Learning Objectives Flashcards
properties of malignant cancer cells
- unresponsive to normal signs of proliferation control
- de-differentiated
- invasive
- metastatic
- clonal origin (came from one cell)
- lack contact inhibition
- more glucose transport
- immortal
steps for carcinogenesis
- normal cell
- increased proliferation
- neoplasia
- carcinoma
- metastasis
cytogenetic abnormalities associated with malignancy
- chromosome translocation, deletion
- bringing a promoter near an oncogene
- interrupting transcription
retinoblastoma gene is on chromosome _____
13q14
retinoblastoma gene loss can be detected by ________________
PCR, Southern blot
RB is a ___________ gene
tumor-suppressor
APC encodes for a protein that regulates localization of ___________ protein
beta-catenin
When APC is lost, beta-catenin ________________
goes to nucleus to produce transcription of oncogenes
p53 is (homozygous/heterozygous) but a ___________________
heterozygous, tumor suppressor
adenovirus E18, HPV E6, etc. have __________ that inactivate _____
oncogenes, p53
v-src
phosphorylates tyrosine residues in other proteins
v-erb
mimics epidermal growth factor receptor
v-sis
mimics platelet-derived growth factor
Li-Fraumeni criteria
- proband with sarcoma diagnosed before age 45
- first degree relative with any cancer before age 45
- first or second degree relative with any cancer before age 45 or a sarcoma at any age
clinical manifestations of Von Hippel-Lindau (VHL) disease
- hemangioblastoma (CNS, retina)
- clear cell renal cell carcinoma
- bilateral kidney cysts
- pheochromocytoma
- pancreatic cysts and pancreatic neuroendocrine tumors
- endolymphatic sac tumor
- cystadenomas of genitourinary tract
(BE HPPCC)
VHL is a _________ gene located on chromosome ___
tumor-suppressor, 3p25-26
VHL targets ______ for ubiquination and degradation
HIF
phospholipid
glycerol-3-phosphate backbone with two fatty acyl chains (saturated or mono- or poly-unsaturated) at one end and polar head group at other
sphingolipid
- long acyl unit (sphingosine) with either of two polar head groups and an attached fatty acid chain
- NH instead of one of the C’s
cholesterol
hydroxylated ring at one end and fatty acid chain on other
Uptake and synthesis of cholesterol are regulated by ________
SREBP
With low cholesterol, the transcription factor is released from SREBP via ______________________
RIP (regulated intramembrane proteolysis)
Proteases that cleave SREBP release ___________
basic helix-loop-helix
_______ binds SREBP and sterols like cholesterol
SCAP
_______ binds SCAP when cholesterol is high
Insig
plasma volume
3 liters
ECF volume
13 liters + 5 for “third space”
ICF volume
27 liters
physical forces that can determine the gating properties of ion channels
- electric field (voltage-gated, membrane potential)
- mechanical (stretch)
- chemical (synaptic receptors)
- temperature
mechanisms cells evolved to keep from swelling and bursting
- make cell membrane impermeable to water
- build wall around cell which resists osmotic pressure
- balance water concentrations osmotically
molarity
number of moles of solute/L of solution
-measure of concentration
osmolarity
total concentration of solute molecules (sum of molarity)
equivalents
number of “combining weights” of an ion per liter
-convert mosM for each ion, multiply most by valence of each ion
tonicity
effect of a solution on a cell
_____ protein regulates dissociation of SNARE protein
NSF
arterial blood pH
7.34-7.44
venous blood pH
7.28-7.42
concentration of HCO3- in blood
24mmHg
PCO2 in blood
40mmHg
One clinical exam finding that suggests irritable bowel disease is _________
erythema nodosum
major metabolic disturbances in DKA
- hyperglycemia (elevated blood sugar)
- acidosis
- potassium derangement
- dehydration
action of insulin in liver
- stores glucose (as glycogen) and lipid
- stops lipid and glycogen breakdown
action of insulin in muscle
- stores glucose
- makes protein
action of insulin in adipose
-stores glucose and triglyceride
loss of RB gene can occur via…
- local events
- somatic recombination
- chromosome loss
- loss and duplication
In FAP, the mutation is a change from ________ to __________
glutamic acid to glutamine
BRCA1 is important in regulating _____________
quality control for DNA damage
Most mutations in p53 are _________ mutations
missense
Li-Fraumini syndrome is inherited in an ________ fashion
autosomal dominant
common ways cancer-associated “hits” can occur
- point mutation (activating oncogene or suppressing tumor inactivation)
- amplification
- deletion
- epigenetic silencing via methylation
- insertion of retrovirus containing an oncogene
T/F: In Li-Fraumini syndrome, “hits” can be on different genes
true
VHL comes from a ________ mutation in ______ of the VHL gene
missense, exon 3
VHL is an ___________ inherited cancer syndrome
autosomal dominant
VHL is a ___________ gene
tumor-suppressor
Where are CNS hemangioblastomas found in patients with VHL?
cerebellum, brainstem base, cervical spine (not forebrain)
actions of VHL protein
- regulates HIF (hypoxia inducible transcription factor)
- suppresses aneuploidy
- microtubule stabilization/primary cilia maintenance
Gag encodes for ________
internal virion proteins
Env encodes for ______________
membrane glycoproteins
Pol encodes for ______________
reverse polymerase
V-myc mimics ________________
c-myc proto-oncogene (cell growth/division)
_____________ are the most common cause of death in patients with Von Hippel Lindeau
renal cell carcinomas
Describe the position of activation and inactivation gates in action potentials
- rest: activation closed, inactivation open
- rising: both open
- falling: activation open, inactivation closed
- hyperpolarization: both closed
causes of hyperkalemia (2)
- K+ escaping from cells
- kidney that can’t keep [K+]o below 5mM
systemic therapies for metastatic renal cell carcinoma include…
- vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitors
- MTOR inhibitors
- immunotherapies
Gating of ion channels is controlled by… (3)
- temperature (hot/cold)
- mechanical deformation
- membrane potential
- extracellular chemicals (taste, olfaction, neurotransmitters)
- intracellular second messengers (ATM, cAMP, Ca2+)
major functions of the ER
- synthesis of lipids
- control of cholesterol homeostasis
- synthesis of proteins on membrane bound ribosomes
- co-translational folding of proteins and early post-translational modifications
- quality control