long arm of Chromosome 22
The Her2 gene causes breast cancer in 30% of cases via what mechanism?
Gene Amplification
Do tumor suppressor genes have a dominant or recessive type of activation?
Recessive, you would need to destroy both pairs to deactivate tumor suppression
First Tumor Suppressor gene discovered
RB Gene
This family of proteins are involved in DNA Repair
MSH Family
Is apoptosis a Type 1 or Type 2 Cell Death?
Type 1
Is autophagy a Type 1 or Type 2 Cell Death?
Type 2
Function in Tumor Angiogenesis: Pericytes
Support and maintenance of tumor vasculature
Hallmark of Malignant Cancer
Ability to invade and metastasize
Two Processes of Metastasis before Clinically Detectable Disease
- E-cadherin Inactivation
- Anchors cells and provide cell-cell adhesion. Inactivation means cells no longer need neighboring cells to survive and proliferate - Elaboration of Proteases
- Allows transportation of cells (Proteases break basement membranes)
Cancer cells usually transition from what kind of cell to what kind of cell
Epithelial -> Mesenchymal Transition
Most Malignant Type of Tumor Spread
Hematologic Invasion
Tumor cells have this difference with normal cells when it comes to energy metabolism
Increased glycolysis and preference to using lactic acid energy instead of oxygen even when oxygen supply is adequate
Number one cause of death and treatment failure in Oncology
Metastasis
Shortest Phase of the Cell Cycle
M Phase
Phase where DNA Replication Occurs
S Phase
Protein that tells the cell it is okay to go from one phase to the next
Cyclin-dependent Kinases (CdKs)
The G2/M Checkpoint is regulated by?
Cyclin B/cdc2
Most important cell checkpoint during mitosis
G1/S Checkpoint
S-phase will not continue unless this gene is stimulated
Rb Gene
Rb gene is inhibited by? It is tightly controlled by?
Inhibited by Cdk4
Tightly controlled by p16
