Review Slides Part 3 Flashcards
Elevated IFP can cause _________ drug uptake.
decreased
Some chemodrugs require ________ for maximal efficiency so hypoxia can cause resistance.
oxygen
Low pHe causes ___________ across the plasma membrane which prevents drug delivery for many chemotherapeutic agents.
pH gradient
Well-oxygenated cells require _________ of the dose of anoxic cells to achieve a given level of cell killing.
1/3
The oxygen enhancement ratio is given by:
OER = (radiation dose in hypoxia) / (radiation dose in air) for the same level of biological effect.
The OER for x-rays in most cells is _________. At <3.0 Gy dose, OER is _________. For high LET OER is __________.
2.5 - 3
reduced
1 -1.5
The diffusion distance of oxygen in respiring tissue is ____________.
100-180 um
Cells beyond diffusion distance become _________, but cells bordering on these regions are _________ although ________.
necrotic
viable
hypoxic
Acute and chronic hypoxia can _________ in the same tumor.
coexist
Oxic-hypoxic cycles in tumors have been observed to occur with periodicities of ____________.
minutes
If reoxygenation occurs between fractions, then the radiation killing of initially hypoxic cells will be _________ and the hypoxic cells have _________ impact on response.
greater
less
5 ways to improve tumor oxygenation are:
1. ___________
2. ___________
3. ___________
4. ___________
5. ___________
increasing oxygen-carrying capacity in the blood
anti-vascular endothelial growth factor (VEGF) therapies
decreasing tumor oxygen consumption
mild hyperthermia
inhibitors to block Ras signaling
Radiosensitizing properties of oxygen are due to its ____________ so other ___________ might act as sensitizers.
electron affinity
electron-affinic compounds
____________ compounds contain members that sensitize hypoxic cells both in vitro and in animal tumors.
nitromidazoles
Hypoxic cytotoxins reduce the influence of hypoxia on radiation response using __________ that are toxic under hypoxic conditions.
bioreductive
The bioreductive drug ____________ is cytotoxic to hypoxic cells at oxygen concentrations up to ________ uM/L or pO2 _______ mmHg.
tirapazamine (TPZ)
10
6
Tirapazamine can combine with chemotherapeutic agent ________ to increase its toxicity. Shown efficacy in lung and H&N cancers.
cisplatin
The four Rs of radiobiology are ________, __________, _________, and ________.
repair
repopulation
redistribution
reoxygenation
In Repair of sublethal damage, DSB is repaired by enzymes in ________.
hours
In Repopulation, cell growth takes _______.
~ week
In Redistribution (Reassortment) of cells the cell cycle effect takes ________.
~ day
In Reoxygenation the oxygen effect takes _________.
hours to days
Dividing dose in number of fractions _________ normal tissues by allowing for _______ and __________ of normal tissue.
spares
repair
repopulation
Dividing the dose in number of fractions _________ to tumor through __________ and __________ into radiosensitive phases.
increases damage
reoxygenation
redistribution
________ is the regrowth of tumor cells, in humans the delay is ________.
proliferation
4 weeks
The extra dose to counter proliferation is only accounted for in _____________ tissues.
early responding
The alpha/beta ratio for early responding tissues is ________ and for late responding tissues is ________.
10 Gy
2-3 Gy
_______ responding tissues are more sensitive to change in fractionation.
late
The dominant factor in determining late effects is ___________.
fraction size
The major problems with chemotherapy are _________ such as gut, kidney and bone marrow, and ___________.
toxicity to normal tissues
intrinsic and developed drug resistance
___________ is a drug that binds to EGFR, inhibiting cell growth, inducting apoptosis and decreasing matrix metalloproteinase and VEGF.
Cetuximab
__________ is a chemotherapy drug that induces normalization of vessels in tumor and makes them more response to cytotoxic chemo and RT.
Bevacizumab
Photodynamic therapy uses ___________ and __________.
photosensitizing agent
particular type of light
When photosensitizers in PDT are exposed to a specific wavelength of light, they produce a form of __________ that ______ nearby cells.
oxygen
kills
