Hall+Recall

Front 1

are x-rays and gamma rays directly or indirectly ionizing? Directly or indirectly acting?

Back 1

indirectly ionizing and indirectly acting (2/3rd)

Front 2

are neutrons directly or indirectly ionizing? Directly or indirectly acting?

Back 2

indirectly ionizing but directly acting

Front 3

What is the lifetime (in seconds) of OH radical and subsequent DNA radical

Back 3

10^-9 seconds and 10^-5 seconds

Front 4

what is the speed of light in (m/s) and its relationship with wavelength and frequency

Back 4

c (3x10^8 m/s) = wavelength (lambda) x frequency (v)

Front 5

order the following in terms of increasing energy? Wavelength? And frequency? (microwave, visible light, UV, x-rays, infrared, and radiowaves)

Back 5

RMIVUX (increasing energy)
XUVIMR (increasing wavelength)
RMIVUX (increasing frequency)

Front 6

relationship btw energy and plank's constant

Back 6

energy = planks constant (h) x frequency

Front 7

relationship btw wavelength in (angstroms) and energy (in keV)? How much is 1 angstrom in meters?

Back 7

lambda (angstroms) = 12.4/energy (keV)
1 angstrom = 10^-10 m

Front 8

in photoelectric interactions what is the energy of the ejected orbital electron

Back 8

Kinetic energy = hv (energy of incident photon) - binding energy of electron (Eb)

Front 9

directly or indirectly ionizing: alpha particles, electrons, gamma rays, neutrons, x-rays

Back 9

directly - charged particles (alpha, electron, protons)
indirect - uncharged (x and gamma, neutrons)

Front 10

how is compton process related to atomic number

Back 10

it is INDEPENDENT OF ATOMIC NUMBER

Front 11

what type of aberration occurs in prereplication (G1): chromosome or chromotid?

Back 11

chromosome

Front 12

what type of aberration occurs in postreplication (late S or G2): chromosome or chromotid?

Back 12

chromotid

Front 13

anaphase bridge is what type of aberration: chromosome or chromotid?

Back 13

chromotid

Front 14

incidence of radiation-induced aberrations is a what type of function of dose

Back 14

linear-quadratic

Front 15

what lowest dose can be detected with peripheral lymphocytes

Back 15

0.25 Gy

Front 16

DNA is positive or negative charged?

Back 16

negative

Front 17

what is D0? Estimated for mammals? Estimated # of base damage, SSB, and DSB per cell?

Back 17

dose that induces 1 lethal event per cell (average) resulting in 37% cell survival
mammals = 1-2 Gy
Base > 1000, SSB 1000, and DSB 40

Front 18

dicentrics and rings are what type of chromosome aberration

Back 18

chromosome

Front 19

what happens to cell once telomere finished

Back 19

senescence

Front 20

if I was running a gel electrophoresis what pH would I want the solution to be in if I wanted to study single strand breaks

Back 20

alkaline

Front 21

order these in terms of increasing ion pairs, energy and damage: blob, track and spur

Back 21

spur -> blob -> short track

Front 22

telomerase is what type of enzyme

Back 22

reverse transcriptase

Front 23

how do u calculate survival fraction

Back 23

SF = (# of colonies counted)/(# of cells seeded x plating efficiency)

plating efficiency = # of colonies counted/ number of cells seeded in optimal conditions

Front 24

linear quadratic equation of survival fraction

Back 24

SF = e^(- alpha*D - beta*D^2)

Front 25

what does the alpha/beta ratio signify in one sentence

Back 25

the dose at which the linear and quadratic components of cell killing are equal

Front 26

which is linear quadratic: mitotic or apoptotic death

Back 26

mitotic

Front 27

which has a dose-rate effect: mitotic or apoptotic death

Back 27

mitotic

Front 28

what is the equation of D10 with relation to D0

Back 28

D10 = D0 * 2.3

Front 29

what does "n" (the extrapolation number) represent? How does it change with the shoulder?

Back 29

represents the number of targets in a cell to be damaged to lose clonogenicity
increase shoulder (narrow) - small n (neutrons)
increase n - broad shoulder (x -rays)

Front 30

what are the units of alpha/beta

Back 30

gray

Front 31

how are n, Dq and D0 related

Back 31

log n = Dq/D0

Front 32

how is D0 and SF related

Back 32

SF = e^(-D/D0)

Front 33

do cells with significant SLDR capacity have a low or high alpha/beta

Back 33

low

Front 34

D0 is what relation to e (logarithmic)

Back 34

D0 = e^ (- 1)

since Probability = e ^(-n) ; with n representing # of clonogenic tumor cells

Front 35

Fowler estimated that 1 log increas in cell kill increased the cure rate by how much

Back 35

15%

Front 36

1 cm3 (1 gram) of tumor cells contains how many cells

Back 36

10^9

Front 37

what part of the cell cycle accounts for cell cycle times between species

Back 37

G1

Front 38

order the following in terms of most radiosensitive to resistant - last S, early S, G2, M, G1?

Back 38

G2/M < G1 < early S < late S

Front 39

how does OER vary across cell cycle phases

Back 39

lower for cells in G1 than in S

Front 40

describe relationship btw dna damage, atm, p53, and p21 and cdks

Back 40

dna damage -> ATM -> p53 -> p21/waf1 which inhibits cdks which then prevent phosphorylation and keeping rb hypophosphorylated ( activation rb and e2f)

Front 41

does p53 have a role in G2-> M check point

Back 41

yes

Front 42

what cyclins are synthesized in G1

Back 42

D and E

Front 43

what cyclins are synthesized in S

Back 43

A

Front 44

what cyclins are synthesized in G2

Back 44

A and B

Front 45

what cyclins are synthesized in M

Back 45

B

Front 46

what does E2F do (clue: something with Rb)

Back 46

phosphorylate Rb (which actually places it in inactive - so cell can move through G1)

Front 47

cdk 4 is in what check point

Back 47

G1-> S

Front 48

what happens when Rb is unphosphorylated? What phosphorylates Rb?

Back 48

bound to E2F and cyclin A in G1 which inhibits progression. Cyclin D and cdk 4 complex phosphorylates Rb keeping it inactive

Front 49

is p16 pro or inhibitory of the cell cycle

Back 49

inhibitory; it inhibits cdk4 with then doesn't allow phosphorylation of Rb (which keeps it active)

Front 50

cdk1 is in what check point

Back 50

G2->M

Front 51

in cells with very long G1's whats more radioresistant early G1 or late G1?

Back 51

early G1 > late G1

Front 52

what are 2 possible explanations for the variation in sensitivity of the cell cycle?

Back 52

change in the amount and shape of DNA
varying levels of sulfhydryl compounds (radioprotectors)

Front 53

what form of repair is done at the G1 phase of the cell cycle

Back 53

non-homologous recombination

Front 54

what form of repair results in immune deficiency if defective: HRR or NHEJ

Back 54

NHEJ

Front 55

what is the name of the disease that has decreased ATR gene expression

Back 55

Seckel's disease

Front 56

are patients with ataxia telangiectasia sensitive to ionizing radiation

Back 56

YES; autosomal recessive; increased risk of lymphomas;

Front 57

artemis is used in which type of repair HRR or NHEJ and if it is defective results in what immune condition

Back 57

NHEJ; SCID

Front 58

which of the following are radiosensitive: SCID, NIJMEGEN BREAKAGE SYNDROME, FANCONI ANEMIA, ATAXIA TELANGIECTASIA, AND XERODERMA PIG

Back 58

all except fanconis (sometimes) and xeropigmentosum (never)

Front 59

what is the component of radiation damage that can be modified by manipulation of the postirradiation conditions called

Back 59

potentially lethal damage

Front 60

does PLDR occur with neutron irradiation

Back 60

non-homologous recombination

Front 61

what explains the increase in survival if dose rate is reduced

Back 61

repair of sublethal damage

Front 62

what is the benefit of iridium

Back 62

small size and low photon energy (shielding)

Front 63

what sites has radiolabeld immunoglobulin used

Back 63

hepatoma and hosgkin's lymphoma

Front 64

incorrect base (example adenosine with incorrect base) is repaired with what type of repair? What happens when defective (radiosensitivity)?

Back 64

base excision; increase in mutation rate but not cellular radiosensitivity;

Front 65

what type of repair fixes bulky adducts such as pyrimidine dimers? What happens with defective?

Back 65

nucleotide excision repair; no change in radiosensitivity but change in UV sensitivity and alkalating agents; example disease xeroderma pigmentosum

Front 66

what are the key players in NHEJ?

Back 66

Ku80, DNA-PKc, Artemis? XRCC4

Front 67

what is VDJ recombination (what type of repair does it show up) and why is it important

Back 67

NHEJ; recombination important in developing antibodies; reason for SCID development

Front 68

what are the key players in HRR?

Back 68

ATM/ATR, BRCA 1/2, NBS, MRE11, Rad50/51/52, MMS, MU581

Front 69

what represents a transitional role btw HRR and NHEJ

Back 69

single strand annealing

Front 70

sublethal damage repair is actually repairing what

Back 70

double strand breaks

Front 71

describe how a tissue's capacity for SLDR corresponds to the cell survival curve

Back 71

increased SLDR means increased Beta which means low alpha/beta, which means broad shoulder

Front 72

what dose rate range is SLDR most pronounced

Back 72

1-100 cGy/min

Front 73

describe the reason for the inverse dose rate effect

Back 73

a lowering of the dose allows cells that were arrested in G1 to proceed but then get caught at G2 (which is a more the more sensitive cycle)

Front 74

effective half life equation

Back 74

effective half life used in radionuclides; takes into account half life of radioisotope and biologic half life ; 1/te = 1/tp + 1/tb

Front 75

continous irradiation would be more effective for long cell cycle cells or short cell cycle

Back 75

long cell cycle (reassortment)

Front 76

what is the disadvantage of HDR

Back 76

less sparing of late normal tissues

Front 77

the variation of total dose in comparing different dose rates is larger for late or early tissues

Back 77

late

Front 78

what are the disadvantages of I131 when compared to yttrium90

Back 78

lower tumor and higher total body dose/toxicity since it also emits gamma rays (whereas yttrium only emits beta-ray)

Front 79

define OER in words

Back 79

ratio of doses administered under hypoxic to aerated conditions needed to achieve the same biological effect (hypoxic/aerated) (usually in the ange of 2-4

Front 80

how does the OER for neutrons compare to x-rays

Back 80

it is lower for higher LET radiation (1.6)

Front 81

how does OER vary across cell cycle phases

Back 81

it is lower for more radiosensitive phases (lower OER for G1 than S)

Front 82

what is the level of oxygen in percent and mm Hg required for sensitivity halfway btw hypoxia and full oxygenation? What percent do u see flattening?

Back 82

0.5% or 3 mm Hg; 3% results in flattening (same level as 100% full oxic cells)

Front 83

what are the two types of hypoxia and their etiologies?

Back 83

chronic - limited diffusion range of oxygen through respiring tissue
actue - temporary closing of tumor blood vessels

Front 84

what are eppendorf probes used for

Back 84

to measure oxygen

Front 85

describe the "slow" and "fast" component of reoxygenation

Back 85

slow - reoxygenates chronically hypoxic cells as tumor shrinks
fast - reoxygenation from open/close blood vessel

Front 86

what is the diffusion distance approx for oxygen through tissue

Back 86

70 micrometers

Front 87

what type of agent is used in noninvasive imaging of hypoxic areas?

Back 87

2-nitroimdiazole

Front 88

what two tumor sites have demonstrated the link of hypoxia and tumor progression

Back 88

cervix and sarcoma

Front 89

describe the interaction of HIF-1 in response to O2 and anoxic areas (mention hydroxylation and an important downstream target)

Back 89

in prescence of oxygen, HIF1 alpha is hydroxylated which causes it to bind VHL (vonhippaulindau protein) this causes ubiquitin degradation of HIF1 alpha

in response to hypoxia -> HIF1alpha is not hydroxylated and binds to its beta subunit and then upregulates genes involved in angiogenesis, erythropoiesis, and tissue remodeling

Front 90

what is the interaction of OER and dose rate (increased dose? Decrease dose rate)

Back 90

OER increase with increasing dose
OER decrease with decreasing dose rate

Front 91

what is the average hypoxic fraction

Back 91

15%

Front 92

describe method for determining the radiation resistant fraction of tumor

Back 92

asphyxiation of animal to create 100% hypoxic tumor; survival curve generated for both 100% hypoxic and room air; using difference in surviving fraction btw aerated conditions determines the resitance fraction

Front 93

how are apoptosis and hypoxia related

Back 93

in response to hypoxia -> p53 is upregulated which induces apoptosis;

Front 94

which of the following are pro-angiogenic: angiopoietin, angiostatin, TNF alpha, prostaglandins, TGF beta, interferon alpha, beta, thrombospondin, endostatin?

