Finals part II Flashcards
(40 cards)
TDP-43 mutation
-accumulation in cell body of neuron(95%)
normally in nucleus
SOD1 mutation
- Superoxide normally converted to water
- with mutation SOD1 cannot breakdown superoxide radicals
Treatment for ALS
RILUZOLE; increases uptake or clearance of glutamate from the synapse
Two characteristics of stem cells
1) unspecialized, indefinite self-renewal
2) can be induced to differentiate into specialized cells
3 types of stem cells
1) adult stem cells
2) embryonic stem cells(ES)
3) induced pluripotent stem cells(iPS)
Adult stem cells(somatic stem cells)
- give rise to limited number of specialized cells
- normally kept in Go phase of cell cycle until activated by environment
Embryonic stem cells(ES)
- pluripotent, taken from inner cell mass of blastocyst
- however there are issues with ES therapeutics due to immune rejection
Induced Pluripotent Stem cells(iPS)
- Pluripotent and easy to obtain
- use 4 transcription factors; oct 4, SOX2, Klf4, and c-Myc
- issue with c-Myc because it is oncogenic; caused 20% of mice to develop cancer
Percentage of cancer caused by somatic mutations?
90%
percentage of cancer caused by germline mutation(inherited)
5-10%
Ocogenes
- oncogenes result from gain of function mutation of proto-oncogenes
- they are always on
- receptor tyrosine kinases(RTKs)
Receptor Tyrosin Kinases(RTKs)
-misregulation could lead to cancerous growth
two examples
-dimerization of receptors causes it to be active without a binding ligand
-gene for RTK ligand always activated, independent of cell signal
Breast Cancer
- Human EGF Receptor-2(HER2) is a type of RTK
- 30% have amplified HER2 activity
Treatment of Breast Cancer
- HERCEPTIN; it’s a monoclonal antibody that attaches to HER2
- it tells body to target cancer cell
- it inhibits HER2 signaling
Clonal Evolution
-tumor develops through repeated round of mutation and proliferation giving rise to clone of fully malignant caner cell
Colorectal Caner
- by age 70, 50% of US adults have benign polyps; approx 10% of these develop cancer
- activation of Ras-Raf-Mek-Mrk-MAP Kinase Cascade is cause of 20% of reported colon cancer
ALS genetic factors
- SOD1(Cu/Zn SuperOxidase Dismutase)
- Defects in Chr 21; FUS/TDS, TDP-43
What kind of mutation in Tumor suppressors causes cancer?
Loss of function
what is the normal role of tumor suppressors ?
- Protect cells from becoming cancerous
- tell cell when to die
Two types of tumor suppressors
1) p53
2) Rb
What causes Leukemia?
- The Philadelphia chromosome which is a result of acrocentric translocation between chromosome 9 and 22
- this causes the fusion of Bcr and Abl genes
Fusion of Bcr and Abl genes..
- causes Bcr-Abl fusion protein
- Abl is normally a kinase, fusion causes it to be a super active kinase
Treatment for Leukemia
Gleevec; targets the Bcr-Abl fusion protein, blocking the ATP binding site. Lack of ATP blocks cell proliferation signaling
TDP-43 mutation
-accumulation in cell body of neuron(95%)
normally in nucleus
