Signal Transduction III Flashcards
How does overexpression occur?
At the mRNA or protein level:
DNA amplification
Increased transcription
decreased degradation
What usually causes constitutive activation
mutation (but NOT always)
The paradigm of protein over expression = sensitivity to inhibitor
NOT very general
Colon Cancer
4th most commonly diagnosed cancer
Second most lethal cancer
Universally accepted to screen
Chemotherapy for Colon Cancer
Metastatic : 5-fluorouracil with either irinotecan or oxaliplatin
EGFR
driver of proliferation and survival
Ras and Raf
downstream of EGFR - leads to cascade and transcription.
What does EGFR activation cause?
Cell survival Proliferation Angiogenesis Metastasis Cell motility
EGFR antibodies
Cetaximab (first used, not anymore, Martha Stewart)
Panitumumab
What is Panitumumab active in?
Colon cancer
Squamous cancers of head and neck
Squamous (HPV driven) cancers of the cervix and penis
EGFR in lung cancer
deletion on chromosome 19 or 20, mutation on receptor
EGFR in colon cancer
NOT a receptor mutation
When do blocking EGFR antibodies work?
When cells have wild type Ras/Raf
What is the most common leukemia?
Chronic lymphocytic leukemia (CLL)
CLL is a disease of ______, not ________.
accumulation, over-proliferation
SLL and CLL
same disease
What does it mean when K67 is elevated?
cell cycling is active
in nucleus proportional to cell cycling activity
What does % of K67 mean?
What percentage of cells are in active cell cycling
Bcl-2
anti-apoptotic
Bax
pro-apoptotic
Low Bax/Bcl-2
low apoptosis (anti-apoptotic ratio)
High Bax/Bcl-2
high apoptosis (pro-apoptotic ratio)
What does CLL present with?
Commonly with autoimmune phenomena including:
- Immune thrombocytopenic purpura (ITP)
- Auto immune hemolytic anemia (AIHA)
- Auto immune agranulocytosis
What else do patients with CLL have?
typically hypogammaglobulinemia
virulent infections