Back 94

angiopoietin, prostaglanding, TGFbeta, TNF alpha, VEGF

antiangiogenic: angiostatin, endostatin, trhombospondin

Front 95

define RBE in words

Back 95

dose of 250 kv xrays divided by dose of test radiation to produce the same effect

Front 96

how does RBE change with increasing LET

Back 96

it increases to a max at 100 kev/micromet then decreases

Front 97

how does RBE change with increasing capacity for SLDR

Back 97

increases ; in other words with survival curves with large shoulder, u see higher RBEs

Front 98

how does OER change with increasing LET

Back 98

decreases

Front 99

150 MeV protons have an LET of what? 10 MeV ?

Back 99

0.5 for high energy; 4.7 for lower energy

Front 100

as dose is increased what happens to RBE

Back 100

it decreases

Front 101

as number of fractions increase what happens to RBE (also can be interpreted as decreasing dose rate)

Back 101

RBE increases

Front 102

as you increase energy of incident photon/particle, what happens to LET

Back 102

it decreases

Front 103

as you increase LET what happens to the shoulder

Back 103

smaller and steeper

Front 104

cerebrovascular syndrome results from what TBI dose and what onset

Back 104

100 Gy, death in 24-48 hrs

Front 105

gastrointestinal syndrome results from a TBI dose of what and in what timeframe

Back 105

10 Gy; death in 5-10 days

Front 106

hematopoietic syndrome results from TBI of what dose and what timeframe

Back 106

2.5-5 Gy; death in 30-60 days

Front 107

what is the LD50 for humans without medical intervention? With medical intervention?

Back 107

3-4 Gy; with 6-7 Gy

Front 108

what is the dose window over which bone-marrow transplants may be useful

Back 108

8-10 Gy

Front 109

what is the dose-reduction factor used to evaluate and what is the equation

Back 109

used to evaluate radioprotectors: dose in presence of drug divided by the dose in absence of drug

Front 110

describe the mechanism and pharmokinectics of amifostine

Back 110

free radical scavenger; acts as prodrug - dephosphorylated by alkaline phosphatase to active form

Front 111

what is the dose limiting toxicity of amifostine?

Back 111

hypotension

Front 112

what type of effect has a threshold dose, and whose severity increases with dose

Back 112

deterministic (ex - cataracts)

Front 113

what type of effect has a increasing probability with dose, no threshold, and dose not exhibit a dose-severity response

Back 113

stochastic (ex - cancer)

Front 114

what type of cancer was seen in radium dial painters? Ankylosing spondylitis? Children irradiated for benign cancers, thymus, or H&N? Fluoroscopies in TB patients in nova scotia?

Back 114

bone cancers in dial painters
leukemia in anklosing spondylitis
thyroid cancer in children
breast cancer in Tb patients

Front 115

due radiation induced malignancies tend to appear early, at same time, or later than spontaneous malignancies

Back 115

same time

Front 116

2 types of risk moels for radiation carcinogenesis: absolute and relative. Which one does BEIR use

Back 116

relative risk

Front 117

what is the excess cancer mortality per SV for LDR for the working population

Back 117

4 x 10^-2 / Sv (5 for whole)

Front 118

what is the excess cancer mortality per SV for HDR for the working population

Back 118

8 x 10^-2 / Sv (10 for whole)

Front 119

the dose response relationship for radiation-induced cancer is what relationship at low dosease and what shape at higher doses

Back 119

linear at low, lin-quad at moderate doses

Front 120

what type of leukemia's are seen with radiation induced

Back 120

AML and CML (NOT CLL)

Front 121

what is the genetic mutation doubling rate dose

Back 121

1 Sv (1 Gy)

Front 122

what response model is preferred for solid cancer? For leukemia?

Back 122

solid - linear; leukemia - linear quadratic

Front 123

permanent sterility dose in men? Single vs fractionated dose? Females?

Back 123

6 gy single; 3 gy fractionated

females: 12 gy prepubertal to 2 Gy premenopausal

Front 124

azoospermia and oligospermia doses

Back 124

0.5 Gy and 0.15 Gy

Front 125

what is the doublind dose required to double the spontaneous mutation incidence

Back 125

1 Gy

Front 126

ICRP estimate for hereditary risk of radiation is… (general) and working

Back 126

0.2% per SV (0.1 % / SV for workin)

Front 127

what is a robertsonian translocation

Back 127

fusion of two chrmosomes

Front 128

in humans, describe the lengths of preimplantation, organogenesis, and the fetal period

Back 128

0-9 days: preimplantation
10 days - 6 weeks: organogenesis
6 - term: fetal period

Front 129

which is permanent growth retardation: irradiation in the organogenesis phase or fetal period

Back 129

fetal period

Front 130

what results in neonatal death - preimplanation or organogenesis

Back 130

organogenesis (death at the time of birth)

Front 131

describe the timing of mental retardation and microcephaly: 0-7 weeks, 8-15 weeks, 16-25 weeks

Back 131

microcephaly 0-7
both 8-15 (mental retardation most pronounced during this period)
mental retardation 16+

Front 132

what is the excess absolute risk per gray of childhood cancer in fetus irradiation? What is the lowest dose that can cause an increase (and suggest therapeutic abortion)

Back 132

6%, 0.1 Gy (10 cgy)

Front 133

once pregnancy declared what is the maximum permissable dose to the fetus per month (NCRP)

Back 133

0.5 mSv

Front 134

with increasing dose what happens with the latency period to develop cataracts

Back 134

decreases

Front 135

how do dead cells get removed in the lens

Back 135

they don't (unique feature)

Front 136

minimum dose to produce cataract in single dose? Fractionated?

Back 136

2 Gy; 10 Gy (fractionated)

Front 137

what would suggest a cataract that is likely caused by radiation

Back 137

originates from the posterior pole

Front 138

what type of effect is cataracts: deterministic or stochastic? What happens with increasing dose?

Back 138

deterministic; severity increases w/ dose (past threshold)

Front 139

what are the 3 types of background radiation

Back 139

cosmic rays, terrestial radiation, radionuclides present in background

Front 140

where is cosmic radiation higher at the equator or at the poles

Back 140

poles

Front 141

what % of lung cancers are caused by radon?

Back 141

10%

Front 142

rank the following in terms of effective dose to the brain: CT, x ray, nuclear imaging, cerebral angiography

Back 142

x ray, CT, nuclear, angiography

Front 143

what parameter of CT's must be adjusted for kids

Back 143

kV and mAs (smaller size)

Front 144

erythema of the skin occurs at what dose and what etiology

Back 144

permeable capillaries, 2 Gy

Front 145

the loss of IQ in utero irradiation (points/sv)

Back 145

30 points per SV

Front 146

what is the typical dose (in mCi) for PET

Back 146

10 mCi

Front 147

what is genetically significant dose (GSD)

Back 147

equivalent dose to gonads weighted for age, gender, & probability of having kids

dose to the gonads x # of children each member expected to have divided by # of people in the population

Front 148

give Gray in rad and in erg

Back 148

1 Gy = 100 rad (radiation absorbed dose)
1 rad = 100 erg/g

Front 149

radiation weighting factor (Wr) is representative of ? What is the value for photons, electrons, protons, alpha particles, neutrons

Back 149

RBE; photons, electrons 1; protons 2; alpha particles 20; neutrons up to 20

Front 150

equivalent dose is in what unit (what is the old unit)

Back 150

absorbed dose x weighting factor = Sievert (100 rem (rad equivalent man))

Front 151

effective dose takes into account what?

Back 151

takes into account tissue weighting factor (Wt); to account for unevenly distributed absorption of dose.

Front 152

(BM, breast, colon, lung, stomach), (bladder, esophagus, gonads, liver, thyroid), (bone surface, brain, kidneys, salivary glands, skin) - order these groups in decreasing tissue weighting factor

Back 152

(BM, breast, colon, lung, stomach .12) > (bladder, esophagus, gonads, liver, thyroid .05) > (bone surface, brain, kidneys, salivary glands, skin .01)

Front 153

what is committed equivalent/effective dose used for

Back 153

intergral over 50 years of equivalent/effective dose after intake of radionuclide

Front 154

what is collective equivalent/effective dose used for; Units?

Back 154

takes into account group or population; man-sievert or person-sievert

Front 155

what is the % increase per seivert for severe mental retardation

Back 155

40%/Sv (at 8-15 weeks)

after 15 weeks - 10%

Front 156

what is the carcinogenesis per Sv for the general population (low doserate)

Back 156

5%/Sv

Front 157

what is the hereditary effects per Sv fo rhte general population

Back 157

0.2%/Sv

Front 158

no occupational exposure should be permitted before what age

Back 158

18

Front 159

under the NCRP what is the worker's lifetime effective dose per year and in lifetime

Back 159

50 mSv per year; age x 10 mSv lifetime

Front 160

what is the dose limit per year for the lens of the eye and the skin for workers? For gen public?

Back 160

150 mSv and 500 mSv; 50 mSv

Front 161

in special situations where you have to allow persons less than age 18 to work what is the annual effective dose limit

Back 161

1 mSv

Front 162

annual effective dose limit for members of the public (frequent) exposure? Infrequent?

Back 162

1 mSv and 5 mSv

Front 163

what is the remidial action level of radon by the EPA

Back 163

148 Bq/m^3

Front 164

what is the neglible individual dose considered

Back 164

.01 mSv (1 mrem)

Front 165

what is the average annual equivalent dose to monitored radiation workers

Back 165

2 mSv

Front 166

how does the ICRP annual dose limit differ from the NCRP? Which allows for more dose at a younger age?

Back 166

the ICRP has a limit of 20 mSv per year over 5 years
the NCRP has a 10 mSv x age lifetimes
both have 50 mSv annuale limit

Front 167

how does the ICRP pregnancy dose limit differ from the NCRP

Back 167

ICRP: 2 mSv to the surface of the woman's abd;
NCRP: monthly limit of 0.5 mSv

Front 168

enzymes that cleave DNA after recognizing a specific sequence. Those moste useful for constructing recombinant molecules leave a "sticky" end - a single-strand overhang of two-four nucleotides that can pair with a complementary strand

Back 168

restriction endonucleases

Front 169

autonomously replicating DNA molecule into which foreign DNA fragments are inserted and then propagated in a host cell. Vectors include plasmids, bacteriophage, bacterial artificial chromosomes, and viruses

Back 169

vector

Front 170

PCR adaptation to analyze RNA expression; amplify RNA w/ reverse transcriptase than add primers and separate on gel electrophoresis

Back 170

reverse transcription PCR

Front 171

very sensitive PCR technique that enables high-throughput nucleic acid analysis and quantification; amplification nad measurement take place in same vessel using fluorescent oligo specific for gene of interest

Back 171

quantitative real-time PCR

Front 172

putting a functional version of a defetive gene into cells to correct the phenotype associated with the defect by hybridization to oligonucleotide probes, microarrays, or sequencing

Back 172

functional complementation

Front 173

strategy used to clone a gene for which no information is available about its protein product. (ex tumor suppressor); incorporates family inheritance

Back 173

positional cloning

Front 174

identifies regions of chromosomal duplication or deletion. The genes in the abnormal region can then be analyzed by expression or functional studies to identify candidate genes in the region

tumor DNA harvested and digested w/ restriction enzyme - labeled with red fluorescent and green done to control; hybidize to DNA microarray --> observe increase (amplify) or decrease red (deletion)

Back 174

comparative genomic hybridization

Front 175

useful platform for studying gene expression changes (RNA), gene aneuploidy (CGH), and DNA-protein interactions (ChIP-chips). The primary advantage is the sheer number of sequences that can be analyzed at one time

Back 175

microarray

Front 176

structural variations in DNA caused by point mutations, deletions, or insertions can result in restriction fragments of different lengths, which can often be detected by Southern blotting. Can be used as genetic markers to map genes to specific chromosomal locations and identify aberrant genes causing disease

Back 176

restriction fragment length polymorphisms

Front 177

used to study promoter function in intact cells, either to identify transcription factor interactions with promoters or to dissect mechanisms of regulation. DNA purified by it can be analyzed individually by PCR or by hybridization to promoter microarrays

Back 177

chromatin immunoprecipitation (ChIP)

Front 178

subcloning by recombination, functinonal complementation, hybridization, oligonucleotide probe, positional cloning: are all types of ?

Back 178

ways to screen a DNA library

Front 179

what can be used to isolate gene if no info available about gene's protein product ? Linkage analysis can facilitate location, then can used "linked DNA" sequence; useful for tumor suppressor genes

Back 179

positional cloning

Front 180

used to reduce expression of gene; double strand RNA vectors induce antiviral response and interact w/ RNA-inducing silencing complex --> silecnes the gene (affects gene translation)

Back 180

si-RNA; RNA interference

Front 181

used to identify the specific sequence bound by a transciption factor;

short DNA radiolabeled -> incubated with cellular extracts and electrophoresed -> if transcription factor binds, DNA sequence moves slower

Back 181

electrophoretic mobility shift assay (EMSA)

Front 182

"inverse Northern blot"; cellular RNA is reverse transcribed, amplified w/ modified nucleotide that allows fluorescence detection -> hybridized to array of sequences

Back 182

spotted arrays

oligo arrays

Front 183

what does far western blotting do

Back 183

protein-protein interaction

Front 184

2D PAGe is used to study what

Back 184

posttranslational modification of proteins - proteins separated by charge and size

Front 185

order the following vectors in terms of increasing DNA capacity for transfection: cosmids, yeast artificial chromosomes, viruses, plasmids, bacteriophage lambda

Back 185

plasmid, bacteriophage, cosmid, yeast artificial chromosomes, viruses

Front 186

which polarity does dna move towards: positive or negative

Back 186

positive

Front 187

radioactive probe is mixed with cell extract containing the DNA binding proteins (transcription factors) and run on polyacrylamide gel

retardation of the probe indicates binding of protein with this DNA segment

Back 187

gel shift assay

Front 188

gene arrays, cDNA libraries, qPCR all begin with a ____ type of transcript

Back 188

RNA

Front 189

reporter gene assays, gel mobility shift assay, and chromatin immunoprecipitation have all been used to evaluate ?

