Pathology- General Principles Flashcards
Ionizing radiation causes cell damage through what 2 primary mechanisms?
1) DNA double-strand breakage
2) Generation of reactive oxygen species
What type of activating mutation is resistant to anti-EGFR agents (monoclonal antibodies like cetuximab and panitumumab which block EGFT)?
KRAS-activating mutations are resistant to anti-EGFR as they have constitutive activation of a downstream signal that is independent of EGFR stimulation or blockade.
High levels of aflatoxin (from Aspergillus fungi, can be found in “moldy” grains in some regions of china) can lead to what cancer?
Hepatocellular carcinoma
Gene product of HER2/neu?
Receptor tyrosine kinase
- HER2/neu is an oncogene which accelerates cell proliferation
- Can lead to breast and gastric carcinomas
- Worse prognosis
The presence of ______ increases the ESR (erythrocyte sedimentation rate) which will look like rouleaux formation that settles at the bottom of the tube?
Acute phase reactants
- C-reactive protein (CRP)
- Serum Amyloid A (SAA)
- Fibrinogen
- Ceruloplasmin
- Haptoglobin
The presence of pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) stimulates the liver to release acute-phase reactants which increases the ESR, a nonspecific marker for inflammation.
Adenoma-Carcinoma Sequence
- APC inactivation (normal colon—> hyperproliferative epithelium)
- K-ras activation (hyperproliferative epithelium—> adenoma)
- P-53 inactivation (adenoma—> carcinoma)
Tumor suppressor genes responsible for regulating cell cycle progression by preventing the transition from the G1 phase to the S phase?
-RB
(active when dephosphorylated)
(phosphorylation will deactivate it and lead to tumor progression)
Antioxidant enzymes that convert ROS to oxygen and water, therefore neutralizing their capacity for cellular damage?
- Superoxide Dismutase
- Glutathione peroxidase
- Catalase
1st phase of wound healing
Hemostasis (0 hours-1 day)
- vasoconstriction - Fibrin Clot Formation
*Platelets
2nd phase of wound healing
Inflammation (3 hours-5 days)
- Vasodilation
- Increased permeability
- Inflammatory cell chemotaxix (Cellular infiltration)
*Macrophages
3rd phase of wound healing
Proliferation (3 days- 5 weeks)
- Reepithelialization
- Neovascularization (angiogenesis)
- Collagen production
*Fibroblasts
4th phase of wound healing
Remodeling (3 weeks- 2 years)
-Reorganization and cross-linking of collagen (Type 3–>Type 1)
*Matrix Metalloproteinases
BRCA1/2 are what type of genes? Mutation leads to what cancers?
Tumor Suppressor (DNA repair genes)
Breast & Ovarian Cancer
RAS is what kind of gene? Leads to what?
Oncogene (GTP-binding protein)
Cholangiocarcinoma
Pancreatic Adenocarcinoma
BRAF is what kind of gene? Leads to what?
Oncogene (RAS singnaling transduction)
Hairy cell Leukemia
Melanoma
VHL is what kind of gene? Leads to what?
Tumor suppressor (Ubiquitin ligase component)
Renal cell carcinoma
Von Hippel-Lindau Syndrome
RB is what kind of gene? Leads to what?
Tumor Suppressor (G1/S transition inhibitor)
Retinoblastoma
Osteosarcoma
ABL is what kind of gene? Leads to what?
Oncogene (Nonreceptor tyrosine kinase)
Chronic Myelogenous Leukemia
ERBB2 (HER2) is what gene? Leads to what?
Oncogene (Receptor Tyrosine Kinase)
Breast Cancer
ERBB1 (EGFR) is what type of gene? Leads to what?
Oncogene (Receptor tyrosine kinase)
Lung adenocarcinoma
MYC is what kind of gene? Leads to what?
Oncogene (transcription factor)
Burkitt Lymphoma
APC/B-catenin is what kind of gene? Leads to what?
Tumor suppressor (WNT signaling pathway)
Colon, gastric, & pancreatic cancers
Familial adenomatous polyposis
6 Common Hereditary Cancer Syndromes (They are all Autosomal Dominant)
Lynch Syndrome—>MSH2, MLH1, MSH6, PMS2
Familial Adenomatous Polyposis—> APC
von Hippel-Lindau Syndrome—> VHL
Li-Fraumeni Syndrome—> TP53
MEN1–> MEN1 (Parathyroid, Pituitary, Pancreatic)
MEN2–> RET (Medullary thyroid, Pheochromocytoma, Parathyroid)
Function of metalloproteinases?
They are zinc-containing enzymes which:
- degrade the extracellular matrix
- participate in normal tissue remodeling
- participate in tumor invasion through the basement membrane and connective tissue