Back 189

promoter genes

Front 190

The protein of interest is isolated with a specific antibody. Interaction partners which stick to this protein are subsequently identified by Western blotting.[1] Interactions detected by this approach are considered to be real. However, this method can only verify interactions between suspected interaction partners. Thus, it is not a screening approach. A note of caution also is that immunoprecipitation experiments reveal direct and indirect interactions. Thus, positive results may indicate that two proteins interact directly or may interact via one or more bridging molecules. This could include bridging proteins, nucleic acids (DNA or RNA), or other molecules.

Back 190

Co-immunoprecipitation is considered to be the gold standard assay for protein–protein interactions, especially when it is performed with endogenous (not overexpressed and not tagged) proteins.

Front 191

The premise behind the test is the activation of downstream reporter gene(s) by the binding of a transcription factor onto an upstream activating sequence (UAS). For the test, the transcription factor is split into two separate fragments, called the binding domain (BD) and activating domain (AD). The BD is the domain responsible for binding to the UAS and the AD is the domain responsible for the activation of transcription.[1][2] The Y2H is thus a protein-fragment complementation assay. only when both hybridize together do u see an outcome.

Back 191

two-hybrid screen

Front 192

technology typically used to validate protein interactions. It is based on the association of fluorescent protein fragments that are attached to components of the same macromolecular complex. Proteins that are postulated to interact are fused to unfolded complementary fragments of a fluorescent reporter protein and expressed in live cells. Interaction of these proteins will bring the fluorescent fragments within proximity, allowing the reporter protein to reform in its native three-dimensional structure and emit its fluorescent signal

Back 192

Bimolecular fluorescence complementation (also known as BiFC)

Front 193

ras, neu, myc, EGFR, and bcr-abl are all examples of what?

Back 193

oncogenes

Front 194

NF1,2, ECAD, PTCH, PTEN, APC are all examples of ?

Back 194

tumor suppressors

Front 195

WT1

Back 195

wilms - tumor suppressor

Front 196

PTEN

Back 196

cowden syndrome - hamartoma - tumor suppressor

Front 197

MEN1

Back 197

pituitary, pancreas, parathyroid - tumor suppressor

Front 198

Rb is active phosphorylated or hypophosphorylated? When is it bound to E2F)

Back 198

active when hypophosphorylated and bound to E2F

Front 199

TGFbeta has what relationship with Rb

Back 199

it keeps Rb active by inhibiting Rb phosphorylation (which keeps Rb in its "active" hypophosphorylated state); does this through the promotion of P21 and P15 INK (which are inhibitors of Rb)

Front 200

which caspase is the initiator in the extrinsic pathway? Intrinsic?

Back 200

caspase 8; 9

Front 201

which caspases are considered effectors

Back 201

3,6,7

Front 202

mdm2 has what effect on p53

Back 202

it inhibits

Front 203

does BID inhibit or promote apoptosis

Back 203

promote

Front 204

describe the relationship btw VHL and HIF

Back 204

VHL normally inhibits HIF; HIF in response to hypoxia is upregulated causing angiogenesis

Front 205

TSP-1 - pro or anti angiogenic

Back 205

antiangiogenic; no p53 -> decreased TSP1

Front 206

does radiation increase or decrease ceramide

Back 206

increase (ceramide increases apoptosis)

Front 207

p21 has what function - downregulates or upregulates cell cycle

Back 207

downregulates cell cycle (cdk4 and 6)

Front 208

how does cdk4 and 6 promote the cell cycle

Back 208

by phosphorylating Rb thereby inactivating it which lets it release E2F which goes to upregulate cyclinE

Front 209

which cyclins are in G1?

Back 209

D and E

Front 210

which cylins are in S and G2?

Back 210

A

Front 211

which cyclins are in G2 and M?

Back 211

B

Front 212

chk1 has what affect on the cell cycle

Back 212

it is inhibitory; chk1 promotes phosphorylation of Cdc25A which inhibits cyclin E and A

Front 213

when is Ras active - with GTP or GDP

Back 213

GTP; inactivated by GAP (GTPase activiating protein)

Front 214

what does p16 do

Back 214

competes with cyclin D for binding to CDK4, thus inhibiting activity of CDK4 (which normally promotes cell cycle)

Front 215

Cockayne's syndrome is defective in what repair process

Back 215

NER, increased sensitivity to UV radiation

Front 216

are people with ataxia telangiectasia sensitive to UV radiation

Back 216

no

Front 217

ATM mutation lacks checkpoint in G1/S or G2/M

Back 217

BOTH

Front 218

is MAPK lead to growth or growth arrest

Back 218

arrest (via p53, fos, jun, myc)

Front 219

shape of dose and incidence of tumor control and normal tissue damage

Back 219

sigmoidal

Front 220

ratio of tumor response to normal-tissue damage is called

Back 220

the therapeutic index

Front 221

after irradiation most cells die a _______ death

Back 221

mitotic (also apoptotic but lesser)

Front 222

describe spleen colony assay

Back 222

recipient animals (irradiated prior to experiment to sterilize spleen) inoculated with bone marrow from mice that received test dose of radiation. Number of spleen nodules counted

Front 223

where are thyroid and mammary cells implanted in cell survival assay

Back 223

mouse fat pads

Front 224

how is tolerance of cord related to length irradiated

Back 224

for short lengths (< 1 cm), tolerance dose varies markedly with cord length irradiated; for > few centimeters, virtually independent of cord length

Front 225

is looking at rodent skin, breathing rate following lung irradiation, myelopathy: functional end points or cell survival endpoints

Back 225

functional endpoint

Front 226

which way on a dose response curve does the curves move if you add a radiosensitizer

Back 226

to the left

Front 227

what is the typical orientation of the dose response curves, which is on the left : tumor control or normal tissue damage

Back 227

tumor control

Front 228

does overall time versus dose/fx important in spinal cord irradiation

Back 228

overall time not important

Front 229

generalized symptoms (those unrelated to cell killing), such as fatigue, nausea, vomiting may be mediated by…

Back 229

radiation-induced inflamm cytokines

Front 230

what requires more does to destroy: differentiated cell or dividing cell

Back 230

differentiated cell

Front 231

time interval btw irradiation and expression in tissue damage depends on…

Back 231

life span of mature functional cells and the time it takes for a cell born in the stem compartment to mature

Front 232

tolerance doses more sensitive to changes in dose per fraction for early or late effects

Back 232

late

Front 233

which one: serial or parallel organized? Little or no functional reserve, and risk of developing complication less dependent on volume irradiated ….. Risk of complication influenced by high-dose regions and hot spots

Back 233

serial (spinal cord, etc.)

Front 234

early radiation response in skin -- epidermis or dermis? Late response?

Back 234

epidermis --early. Dermis--late

Front 235

most sensitve late responding tissue

Back 235

lung

Front 236

FSUs in kidney organization

Back 236

parallal

Front 237

whats affected first white or gray matter in brain following RT

Back 237

white;

Front 238

is spinal cord affected by length of irradiation

Back 238

for very small lengths yes; for lengths greater than few CM tolerance independent of length irradiated

Front 239

permanent sterility dose in males (fractionated)

Back 239

2.5-3 Gy (fractionated); sterility - 6 Gy

Front 240

is womens libido affected by irradiation to ovaries

Back 240

yes (in men libido preserved)

Front 241

rank in terms of radiosensitivits (most to least): kidney, lung, brain, liver and heart; what is the common theme of these organs?

Back 241

lung, kidney, liver, heart, CNS

all late responding tissues

Front 242

most common radiation induced injury to lung

Back 242

acute pericarditis

Front 243

what does SOMA stand for

Back 243

Subjective, Objective, Management, Analytic

Front 244

what casarett's classification: differentiating intermitotis cells, which divide regularly but in which there is some differentiation between divisions, and which are variably differentiated?

Back 244

II

I: stem cells of classic self-renewal tissues, which divide regularly

III: reverting postmitotic cells, which do not divide regularly but can divide under the appropriate stimulus
IV: fixed postmitotic cells which are highly differentiated and appear to have lost the ability to divide

Front 245

what are the 2 classic early responding tissues

Back 245

GI epithelium and skin

Front 246

is the spinal cord structurally defined or undefined

Back 246

undefined (similar to skin, mucosa) meaning clonogenic cells can migrate from 1 FSU to another and allow repop

versus defined - kidney liver and lung

Front 247

what are the two broad categories (types) that Michalowki described in radiation pathology

Back 247

H-type - or heirarchical cells: stem -> mature partially diff cells -> functional cells
F-type - or flexible cells : rarely divide under nl circumstances but can be triggered

tissues are hybrids of above

Front 248

interleukin's role with regards to radiation

Back 248

radioprotector (increase shoulder and Do of survival curve)

Front 249

TGF-beta's role with radiation

Back 249

strong inflamm response; can inhibit interleukin 1 and TNF; linked to fibrosis and vascular changes in late effects

can increase radiation damage

Front 250

TNF role in radiation

Back 250

mediates inflamm response -> prolif of fibroblasts, inflamm cells, and endothelial cells

protects hemotopoietic cells and sensitizes tumor cells to radiation

correlates with RT complications; cachexia

Front 251

what type of assay: transplated tumor on flank or back is measured daily , grown to specific size and then some are given treatment others are control. Advantage?

Endpoint is TCD50 (? What is this)

Back 251

growth delay (single dose) or tumor cure (graded doses)
adv: avoids artifacts involved in disaggregating the tumor

TCD dose at which 50% of the tumors are controlled

Front 252

what type of assay: mice with advanced leukemia irradiated /controls and liver harvested then made into single cell suspension and injected into peritoneal cavity -> number of mice that develop leukemias scored. Relevant is # of cells required to transmit tumor to 50% of mice

Back 252

Dilution assay technique

Front 253

what type of assay: tumors irradiated in situ -> irradiated/controls -> made into single cell sups -> ijected -> number of lung colonies counted

Back 253

lung colony assay

Front 254

what type of assay: tumor treated in vivo (alive) -> tumor removed and prepared into single cell sups -> plated on petri dish -> counted

Back 254

in vivo/in vitro assay

Front 255

what type of assay: transplating from 1 species to another and using congenitaly immune deficient mice to accept human tumors

Back 255

xenograft

Front 256

mitotic index is fraction of cells in mitoses; what is the equation?

Back 256

MI = λ Tm / Tc; where lambda is a correction factor to allow for fact that the cells are not distriubted evenly in the cell cycle b/c the # of cells doubles during mitosis

Front 257

what is the labeling index? Equation

Back 257

fraction of cells that are in S (marked by those that take up titriated thymidine); LI = λ Ts / Tc; where lambda is a correction factor to allow for fact that the cells are not distriubted evenly in the cell cycle b/c the # of cells doubles during mitosis

Front 258

describe the percent labeled mitoses technique? What does it aim to estimate?

Back 258

uses thymidine/bromodeoxyuridine that stain in S phase and chart their time at regular intervals to count percent in mitoses. All the phases of the cell cycle can be approximated with this technique. Ts can be approx by following time of cells to enter mitoses and completely leave (begining or vice versa end); in practice estimated by middle width

Front 259

describe the bromodeoxyuridine-DNA assay in flow cytrometry? What is it used for?

Back 259

cells stained simultaneously with two dyes that fluoresce at different wavelengths: one binds in proportion to DNA content to indicate the phase of the cell cycle, and the other binds in proportion to bromodeoxyuridine incorporation to show if cells are synthesizing DNA

can be used for Tpot and to estimate labeling index and Ts

Front 260

an approximate estimate of cell cycle time with regards to S phase is what?

Back 260

3 times S-phase time

Front 261

what is the equation for cell loss factor? What does a value of 100% represent?

Back 261

ф = 1 - Tpot/Td
ratio of rate of cell lost to rate of new cell production; 100% correlates to steady state (ie no growth no regression); estimated to be greater than 50% for all tumors (median 77)

Front 262

what is the relationship btw Tpot (potential doubling time), labeling index, and S phase cell cycle time

Back 262

Tpot = l Ts/Labeling Index

Front 263

what does increased cell loss do to cell doubling time (Td)? Decreased growth fraction?

Back 263

both increase Td (actual cell cycle doubling time)

Front 264

as tumor size increases what happens to growth fraction? Rate of cell loss? Tumor growth rate?

Back 264

growth fraction decreases; rate of cell loss increases; tumor growth rate decreases

Front 265

proliferating cells / (proliferating + quiescent cells) = ?

Back 265

growth fraction (LI/MI)

Front 266

high or low growth fraction assoc with radiosensitivity

Back 266

high

Front 267

if I inject titriated thymidine into an animal with a tumor then harvest the tumor and calculate the fraction of cells labeled (LI) and divide by the fraction of mitoses (MI) what would I get

Back 267

growth fraction

Front 268

four R's of radiobiology

Back 268

Repair of sublethal damage
Reassortment of cells w/in cell cycle
Repopulation
Reoxygenation

Front 269

Strandquist plot/iso effect curve? Do late tissues have a flat or steep curve?

Back 269

relation btw total dose and overall treatment time; "time" includes # of fx; slope of line for skin is around 0.33

late tissues have steep curve reflecting increased repair capacity

Front 270

prolonging overall time within normal RT affects what type of reactions

Back 270

early

Front 271

What type of tissues (early or late) are more sensitive to changes in fractionation pattern

Back 271

late-responding tissues (because of large shoulder)

Front 272

triggering of surviving cells to divide more rapidly as a tumor shrinks after irradiation or txt w/ cytotoxic agent

Back 272

accelerated repopulation

Front 273

when does accelerated repopulation start in H&N cancers

Back 273

around 4 weeks; about 0.6 Gy needed per day to compensate

Front 274

basic aim of hyperfractionation

Back 274

separate early and late effects (decrease late effects)

Front 275

basic aim of acceleration

Back 275

to reduce repopulation

Front 276

randomized trial has shown what for hyperfractionation

Back 276

increased LC and increased survival; no increase in acute or late effects

Front 277

EORTC trial of accelerated txt results? In terms of LC? Survival? Late effects? Early effects?

Back 277

increase in LC; no increase in survival
unexpected increase in late effects (consequential effects from severe early effects and incomplete repair secondary to short time interval btw fxs)

Front 278

CHART results? In terms of TC? Acute and late effects?

Back 278

same tumor control, worse acute effects, and decreased late effects (because of low dose)

Front 279

logic of ARCON (accelerated hyperfractionation radiation therapy while breathing carbogen and with the addition of nicotinamide)

Back 279

acceleration to overcome cell prolif, hyperfractionation to spare late responding tissues, carbogen to overcome chronic hypoxia, and nicotinamide to overcome acute hypoxia

Front 280

decrease in local control per day in increasing overall txt time for H&N cancers? Cervix

Back 280

1.4%

0.5%

rapid prolif not seen in breast or prostate

Front 281

BED

Back 281

"biologically effective dose" = nd(1+ d/ (alpha/beta)

Front 282

what are eppendorf probes used for

Back 282

measuring oxygen tension in tumors

Front 283

if survival fraction following a 2 gy dose was higher for a certain tumor cell line versus another tumor cell line; would you expect its response to treatment to be better or worse? Courtnay assay?

Back 283

worse; shown in head and neck with regards to local control and cervix

courtenay assay - cells grown as spheres or clumps in semisolid agar gel

Front 284

what is a commonly used parameter to model proliferative potential but has not panned out in studies?

Back 284

Tpot (potential doubling time); if high, tumor has high proliferative potential

Front 285

what is meant by SF2? Where has it been shown to be useful

Back 285

SF2 refers to the fraction of cells surviving a dose of 2 Gy; used in identifying tumors that are radiosensitive and resistant (> or < then 0.4)

Front 286

neutrons are (directly or indirectly) ionizing

Back 286

indirectly

Front 287

how do the biologic properties of neutrons differ from x-rays in terms of OER, sublethal damage repair, and cell cycle sensitivity variation

Back 287

reduced OER, little or no SLDR, and less variation in cell cycle

Front 288

what sites have neutrons been clinically proven

Back 288

salivary gland, prostate cancer, and soft-tissue sarcoma

Front 289

describe concept of boron neutron capture therapy

Back 289

deliver a drug containing boron and then deliver low-energy thermal neutrons that interact with the boron to produce alpha-particles

Front 290

why is boron a good choice for neutron capture therapy

Back 290

large cross setion, emits short range alpha particles, and can be incorporated in wide range of compounds

Front 291

comparison of RBE, OER btw protons and x-rays

Back 291

similar

Front 292

carbons in comparison to xrays and protons: RBE

Back 292

increased LC and increased survival; no increase in acute or late effects

Front 293

unique way carbon ion dose can be visualized

Back 293

PET - carbon strips other carbons neutrons and results in 11C and 10C which are positron emitting isotopes

Front 294

halogenated pyrimidines mechanism of action

Back 294

incorporated into DNA by competing with thymidine; must be incorporated into DNA for sensitization to occur. Cells must be grown in presences of analogue for several cell cycles….extent of radiosensitization increases with amount incorporated

Front 295

toxicity of bromodeoxyuridine

Back 295

phototoxicity --> rash

Front 296

toxicity of misonidazole

Back 296

peripheral neuropathy

Front 297

which radiosensitizing hypoxi cell has the least toxicity and was shown to have a benefit for head and neck CA in LC and OS

Back 297

nimorazole

Front 298

what class/action is tirapazamine

Back 298

organic nitrooxide -- cytotoxic against hypoxic cells; found use as adjunct to chemo agents

Front 299

nitroimidazoles labeled with radionuclide can be used as markers for…

Back 299

hypoxic cells

Front 300

how do hypoxic-cell radiosensitizers work?

Back 300

mimics oxygen by "fixing" damage produced by free radicals

Front 301

which of the following are bioreductive: misonidazole or mitomycin C

Back 301

mitomycin C;

Front 302

tirapazamin is what class of drug? Side effects?

Back 302

hypoxic cytotoxic drug; nausea and severe mm cramping

Front 303

please describe the four aspects of ARCON trial (acceleration, carbogen, hyperfractionation, and nicotinomide)

Back 303

carbogen -> chronic hypoxia
nicotinomide -> actue hypoxia
acceleration -> prolif
hyperfractionation -> spare late tissue

Front 304

what are 3 ways of radiosensitizing cells

Back 304

hyperbaric oxygen
improve O2 supply to tumors (perfluorocarbons, transfusions)
hypoxic cell radiosensitizers

Front 305

downside to retrovirus

Back 305

only infect dividing cells

Front 306

downside to adenoviruses

Back 306

invoke immune response (but infect both dividing and nondividing cells)

Front 307

what is suicide gene therapy? examples of suicide gene therapy?

Back 307

transduce cell with gene that converts a prodrug into a cytotoxic agent

cytosine deaminase which converts to 5FU. HSV-tk plus ganciclovir

Front 308

what is cytotoxic virus

Back 308

kill cells with mutated gene (most work on p53)

preferentially targets cancer cells with a cytotoxic virus and spares normal cells
- uses an adenovirus that replicated only in p53 mutant cells, killing them thru cell lysis
- early trials show significant growth suppression in animal models and human H&N ca; however, only produce PR

Front 309

what is molecular immunology (ie cancer vaccines)

Back 309

seeks to provoke a cellular immune response against the cancer by injecting a vaccine genetically engineered to express immune stimulatory molecules or tumor-specific antigents

Front 310

what is tumor-suppressor gene therapy

Back 310

replacement, with a correct copy, of the mutated gene that initiates or contributes to the malignant phenotype

Front 311

what is linking a radiation-inducible promotor to a cytotoxic agent; the cytotoxic agent is "turned on" only in the carefully delineated radiation field

Back 311

radiation-activated genes or radiogenetic therapy

Front 312

why are traditional anticancer drugs toxic to intestinal epithelium and hematopoietic stem cells?

Back 312

because they have a high growth fraction

Front 313

MOA of alkylating agents

Back 313

ability to substitute alkyl groups for hydrogen atoms in DNA, include nitrogen mustard derivatives, cyclophosphamide, chlorambucil, melphalan, and the nitrosoureas (BCNU and CCNU)

Front 314

MOA of antibiotics

Back 314

bind to DNA and inhibit DNA and RNA synthesis, include dactinomycin, doxorubicin, daunorubicin, and bleomycin

Front 315

MOA of antimetabolites

Back 315

analogues of the normal metabolites required for function and replication; include MTX, 5FU, cytarabine, and 5-azacytidine

Front 316

dose-response relationship of chemo (in comparison to RT)

Back 316

similar, initial shoulder

Front 317

oxygen effect of chemo?

Back 317

varies on drug - some target aerated cells, some hypoxic cells

Front 318

development of resistance to one drug results in cross-resistance to other drugs with a different mechanism of action

Back 318

pleiotropic resistance

Front 319

are alkylating agents as a class considered cell cycle specific

Back 319

cell-cycle NONspecific

Front 320

what are the 3 classes of bioreductive agents? Do they favor hypoxic or oxic conditions?

Back 320

fused-ring benzoquinones (mitomycin C), organic N-oxides (tirapazamine), dual-function nitroheterocyclic (RB6145)
favors hypoxic situations

Front 321

what is the mdr gene do? (hint - chemo)

Back 321

mdr - multidrug resistance gene; membrane bound protein that pumps drugs out of the tumor cells; reversed by calcium channel blocking drugs

Front 322

contrast vinca alkaloids and taxanes

Back 322

vinca inhibit spindle formation; taxolsinhibit disassembly

Front 323

Busulfan

Back 323

DNA alylation; myelosuppression; CML and polycythemia vera (and pre BMT)

Front 324

carboplatin

Back 324

intra and interstrand crosslinks; myelosuppression (esp thrombocytopenia); multiple cancers

Front 325

carmustine

Back 325

alkylating agent cellcycle independent - PENETRATES BLOODBRAIN BARRIER; myelosuppression (esp thrombo); brain, mult myeloma

Front 326

chlorambucil

Back 326

alkylating agent cell cycle indepen; meylosuppression; CLL - other leukemias/lymphomas (lowgrade)

Front 327

cyclophosphamide

Back 327

alkylating agent cell-cycle indepen; myelosuppression, hemorrhagic cystitis; multiple sites

Front 328

dacarbazine

Back 328

alkylating agent methylates guanine bases; myelosuppression - SYNERGY W/ RT; malignant melanoma and hodgkin's

Front 329

ifosfamide

Back 329

alkylating agent non-cell cycle dependent; meylosuppression, hem cystitis, CNS tox; recurrent germ cell tumors

Front 330

lomustine (CCNU)

Back 330

alkylating agent - cell cycle indep PENETRATES BLOOD BRAIN BARRIER; myelosupp (esp thrombo); brain and hodgkin's

Front 331

mechlorethamine

Back 331

alkylating agent - cell cycle indepen; powerful vesicant, secondary leukemia; hematologic malignancies - hodgkin's and topically for t-cell lymphoma

Front 332

melphalan

Back 332

alkylating agent - cell cycle indepen; myelosuppression, secondary leukemia; multiple myeloma

Front 333

oxaliplatin

Back 333

alkylating agent - disrupts DNA via intra and interstrand cross links; neurotoxicity; metastatic colorectal

Front 334

procarbazine

Back 334

alkylating agent - cell cycle indepen PENETRATES BLOOD BRAIN BARRIER; myelosupp; hodgkin's

Front 335

temozolomide

Back 335

alkylating agent - PENETRATES BLOOD BRAIN BARRIER; myelosupp; brain tumors

Front 336

cisplatin

Back 336

produces intra and interstrand cross links; nephrotoxicity and ototoxicity; INTERM SYNERGY W/ RT; multiple

Front 337

bleomycin

Back 337

antibiotics cause DNA strand breaks directyl via creation of hydroxyl radicals; pulmonary toxicity; STRONG SYNERGY W/ RT; germ cell tumors, hodgkin's, SCC

Front 338

dactinomycin

Back 338

antibiotics inhibts transcription by complexing w/ DNA; moderate vesicant STRONG SYNERGY WITH RT; wilm's, ewings, rhabdo, many others

Front 339

doxorubicin

Back 339

antibiotic intercalating agent; potent vesicant, cardiomyopathy STRONG SYNERGY W/ RT (sever skin reactions); breast and others

Front 340

mitomycin C

Back 340

antibiotics inhibits DNA and RNA synthesis; vesicant and myelosuppression STRONG SYNERGY W/ RT; anal

Front 341

5FU

Back 341

antimetabolites inhibitor of thymidylate synthase; gi toxicities, dermatitis, and hand-foot syndrome SYNERGY W/ RT; multiple

Front 342

capcitibine

Back 342

oral 5FU; myelosuppressin hand foot sydrome INT SYNERGY WITH RT; metastatic breast and colorectal

Front 343

cytarabine

Back 343

incorporated into DNA during replication --> strand termination PENETRATES BLOOD-BRAIN BARRIER; myelosupp; AML and ALL

Front 344

fludarabine

Back 344

antimetabolite; neutrotoxicity; CLL

Front 345

gemcitibine

Back 345

antimetabolite; inhibits ribonucleotide reductase ; STRONG SYNERGY WITH RT myelosupp; pancreatic, bladder

Front 346

hydroxyurea

Back 346

inhibitor of ribonucleotide reductase --> inhibition of DNA synthesis

Front 347

methotrexate

Back 347

antimetabolite interferes w/ dihydrofolate reductace; encephalopathy with intrathecal, should be admin prior to cranial irradiation; multiple malignancies; toxicity - peripheral neuropathy

Front 348

l-asparaginase

Back 348

cleaves the amino acid asparagine which is essential for proliferation; hypersensitivity; ALL

Front 349

trastuzumab

Back 349

monoclonal antibody against her2/neu growth factor; cardiotoxicity; breast

Front 350

megestrol acetate

Back 350

steroidal progestational agent; hormonal changes; breast and endometrial ca; appetite stimulation

Front 351

cetuximab

Back 351

blocks egfr receptor dimerization; acne STRONG SYNERGY W/ RT; colorectal and head and neck ca

Front 352

imatinib mesylate

Back 352

specific tyrosine kinace inhibitor which inhibits bcr-abl, ckit; myelosuppression; CML and metastatic GIST

Front 353

rituximab

Back 353

directed against CD20; fever, chills; lymphoma

Front 354

docetaxel

Back 354

inhibits mitotic spindle apparatus by stabilizing tubulin polymers; myelosuppression; multiple malignacies

Front 355

paclitaxel

Back 355

inhibits depolymerization of tubulin in spindle apparatus -> apoptosis; weak synergy with RT - myelosupp, neuromyopathy; multiple malignancies

Front 356

etoposide VP16

Back 356

topoisomerase II inhibitor; myelosuppression; germ cell tumors and SCLC

Front 357

irinotecan

Back 357

topoisomerase I inhibitor; myelosuppression; metastatic colon

Front 358

vinblastine

Back 358

inhibitor of tubulin polymerization; soft tissue vesicant; multiple malignancies Hodgkins

Front 359

vincristine

Back 359

inhibitor of tubulin polymerization; vesicant, neurotoxict; nonhodgkins

Front 360

vinorelbine (navelbine)

Back 360

inhibitor of tubulin polymerization; mild vesicant, myelosuppression; metastatic breast and NSCLC

Front 361

goserelin acetate (zolodex)

Back 361

agonist, inhibits pituitary-gonadal axis function causing steroid hormone withdrawal from prostate and breast cancer cells; endocrine; prostate and met breast

Front 362

leuprolide acetate (leupron)

Back 362

agonist, inhibits pituitary-gonadal axis function causing steroid hormone withdrawal from prostate and breast cancer cells; endocrine; prostate and met breast

Front 363

bicalutamide (casodex)

Back 363

nonsteroidal antiandrogens; endocrine + constipation; prostate

Front 364

tamoxifen

Back 364

nonsteroidal antiandrogens;

Front 365

anastrozole

Back 365

nonsteroidal aromatase inhibitors; breast

Front 366

amifostine

Back 366

free radical scavavenger; hypotension, n/v, and somnolence; radiation protectant

Front 367

describe heat survival curves (y and x axis; contrast from x-rays)

Back 367

y axis - survival; x axis - time at Temperature (T); similar to radiation

Front 368

what is the significance of the break point (43 C) with regards to sensitivity

Back 368

below this temp, change in T results in more sensitivity than above this temp

seen on a arrhenius plot for heat inactivation; inverse of D0 (y-axis) and T (x-axis)

Front 369

is there a difference in sensitivity to heat between normal and malignant cells?

Back 369

no

Front 370

what phase of cell cycle is most sensitive to hyperthermia

Back 370

S phase (specificially late S)

Front 371

hyperthermia and pH and nutrition

Back 371

cells with low pH and nutritionally deprevied (ie tumors) MORE sensitive to heat

Front 372

does hypoxia protect cells from hyperthermia

Back 372

NO

Front 373

what damages cells more rapidly - hyperthermia or xrays? Why

Back 373

heat damages tissues more rapidly than x-rays because heat kills differentiated as well as dividing cells and cells die in interphase (contrast from next or subsequent mitosis in xrays)

Front 374

what is thermotolerance

Back 374

induced resistance to a second heat exposure by prior heating; complication during fractionated hyperthermia

Front 375

what does heat do to vasculature for tumor and normal tissues?

Back 375

heat preferentially damages tumor vasculature; after heating, blood flow goes down in tumors but increases in normal tissues

Front 376

what is the most successful noninvasive technique to measure hyperthermia

Back 376

MRI

Front 377

thermal dose is expressed in terms of ?

Back 377

CEM43°C - cumulative equivalent minutes at 43 C exceeded by 90% of monitored points w/in tumor

Front 378

how does hyperthermia work synergistically with radiation (specifically why does it radiosensitive)

Back 378

hyperthermia inhibits repair

Front 379

what is the mechanism of damage for hyperthermia

Back 379

damage to plasma membrane and inactivation of proteins (denaturation)

Front 380

what is thermal enhancement ratio

Back 380

radiation dose without heat/radiation dose with heat (increases with increasing temperature) (generally > 1.0)

Front 381

how does hyperthermia and chemo interact

Back 381

heat makes chemo more effective

Front 382

benefits and contrasts of microwaves and ultrasound in hyperthermia

Back 382

microwaves - good localization at shallow depths; poor at greater depths; ultrasound - deep heating can be achieved but bone and air cavities get in the way

Front 383

what types of cells does hyperthermia affect - dividing or differentiated cells?

Back 383

both

Front 384

what type of death do heated cells die by - mitotic or apoptotic

Back 384

apoptotic

Front 385

what is thermal dose equivalent

Back 385

minutes the tissue has to be held at 43 degrees C to suffer same biological damage as produced by the actual temperature; for lower dosease factor of 1/4th ; for greater factor of 2 (per degree difference)

other words; for every degree above 43 - time is halved and for below 43 time is multiplied by 4-5

Front 386

What is a dirty bomb

Back 386

bomb with radioactive materials that when explodes results in spread of that material (cs 137)

Front 387

what is a hidden RED

Back 387

hidden radiation exposure device - simply droping a gamma emitting source into a busy location so people are exposed

Front 388

what is the goal of decontamination in event of radiologic terroris (w/ regards to backgroun radiation)

Back 388

count less than twice background

Front 389

what % of patients present with second cancer

Back 389

10%

Front 390

what tolerates retreatment better: early or late responding tissue

Back 390

early-responding tissues

Front 391

pair production is related to energy, Z how?

Back 391

independent of energy (but must be greater than 1.02 Mev) and proportional to Z^2

Front 392

what changes in coherent scattering

Back 392

only the direction of the incident photon (no energy transfer, no ejected electrons)

Front 393

what is specific ionization and its relation to particle velocity

Back 393

ion pairs per unit length (decreases with increasing particle velocity)

Front 394

LET can be calculated what two ways? Are they similar for xrays? Neutrons?

Back 394

track average or energy average; same for x rays but different for neutrons; energy avg better for biological effects

Front 395

what is the rough LET for neutrons? For high energy protons? For 250kv xrays?

Back 395

100, 0.5, 2

Front 396

how is LET related to mass? Charge? Velocity/energy?

Back 396

increases with mass and square of charge; decreases with increasing velocity and energy

Front 397

DNA strand breaks are to the bases or sugars

Back 397

sugars

Front 398

what does UV light cause in DNA

Back 398

pyrimidine dimers - type of bulkly DNA lesion

Front 399

what is H2Ax and its significance? How do u interpret if its phosphorylated?

Back 399

H2Ax is a histone that is phosphorylated by ATM in response to DNA damage; can be used a sensitve measure for DNA double strand break

Front 400

terminal deletions and sister unions are what type of aberration

Back 400

chromotid

Front 401

ATM plays a major role in which cell cycle check point

Back 401

G2/M

Front 402

size of proton

Back 402

1.6 x 10 ^ -15

Front 403

how far can hydroxyl radical diffuse

Back 403

double the distance of double helix ( 4 nm )

Front 404

spurs and blobs are most associated with what kind of damage

Back 404

locally mulstiply damaged sites

Front 405

spur vs blob in terms of energy; type of radiation that causes them

Back 405

“spur” –
contains up to 100 eV of energy (e- transfers an average of 60 eV to water & cellular molecules per event)
contains ~ 3 ions pairs (ie. 33 eV produces 1 ion pair)
diameter ~ 4 nm (diameter of DNA = 2 nm)
for x-rays and -rays, 95% of the energy deposition events are spurs

“blob” – contains 100-500 eV of energy
contains ~ 12 ion pairs
diameter ~ 7 nm
damage produced is much more difficult to repair
common for neutrons and -particles (ie. damage produced is qualitatively different than x-rays)

Front 406

what is adaptive response

Back 406

cells irradiated with a lose dose may be more resistant to a subsequent higher dose

Front 407

how do u solve for an equivalent doses when comparing multifraction vs single dose using Dq?

Back 407

acute dose - Dq = each fraction - Dq
in 2 fx example: acute dose = fx x 2 - Dq

Front 408

as a general rule how much larger is D0 in hypoxic conditions

Back 408

3 x D0 for hypoxic conditions compared to aerobic

Front 409

when n (extrapolation number) is equal to 1 what does this signy with regards to the survival curve

Back 409

Beta = 0 or there is no shoulder

Front 410

what is flexure dose?

Back 410

0.1 x alpha/beta ratio ; defined as the point when curve bends signifincatly; to fully exploit sparing, doses per fraction should be as low as this

Front 411

what is tissue rescue unit

Back 411

Minimum number of FSU's to maintain tissue fx

Front 412

what is the cell loss factor for most tumors

Back 412

> 50%

Front 413

is PTEN a tumor suppressor or oncogene

Back 413

tumor suppressor (assoc with cowden syndrome - hamartomas)

Front 414

total cell cycle time is approximately how much longer than S-phase cycle time

Back 414

3 x Ts

Front 415

are cells killed when exposed to hydroxyurea

Back 415

s phase cells killed and block introduced

Front 416

what are the layers of a spheroid

Back 416

asynchronous/aerobic in outer layer, noncycling G1-like in middle, central zone of G1-like hypoxic cells

Front 417

dilution assay, lung colony system and in vivo/in vitro techniques are all examples of ….

Back 417

clonogenic assays

Front 418

bloom syndrome is a result of what deficiency

Back 418

ligase deficiency

Front 419

what is on the axes of an isoeffect curve? What do late responding tissues look like (steep or flat)?

Back 419

effective single does plotted as function of overall txt time; late responding tissues have steeper slope (reflects increased repair capacity)

Front 420

which of the 4 Rs spares normal tissues and which of them kills tumor

Back 420

repair and repopulation spares normal tissues, while reassortment and reoxygenation kills tumor

Front 421

Know the OERs of X-rays, alpha particles and neutrons

Back 421

X-rays 2.5, Neutrons 1.6, Alpha 1.0

Front 422

these are all used for what: 2-Nitroimidazole Markers (pimonidazole and EF5), Endogenous Markers (Carbonic Anhydrase 9, HIF), Comet Assay (requires rapid sampling of irradiated tumor), Noninvasive Imaging (PET, SPECT with various labeling agents, etc)

Back 422

to measure hypoxia

Front 423

how do u get the fraction of hypoxia cells via an experiment

Back 423

ratio of aerated SF / Hypoxic SF

Front 424

how long does S, G2, and M last in hours

Back 424

S is around 8 hours, G2 is around 4 hours, and M is around 1

Front 425

when does radiosensitivity is halfway and saturated in terms of Oxygen tension

Back 425

3 mm Hg or 0.5% O2 causes halfway
30 mm Hg or 3 % O2 saturation

Front 426

What will distinguish the tumors cells lining the vessels from those farther away? (with regards to labeling index)

Back 426

higher labeling index

Front 427

Does LET increase with increasing energy?

Back 427

No, it decreases, as less energy is deposited in tissue.

Front 428

What are the units of LET?

Back 428

KeV / um

Front 429

what happens to RBE with increasing alpha/beta ratio (no shoulder)

Back 429

decreased RBE

Front 430

at what LET does OER go to 1

Back 430

160 KeV/um

Front 431

what is the LET for protons (150 Mev)? 250 kvp photons? 14 MeV Neutrons? 2.5 MeV alpha particles?

Back 431

Protons - 0.5
250 kvp photons - 4.7
neutrons - 12 (track); 100 (energy)
alpha - 166

Front 432

do neutrons have a bragg peak?

Back 432

no

Front 433

who is more radioresistant - a human or a mouse?

Back 433

mouse

Front 434

They asked what was the major organ limiting toxicity of TBI?

Back 434

Bone marrow suppression

Front 435

What is the most likely effect seen after 1.5 Gy of total body irradiation?

Back 435

lymphopenia/neutropenia

Front 436

What is the defination of DRF Dose reduction factor?

Back 436

Ratio of dose in presence of drug/dose in absence of drug to produce a given level of lethality

Front 437

what are thiols and how do they work?

Back 437

radioprotectors; They work by free radical scavenging by the SH- group AND by donating hydrogen atom to facilitate direct chemical repair at sites of DNA damage

Front 438

If the drug had a dose enhancement ratio of 1.1 and patient can tolerate 45 Gy without drug, what dose can now be given?
• 40.5 Gy
• 49.5 Gy.

Back 438

40.5 Gy

Front 439

Had to know the exact definition of dose reduction factor:,

Back 439

for radioprotectors
• radiation dose in the presence of drug, divided by radiation dose in the absence of drug.

Front 440

how do nitro-imadazole drugs work? Sensitize or protect?

Back 440

sensitizers; taken up by hypoxic cells and substitute for oxygen to fix radiation damage

Front 441

difference in latency period btw solid tumors and leukemia

Back 441

leukemia has shortest latency - peak by 10 years versus solid tumors with longer latency on order of 10-50 years

Front 442

after chernobyl accident there was an increased risk of what type of malignancy

Back 442

thyroid cancer

Front 443

What tumors are seen after tx of cervix cancer?

Back 443

Bladder most common, followed by rectal and vaginal.

Front 444

Type of cancers seen:
Early radiologists ______ cancer
Thorotrast ______ cancer
Radium dial painter _____ cancer
Uranium miner ______ cancer
Tinea capitis tx ______ cancer

Back 444

Early radiologists Skin cancer
Thorotrast Liver cancer
Radium dial painter Bone cancer
Uranium miner Lung cancer
Tinea capitis tx Thyroid cancer

Front 445

what is the ratio of solid tumor to leukemia

Back 445

5 to 1

Front 446

how many ergs/gram is equal to 1 rad

Back 446

100 erg/g

Front 447

what are the major organs at risk for carcinogenesis (ie highest tissue weighting factor)

Back 447

bone marrow, breast, colon, stomach

Front 448

what is the units of integral dose

Back 448

joules (given by Gray x kg of tissue)

Front 449

describe the difference in interaction with neutron for low (< 6 MeV) and high energy

Back 449

at lower energies - dominant process is elastic scattering (interaction with hydrogen atoms) - recoil protons
at higher energies - inelastic scattering - spalliation products

Front 450

what form is ATM active (monomer or dimer)

Back 450

monomer (inactive dimer autophosphorylates)

Front 451

D0 = D37 in what scenario

Back 451

when n = 1

Front 452

what is the tunel assay (dUTP nick end labeling) used for

Back 452

to detect apoptosis (as well as DNA ladder, and Annexin V)

Front 453

conversion of sphingomyelein to ceramide occurs at what part of the cell

Back 453

cell membrane (involved with apoptosis (intrinsic pathway))

Front 454

How does RBE change with low dose rate, with hypoxia, with more fractionation, with low alpha/beta

Back 454

RBE increases (need more x-rays for same effect)

Front 455

male: sterility dose for single dose and fractionated? Temporary sterility?

Back 455

4-6 Gy (single dose) or 2 Gy fractionated

temporary: 15 cGy in 1 fx or 40 cGy fractionated (decreases 2 months later and recovers 6-1 year)

Front 456

women: sterility dose for single and fractionated

Back 456

3 Gy in 1 fx vs 20 Gy fractionated

prepuberity - higher 12 Gy

Front 457

absolute mutation rate for humans estimated at…

Back 457

0.2 % per SV

Front 458

brca2 can be mutated in what condition

Back 458

fanconi's anemia

Front 459

dose limiting toxicity of misonidazole (hypoxic cell radiosensitizers)

Back 459

peripheral neuropathy

Front 460

what is the RBE for neutrons for cataract formation

Back 460

20-50

Front 461

whats the radiation dose flying transcontinetal

Back 461

5 mrem

Front 462

what are the sources of natural background radiation

Back 462

cosmic radiation
terrestrial
radionuclides

Front 463

diagnostic x-rays take up how much of 6 mSv/year total? Nuclear medicine? Radon? Natural back ground ( minus radon)

Back 463

3 mSv; nuclear medicine 0.14 mSv
radon 2 mSv + 1 mSv (natural background)

Front 464

types of cell loss include

Back 464

death from inadequate nutrition
apoptosis
death from immunologic attack
metastasis
exfoliation

Front 465

in hydroxyurea technique to produce synchronously dividing cell population where is the block and does it kill cells?

Back 465

block introduced at end of G1 and S-phase cells killed

Front 466

what does the nominal standard dose system used for? Can it be used for late effects?

Back 466

total dose for connective tissue related to number of fractions and overall txt time; only applicable to early tissues because based on skin data

Front 467

cells plated into 96 well then treated with radiation or chemo and allowed to grow; stained --> only taken by surviving cells;

cell growth quantitated by measuring density of stain in well by a spectrophotometer

can only be used for screening for activity

Back 467

colorimetric assay

Front 468

petri dish coated with mixture of fibronectin and fibrinopeptides

known # of tumor cells plated into 24 well plates then grown for 2 weeks and stained

cell growth quantified by measuring density of stain (DOES NOT MEASURE REPRODUCTIVE INTEGRITY)

Back 468

cell adhesive matris (CAM) assay

Front 469

which cells are affected in radiation pneumonitis

Back 469

type II pneumocytes

Front 470

what is the neglibible individual dose (annual) as defined by NCRP

Back 470

.01 mSV (1 mrem)

Front 471

How can you measure levels of a specific RNA sequence under various cellular conditions?

Back 471

northern blot (by intensity of the band)

Front 472

proteins made and released by host cells in response to the presence of pathogens such as viruses, bacteria, parasites or tumor cells. They allow for communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.

Back 472

interferons

Front 473

these allow for detection of changes in gene expression levels, genomic gains and losses, as well as detection of mutation in DNA (single nucleotide polymorphism)

Back 473

DNA microarrays

Front 474

this strategy relies upon the production of the gene product (protein) within the cell allowing for a detectable/measurable phenotype. Therefore, requires the whole coding region!

Example: screening for a
DNA repair gene that confers
Resistance to radiation or
chemical treatment.

Back 474

functional complementation

Front 475

This method allows for the identification of regulatory sequences within a promoter that can be bound by transcription factors. Also allows one to measure activation/reduction in transcription factor binding.

A DNA fragment from a genomic clone or a corresponding synthetic oligonucleotide, which is suspected of containing regulatory sequences, is end-labeled and then mixed with a protein extract/purified protein.
The binding of a protein to the DNA fragment reduces its mobility during gel electrophoresis.

Back 475

gel mobility shift assay

Front 476

2-D Gel electrophoresis is used to analyze dna, rna or protein

Back 476

protein

Front 477

1. Clone the region of DNA thought to act as a promoter
2. Sequence the region
3. Digest with appropriate restriction enzymes
4. Ligate to reporter gene so that the reporter can be transcribed in the cells of interest
5. Transform cells of interest with the various promoter:reporter constructs
6. Measure reporter-gene transcription rates by assaying the reporter gene product

Back 477

promoter bashing

Front 478

transgenic, knockout, scid, and nude mice. What exactly are they and what kinds of experiments they are useful for

Back 478

Nude mouse - xenograft models
Scid mice- defective non-homologous repair (defective DNA-PK), therefore can study repair defects. DNA-PK is also important in V(D)J recombination, which is why Scid mice have immunodeficiency.
Transgenic- expression of function
Knockout to see loss of function or gain of function

Front 479

What is the mechanism of action of gleevec

Back 479

Binds BCR-ABL receptors and induces apoptosis

Front 480

What is NF-kB?

Back 480

Transcription factor that is one of a number of anti-apoptotic agents. It inhibits caspase activation.

Front 481

describe radiation's role in ceramide production

Back 481

radiation --> ASMase activity increases which is responsible for conversion of sphingomyelin to ceramide

cells deficient in asmase can only generate ceramide from ceramide synthase which is negatively regulated by ATM

Front 482

APC - tumor supressor or oncogene

Back 482

supressor

Front 483

what's more sensitive arteries or veins

Back 483

arteries

Front 484

What is the role of basic fibroblast growth factor?

Back 484

induces endothelial growth; Protects against microvascular damage after RT; inhibits RT induced apoptosis

Front 485

does IL1 act as a radiosensitizer or protectant?

Back 485

increasing both shoulder and D0 of survival curve - protectant

Front 486

PDGF Beta decreases or increases damage as result of radiation

Back 486

increases damage to vascular tissue

Front 487

Lhermitte’s sign:

Back 487

demyelinating injury several months after treatment, persists for a few months to a year, but reversible, threshold 35 Gy, does not predict myelitis

Front 488

Which is not seen following liver irradiation? VOD, hepatitis, hepatomegaly, acities,

Back 488

VOD and Hepatitis are part of Radiation Induced Liver Disease. Ascites can be seen as a consequence of VOD. Hepatomegaly generally is not seen.

Front 489

does hyperbaric oxygen improve hypoxia?

Back 489

yes by increasing distance oxygen can diffuse

Front 490

mechanism of action for hypoxic cell sensitizers (nitroimidazoles)

Back 490

can penetrate/diffuse further than O2 to reach hypoxic areas
- differential effect is based on the premise that while tumors contain hypoxic cells, normal tissues do not
- nitroimidazoles act as both radiosensitizers and chemopotentiators for alkylating agents
- mechanism of action = substitution for oxygen in radiation-induced free radical reactions (“oxygen mimic”)
- only needs to be present in hypoxic regions of the tumor at the time of irradiation
- results in an increase in the slope of the hypoxic cell survival curve

Front 491

what is spatial cooperation

Back 491

radiation treats primary while chemotherapy treats metastases

Front 492

MOA: amsacrine

Back 492

topo II inhibitor

Front 493

MOA: bleomycin

Back 493

radiation-mimetic agent, more toxic to aerated cells since greater amount of damage

Front 494

MOA: dactinomycin

Back 494

inhibits RNA synthesis

Front 495

MOA: doxorubicin

Back 495

inhibits DNA synthesis and topo II

Front 496

MOA: etoposide

Back 496

topo II inhibitor

Front 497

MOA: MTX, 5 FU

Back 497

MTX - folic acid analog competes for DHFR

5FU - inhibits thmidylate synthetase

Front 498

MOA: topotecan, irinotecan, camptothecin

Back 498

topo I inhibitor

Front 499

generally are alkylating agents, antibiotics, and cisplatin cell-cycle specific or nonspecific

Back 499

nonspecific

Front 500

what type of chemo agen has a concave upward doseresponse curve

Back 500

antibiotics ( - mycin's)

Front 501

are taxanes and vinca alkaloids cell cycle specifice or nonspecific? Cytarabine and 5-azacytidine? Hydroxurea?

Back 501

all cell cycle specific

Front 502

what's defective in fanconi's anemia

Back 502

HRR BRCA2

Front 503

do u see less thermotolerance with low or high temp? Thermotolerance assoc with step up (progressive higher temps) or step down (start high and go to lower temp)?

Back 503

high

step up

Front 504

most common side-effect of TBI? Dose limiting toxicity?

Back 504

cataracts most common; pulmonary and kidney toxicity dose limiting

Front 505

what is the range of neutron and RBE for lower energy and high energy

Back 505

for low energy RBE ~ 10 (5-15); for high energy ~2

Front 506

what causes obstruction of intestinal tract following irradiation

Back 506

fibrosis

Front 507

is basic fibroblastic growth factor anti or pro apoptotic

Back 507

anti-apoptotic

Front 508

what cells have pro-apototic tendency

Back 508

serous acinar cells, oocytes, crypt cell and lymphocytes

Front 509

egfr activation - pro or anti apoptotic

Back 509

anti-apoptotic

Front 510

PI-3K - pro or anti apoptotic

Back 510

pro-apoptotic

Front 511

TNFR-1, Fas/CD95, TRAIL receptors

Back 511

extrinistic pathway for apoptosis;

Front 512

DNA-PK, ATM, ATR, mTOR are all part of what family

Back 512

PIKK family

Front 513

farnyltransferase has what relation to RAS

Back 513

stimulate (so there is a push for farnyltransferase inhibitors which inhibits ras)

Front 514

is ras involved in ATM activation

Back 514

NO

Front 515

ras is pro or anti cell cycle

Back 515

PRO; via Raf-Mek-MapK/erk pathway (leads to more cyclin D1 expresion);
Ral GDS (inhibits apoptosis)
JND (inhibits p53)

Front 516

mTOR - pro or anti cell survival

Back 516

pro survival
use inhibitors to radiosensitize and slow growth (- limus)

Front 517

MDM2, COP1, PIRH2, JNK

Back 517

all down regulate p53

Front 518

14-3-3σ and GADD45

Back 518

inhibit CDK1 - cyclin B --> G2 arrest (both are activated by p53)

Front 519

cdc25c

Back 519

activates CDK1-cyclin B

Front 520

chk1/chk2

Back 520

activates p53; also inhibits cdc25A

Front 521

tumor suppressor or oncogene: PTCH

Back 521

tumor suppressor (gorlin - skin, medullo)

Front 522

tumor suppressor or oncogene: CDKN2A

Back 522

tumor suppressor (melanoma)

Front 523

tumor suppressor or oncogene: MEN1

Back 523

tumor supp (parathyroid, pituitary, islet)

Front 524

tumor suppressor or oncogene: NF2

Back 524

tumor supp (meningioma, acoustic neuroma)

Front 525

tumor suppressor or oncogene: MET

Back 525

oncogene

Front 526

tumor suppressor or oncogene: ABL

Back 526

oncogene

Front 527

tumor suppressor or oncogene: BRAF

Back 527

oncogene

Front 528

tumor suppressor or oncogene: myc

Back 528

ONCOGENE

Front 529

tumor suppressor or oncogene: MDM2

Back 529

oncogene

Front 530

order of decrease for CBC (granulocytes, platelets, erythrocytes, lymphocytes)

Back 530

lymphocytes > granulocytes > thrombocytes > erythrocytes

Front 531

what organ is the least tolerant to re-treatment; and show least recovery following RT

Back 531

kidney

Front 532

Survival curves with small alpha/beta ratios are expected to have curve shapes best described by

Back 532

Curves will have a flat initial slope followed by a steep terminal slope

Front 533

cdc2

Back 533

The cdc2 protein is a kinase that phosphorylates serine and threonine residues in target proteins and combines with cyclin A and B in order to undergo a conformational change to activate the kinase site of the cyclinB-cdc2 complex.

Front 534

Which proteins are part of the apoptosome?

Back 534

Apaf-1, cytochrome c, and caspase 9

Front 535

bcl-xs - pro or antiapoptotic

Back 535

pro-apoptotic

Front 536

relationship btw PARP and apoptosis

Back 536

The overactivation of PARP may deplete the stores of cellular NAD+ and induce a progressive ATP depletion, since glucose oxidation is inhibited, and necrotic cell death. In this regard, PARP is inactivated by caspase-3 cleavage (in a specific domain of the enzyme) during programmed cell death.

PARP is found in the cell’s nucleus. The main role is to detect and signal single-strand DNA breaks (SSB) to the enzymatic machinery involved in the SSB repair. PARP activation is an immediate cellular response to metabolic, chemical, or radiation-induced DNA SSB damage.

incresing PARP activity correlates with increas apoptosis

Front 537

p14

Back 537

The gene product p14 binds to mdm2 protein and prevents ubiquitination of p53 protein. The result is the stabilization of p53 protein and ultimately an increase in its concentration. Therefore, p14 functions as a tumor suppressor by inhibiting the inhibitor of p53.

Front 538

what is the expected cell loss factor for a slow recovery tissue versus a high growth tumor

Back 538

slow recovery - high cell loss factor (approximates to 1)
high rate of growth - low cell loss factor

Front 539

with acute hyperthermia > 45 degrees do you see a change to the shoulder? What about with 40-43 degrees?

Back 539

steepening of xray survival curve; no change to shoulder

with lower temperature: removal of shoulder

Front 540

Electrophoretic mobility shift assay (EMSA)

Back 540

feed in fragments of DNA that resemble promotor and then radioactive labeled then mix with cell lysate (bunch of protein) then run on gel; then if protein attaches then can see shift in gel runing;

monitors protein that binds to DNA

Front 541

Rnase protection assay

Back 541

assess binding of proteins to RNA to prevent nuclease cleavage

Front 542

can RT-PCR be used to assess gene expression

Back 542

yes

Front 543

two-hybrid screen looks at what

Back 543

protein protein interaction

Front 544

which can u use the whole genome for : RT PCR or expression array

Back 544

expression array

Front 545

2D gel electrophoresis - dna or protein

Back 545

protein

Front 546

bind to and inhibit the transcription of specific genes and/or they can silence cytoplasmic mRNAs by inhibiting translation ; sized 25 nucleotide

Back 546

siRNAs and miRNAs

Front 547

whats denser polyactrylamide gels versus agarose gels? Which is used for small DNA?

Back 547

polyacrylamide (used for fine separation)

Front 548

ELISA

Back 548

well plates; want to measure cytokines or other proteins - antibody in the well plates put in the serum of patient

another antibody will be added that binds if there is a primary antibody-protein interaction

Front 549

subtractive hybridization input

Back 549

compares amounts of mRNA in different samples

Front 550

is the RNA transcribed from DNA translated directly on the ribosome

Back 550

no it undergoes the first step to go from RNA of whole genome to post processing to remove introns

Front 551

Dnase I footprinting

Back 551

assess binding of proteins to DNA to prevent nuclease cleavage

Front 552

transfer of a genet to a mutant cell in order to determine whether doing so restores the normal phenotype

Back 552

functional complementation

Front 553

what interaction does phage display

Back 553

protein-protein

Front 554

what wavelength is considered ionizing

Back 554

10^-7 (less than 10^-6)

Front 555

which of the following are sensitive to XRT: XP, Cockaynes, Werners, Blooms, HNPCC

Back 555

trick; none

Front 556

if 2 cell lines with difference alpha/beta ratios have the same D10 for a single dose. What would you expect the change in D10 if you fractionated it (assuming alpha beta was low for 1 and high for the other)?

Back 556

the low alpha beta D10's would increase
the high alpha beta would not change

Front 557

how does OER change for high doses? For low dose rate?

Back 557

for high doses - OER increases (oxygen more effective for high doses - ie more resistant part of curve)

for low dose rate - OER decreases (on the alpha portion of the curve - oxygen not doing much)

Front 558

how do u calculate the % hypoxic cells in a tumor using animals

Back 558

SF of air breathing animals / SF of nitrogen breathing animals

Front 559

what does hypoxia do to p53?

Back 559

apoptosis of p53 wild type cells, gene amplification, genomic instability in p5# mutated cells and increased metastatic potentials (increas in p53 mutant cell pop w/ hypoxia because wild type die via apoptosis

Front 560

which of the following is a pure beta emitter : I-131 or Y-90

Back 560

Y-90 (zeralin)

Front 561

in the dilution assay how do you calculate the survival faction of the irradiated cells using the TD50 (total dose/# of cells to infect 50% of the recipient animals)

Back 561

TD50 control / TD 50 irradiated

Front 562

epo trials demonstrated what affect on cancer patients survival

Back 562

deleterious

Front 563

18F perfluorocarbon emulsion is used to assay what?

Back 563

tumor blood flow

Front 564

if growth fraction = 1 then what does Tpot equal to? If GF = 0?

Back 564

GF = 1 (Tpot = Tc)
GF = 0 (Tpot = infinity)

Front 565

are mTOR inhibitors radiosensitizers

Back 565

yes

Front 566

ATM's control of check points through what mediators: G1/S, G2/M, and S phase

Back 566

G1/S - inhibition of MDM2, activation of p53 and Chk2/1
G2/M - activation of Chk2/Chk1, p53 and inhibition of MDM2
S phase - Nbs1 and SMC1

BRCA1 is a substrate as well

Front 567

most radiosensitive cell class in Casarett system? Rubin

Back 567

Casarett
vegetative intermitotic -> diff intermit -> rever post-mitotic -> fixed post-mitotic

Rubin
undiff stem -> stem -> reverting mature -> fixed/functional mature

Front 568

CNS changes post radiation affect gray or white matter

Back 568

white; demyelination, vasculopathies, necrosis

Front 569

when is radiation pneumonitis seen? Fibrosis?

Back 569

1-6 months for pneumonitis; 6 months for fibrosis

Front 570

when boron is irradiated with neutron what are the products

Back 570

lithium and alpha particles

Front 571

amsacrine - topo I or II

Back 571

II (just like etoposide)

Front 572

in a isobologram analysis what does the straight line represent

Back 572

additive; below represents synergism; above reflect anatgonism

Front 573

use of pentoxyfylline

Back 573

prevent radiation induced fibrosis

Front 574

most common cancer seen in chernobyl? Japanese A-bomb? Marshall islands? Tonsils?

Back 574

chernobyl thyroid
japan - bladder?
marshall island - thyroid
tonsil: thyroid

Front 575

leukema vs solid - which follwos the linear quadratic absolute risk

Back 575

leukemia ; (solid - linear relative risk model - base rate multiplied by relative risk)

Front 576

at what age does the fetus take up iodine

Back 576

10 weeks

Front 577

how much (%) does radon take of annual effective dose? Nuclear medicine? Natural background (minus radon)?

Back 577

radon 30%; nuclear 0.14 mSv; natural (- radon) : 1 mSv

diagnostic 3 mSV

Front 578

for emergency dose should not exceed

Back 578

500 mSv

Front 579

LET value for neutrons (energy average)? LET for 250 kv x-rays? 150 Mev protons?

Back 579

100 neutrons; 2 (250 kvp x-rays; 0.5 (protons)
units: keV/micrometer

Front 580

the tunel assay is used for detecting what?

Back 580

apoptosis (specifically DNA fragmentation) - deoxynucleotidyl transferease mediated deoxyuridine triphosphate nick end labeling

Front 581

what does BOLD MRI imaging detect

Back 581

changes in paramagnetic deoxyhemoglobin which represents a very noninvasive measurement of hypoxia (BOLD - blood oxygen level dependent)

Front 582

tissues with high capacity for clonogen migration from outside the irradiation field tend to be those that have FSUs arrange in _____( series or parallel) or those structurally ____ (defined or undefined)

Back 582

series (intestinal epithelim, spinal cord)
undefined (skin)

Front 583

whats the diff btw ion pair and free radical

Back 583

ion pair represents electron and free radical whereas free radical is the unpaired electron molecule alone

Front 584

with increasing dose of radiation the formation of DSBs becomes more linear or linear quadratic

Back 584

with high enough dose becomes linear

Front 585

when are chromosome/chromotid abnormalities observed? What's one example of an abnormality that could be observed in interphase?

Back 585

majority seen in mitosis; exception is micronuclei which result from acentric fragment that cell forms nuclei

Front 586

with a cell line with a large "n" what would happen to D0 if I increase fraction size

Back 586

it would decrease

Front 587

is mental retardation induction deterministic or stochastic

Back 587

deterministic

Front 588

if deficient in MRE11 what disease? BLM helicase? WRN helicase? A-G mismatch/BRCA2? Artemis?

Back 588

MRE11 - ataxia-telangiectasia-like disorder
BLM - bloom's
WRN - werner's
A-G mismatch/BRCA2 - fanconi's
Artemis - SCID

Front 589

in regions of hypoxia describe what happnes to functional lymphatics and interstitial fluid pressure

Back 589

decreased lymphatics
increased interstitial fluid pressure

Front 590

in absence of angiogenesis tumors would be expected to only reach a diameter of …

Back 590

2 mm

Front 591

hypoxia has what affect on BRCA1

Back 591

repressed (leads to less DNA repair HRR); still hypoxia activates RAD51

Front 592

what happens to the cell loss factor after the start of radiotherapy

Back 592

appears to decreas --> slowing tumor regression

Front 593

MAPK and PI3K are both dounstream targets of what

Back 593

RAS signaling; results in cell viability

Front 594

would RFLP be useful in gene expression?

Back 594

no because only measures change in DNA base sequence

Front 595

RAF, MEK, JNK, RAC/RHO, PLC and Pi3k/AKT

Back 595

Ras targets

Front 596

wortmanin is a ____ inhibitor

Back 596

PI3K

Front 597

what do I have to take a tumor down to with regards to clonogenic cells to have the chance of cure to be 37%

Back 597

10^0 = 1

Front 598

are patients with deficient NER characterized by cancer proneness? What are the 2 prototype diseases?

Back 598

NO; XP and cockaynes

Front 599

viruses that can inactivate p53 include…

Back 599

HPV, SV40, and adenovirus ( NOT EBV)

Front 600

how is p53 activated in response to DNA damage

Back 600

phosphorylation or acetylation

Front 601

what is the threshold for the emeitc response of RT? Detectable change in blood count?

Back 601

1 Gy

Front 602

onset of vomiting can be used as a indicator of life-threatening whole body RT; what time frame do u use?

Back 602

within 4 hours indicates life threatening dose

Front 603

who is more sensitive to induction of radiation induced sterility - younger or older women

Back 603

older women.

Front 604

the most radiosensitive cells in the heart are…

Back 604

the vascular endothelial cells

Front 605

order these in terms of dose (and time to onset) - temp erythema, moist desquamtion, dry desquamation, temporary and permanent epilation

Back 605

2 Gy - 1 day - temporary erythema
3 Gy - 3 weeks - temp epilation
7 Gy - 3 weeks - permanent epilation
14 Gy - 4 weeks - dry desquamation
18 Gy - 4 weeks - wet desquamation

Front 606

what types of drugs can be used to treat radiation nephropathy

Back 606

ACE inhibitors

Front 607

what is the life span of mature spermatids

Back 607

67 days

Front 608

TGF beta - has a ____ effect on epithelial cell proliferation

Back 608

inhibitory; but increases prolif of mesenchymal cells and extracellular matrix and involved in radiation fibrosis

Front 609

the TD5 of the cspinal cord as a function of length changes how

Back 609

initially decreases with increasing cord length, then remains relatively constant

Front 610

in the kidney, the tolerance to retreatment ______ (increases or decreases) with time; with treatment how does kidney differ from other tissues with regards to inflammation

Back 610

decreases (which indicates continous progression of renal injury)

does not experience increase in inflammatory cells

Front 611

how does photodynamic therapy work? Is it toxic to hypoxic cells?

Back 611

photosensitizing agent, oxygen and light ; agent - hemotoprophyrin; light wavelength is 600-900 nm

not efficacious to hypoxic cells

Front 612

what drug class mediates synthesis of eiconsanoids from arachidonic acid

Back 612

COX-2 inhibitors

Front 613

tipifarnib mechanism of action

Back 613

inhibitor of farnesyl transferase

Front 614

why is bleomycin more toxic to oxygenated cells than to hypoxic cells

Back 614

role of molecular oxygen; redox reactions involving metas and O2

Front 615

whats a pro drug (versus bioreductive drugs)

Back 615

hypoxic cell sensitizers are bioreductive meaning they get converted in hypoxic cells

prodrugs get converted in the liver (amifostine)

Front 616

what drug has been used to reduce the incidence and severity of oral mucositis?

Back 616

palifermin (keratinocyte growth factor); amifostine has shown to reduce the incidence xerostomia (not oral mucositis)

Front 617

overgaards metaanalysis of hypoxic cell radiosensitizers or oxygen showed what

Back 617

improvement of survival and tumor control

Front 618

what phase does hydroxurea work in

Back 618

s phase

Front 619

estimated risk for a mutation being produced in the child of an irradiated individual is…

Back 619

0.2 % per SV

Front 620

CGH arrays are used for genome-wide detection of chromosomal gains or losses

Back 620

….

Front 621

genomic DNA arrays can be used to study epigenetic changes; low abundance RNAs cannot be used because of high background signals; expression profiles btw cancer and normal cells differ by a lot; they are subject ot inconsistencies

Back 621

….

Front 622

1 Gy of irradiation to the testis results in a nadir of sperm count at ___ months

Back 622

2

Front 623

G2 block is what minute per cGy

Back 623

1 min / cGy

Front 624

Dicentrics
- dose for low LET radiations delivered at a high dose rate
- dose for low LET radiations at low dose rate

Back 624

linear-quadratic - low LET deliverate at a high dose rate
linear - low LET at low dose rate

Front 625

as age increases active bone marrow is increasingly located in the ______ (axial or appendicular)

Back 625

axial

Front 626

nimarozle best for single or mult fraction

Back 626

single - reoxygenation leaves drug useless

Front 627

hierarchical tissue - what accounts for most acute RT effects

Back 627

stem cell depletion

Front 628

minium dose at 2 Gy/fx causes late kidney toxicity (nephropathy)

Back 628

25-30 Gy

Front 629

wither's head and neck extra dose to combat repopulation in H&N

Back 629

0.6 Gy (60 cGy/day)

Front 630

the single-hit, multitarget model does not provide a good fit for (low or high) radiation doses

Back 630

high doses (overestimates)

Front 631

exposing post irradiation cells to saline versus drug that prevents cell cycling does what to PLD

Back 631

fixation of PLD in the drug treated cells which results in lower SF

Front 632

bleomycin works in hpoxic or oxgenated cells

Back 632

increases damage fixation in presence of oxygen

Front 633

clonogenic cell survival is defined as the ability of cells to form colonies of at lease ___ cells

Back 633

50

Front 634

proton therapy has higher or lower integral dose

Back 634

lower integral dose

Front 635

mechanism of action for tirapazamine

Back 635

hypoxic cells reduce TPZ -> free radicals
generation of DNA DSB
interference with DNA replication

poisinging of topo II

Front 636

annual total effective dose limit to an individual member of the general public is…

Back 636

1 mSv

Front 637

gemcitabine mechanims of action

Back 637

cytidine analogue competes for uptake (inhibits DNA polymerase and ribonucleoside reductase)

when mismatch genes inactive - abolishes cytotoxic and radiosensitizing effect of gem

Front 638

dose rate effect is most pronounced at what dose range

Back 638

.01 - 1 Gy / min
1 - 100 cGy / min

Front 639

dirty bomb in large city uses what estimate for fatal cancers

Back 639

5.0 x 10^-2 cancer/SV

Front 640

survival curve of population of cells with hypoxic sells demonstrates a break in the curve; the curve demonstrates a shallow or steeper slope and a lower or higher D0

Back 640

Do is higher reflecting increased resistance and the slope is shallower

Front 641

annual effective dose from radon gas

Back 641

2 mSv

Front 642

how do PARP inhibitors work

Back 642

PARP1 is a protein that is important for repairing single-strand breaks ('nicks' in the DNA). If such nicks persist unrepaired until DNA is replicated (which must precede cell division), then the replication itself will cause double strand breaks to form.[citation needed]

classic cleaved target apoptosis

Drugs that inhibit PARP1 cause multiple double strand breaks to form in this way, and in tumours with BRCA1, BRCA2 or PALB2 [6] mutations these double strand breaks cannot be efficiently repaired, leading to the death of the cells. Normal cells that don't replicate their DNA as often as cancer cells, and that lacks any mutated BRCA1 or BRCA2 still have homologous repair operating, which allows them to survive the inhibition of PARP.[7][8]

Some cancer cells that lack the tumor suppressor PTEN may be sensitive to PARP inhibitors because of downregulation of Rad51, a critical homologous recombination component, although other data suggest PTEN may not regulate Rad51.[3][9] Hence PARP inhibitors may be effective against many PTEN-defective tumours[4] (e.g. some aggressive prostate cancers).

Front 643

whats a weaker carcinogen radiation or chemo

Back 643

generally radiation

Front 644

late-responding normal tissues have shallower initial slopes than for early-responding tissues

Back 644

…

Front 645

what is mitotis promoting factor

Back 645

cylin B/cdk1

Front 646

where is ras located and what happens after farnelystransferase gets hold of it

Back 646

ras located in cytoplasm; following farnelysation --> goes to cell membrane

Front 647

OER in low dose rate vs high dose rate

Back 647

2 vs 3 Gy

Front 648

cachexia is assoc with what cytokine

Back 648

TNF- alpha

Front 649

the higher the LET what is more likely spurs , blobs, or short track

Back 649

track

Front 650

when spurs, blobs and short tracks overlap, this results in…

Back 650

multiply damaged sites (clustered lesions)

Front 651

minimum dose detected by dicentrincs in lymphocytes is

Back 651

25 cGy

Front 652

how can acentric fragments be used to estimate dose

Back 652

by looking for micronuclei

Front 653

in HRR what complex causes the initial incision and removal to create a single-stranded region

Back 653

rad50-mre11-nbs1 complex

Front 654

in NHEJ what binds to the broken DNA ends

Back 654

KU70/80

Front 655

in NHEJ what has endo/exo nuclease activity to pair away regions of mismatch in the microhomology hydrogen bonding that leaves some single stranded ends

Back 655

artemis

Front 656

PARP, DNA glycosylase, AP endonuclease, DNA plymerase Beta, ligase III, and XRCC1 are involved in what

Back 656

Base Excision Repair

Front 657

Lig 4, ATR-Sekel, RS-SCID and AT-like disorder (MRE 11) are syndromes in which individuals are radio _____ (sensitive vs resistant)

Back 657

sensitive

Front 658

what is the predominant process for DSB repair in human cells?

Back 658

NHEJ

Front 659

what corrects interstrand crosslinks

Back 659

recombinational repair (HRR, or NHEJ)

Front 660

what corrects AG/TC mismatch, insertion, deletion

Back 660

mismatch

Front 661

when does D0 = D37

Back 661

when there is no shoulder or n=1; survival follows single hit kinetics

Front 662

what phase does apoptosis often occur in

Back 662

interphase (G0)

Front 663

which pathway results in release of cytochrome C from the mitochondria

Back 663

intrinisic pathway -- cyt C then combines with pro-caspase 9 and ATP in the apoptosome resulting in the formation of active caspase 9

Front 664

paired survival curve in which animals are irradiated eitehr while breathing air or under hypoxic conditions looks like what

Back 664

y axis - logarithmic fx of cells; x axis - dose
steep portion initially (aerobic cells dead) then a break where there is a shallow portion that reflects the hypoxic cells
by extrapolating back to the y-axis can estimate the percent hypoxic cells

Front 665

which is a pure beta emitter: 90Y or 131I

Back 665

90Y (Zevalin)

Front 666

in the percent labeled mitoses approach with time to 50% point represents what?

Back 666

G2 + 0.5M
TG2 + 0.5 Tm

Front 667

(ln2)(Tc) / ln(1+GF)

Back 667

Tpot

Front 668

what does Tpot assume cell loss factor to be

Back 668

Missing Answer

Front 669

what viruses can result in inhibition of p53

Back 669

SV40 large T antigen, papillomavirus E6 protein and adenovirus E1B

Front 670

TRK - oncogene/tumorsupressor

Back 670

oncogene

Front 671

MDM2 - oncogene/tumor supressor

Back 671

oncogene

Front 672

VHL, PTCH, CDH1, APC, CKDN2A (p16INK4A and P14ARF), MEN1, SMAD 4, and NF2 - all share what

Back 672

tumor supressors

Front 673

are oncogenes inherited in a pedigree

Back 673

rarely since generally lethal (mutation dominant though)

Front 674

BRAF oncogene is assoc with what type of cancer

Back 674

melanoma

Front 675

epigenetic regulation via DNA methylation, histone deacetylation and gene silencing through miRNA is important for…

Back 675

silensing genes (tumor supressors ; NOT oncogenes)

Front 676

p16INK4a and p14ARF function by promotin what

Back 676

retinoblastoma (RB) and p53 transcription factor respectively

p16INK4a inhibits cyclin D dependent kinases - CDK 4 and 6

p14ARF antagonizes the function of p53 negative regulator, MDM 2

Front 677

SMC1 - is it pro or anti cell cycle

Back 677

anti cell cycle stimulated by ATM via Nbs1

Front 678

prodromal TBI reflect 0.5-1Gy dose
easy fatigability, anorexia, nausea and vomiting

vs fever, hypotension, immediate diarrhea

Back 678

low vs high doses

Front 679

what happens to latent period if u increase dose

Back 679

decrease latent period

Front 680

what type of tissue is sensitive to large dose to a small volume: serial or parallel

Back 680

serial

Front 681

edema in the alveolar wall, infiltration by mononuclear cells and macrophages, and desquamation of the alveolar epithelium all characterize what

Back 681

lung fibrosis (occurs > 6 months)

Front 682

anemia, azotemia and increased blood pressure characterize what

Back 682

radiation nephropathy ()

Front 683

what is the main way to spare the parotid

Back 683

decrease the volume irradiatied (since fractionation results in relatively little sparing)

Front 684

spinal cord myelopathy involves what cells

Back 684

endothelial cells, oligodendrocytes and macrophages

Front 685

gonadal endocrine function of the testes occurs at what dose range

Back 685

20-30 Gy

Front 686

the radiobiological target of the testes is identified as what

Back 686

type B spermatogonia

Front 687

BED tumor experimental / BED tumor standard // BED complications experimental / BED complications standard

Back 687

therapeutic ratio

Front 688

actinomycin D concurrent with radiation - causes toxicity of what organ

Back 688

lung

Front 689

what drug is used to prevent radiation-induced fibrosis

Back 689

pentoxifylline

Front 690

contrast the toxicity of hypoxic cell radiosensitizers vs halogenated pyrimidines

Back 690

hypoxic cell radiosensitizers - peripheral neuropathy (-azoles)
halogenated pyrimidines - photosensitivity (- deoxyuridine)

Front 691

drugs ending in -nib versus -mab

Back 691

nib - small TKI
mab - monoclonal antibody

Front 692

ixabepilone works by what

Back 692

binds to tubulin and promotes tubulin polymerization and microtubule stabilization, theraby arresting cells in the G2-M phase of the cell cycle

Front 693

nelarabine works by how

Back 693

antimetabolite - ara-G; disrupts DNA synthesis and induces apoptosis

clofarabine - inhibits ribonucleotide reductase

Front 694

romidepsin is an examble of what type of drug? Mechanism of action?

Back 694

histone deacetylase inhibitor; results in hyperacetylation of histones which affects gene expression (since for expression cell must control the coiling and uncoiling of DNA around histones)

Front 695

fulvestrant works how?

Back 695

targets and degrades the estrogen receptors present in breast cancer cells (faslodex)

Front 696

abarelix works how?

Back 696

inhibits gonadotropin and related androgen production by directly and competitievely blocking receptors in the pituitary gland. Directly suppresses luteinizing hormone and follicle stimulatin hormone secretion and thereby reduces tesosterone

Front 697

transducing tumors cells with cDNA with TNF and promoter for EGR which is turned on by the active oxygen species produced by radiation

Back 697

radiogenetic therapy - radiation-inducible gene linked to a cytotoxic agent

Front 698

cut offs used for 4-5% per SV versus 8-10% in risk of radiation-induced cancer

Back 698

< 0.2 Sv or dose rate less than 0.1 SV/hr

Front 699

txt of ankylosing spondylitis resulted in what type of cancer

Back 699

leukeumia (NOT CLL)

Front 700

does treatment with radioactive iodine cause increase in 2nd malignancies

Back 700

no; has not been seen

Front 701

when leukemias and solid tumors appear following irradiation in comparison to the general population

Back 701

leukeumas appeared few years after irradiaiton but solid tumors appeared at same age as occurs spontaneously

Front 702

are humans more sensitive to radiation than mice

Back 702

no

Front 703

was there an increase in genetic effects in children of A-bomb survivors

Back 703

no

Front 704

fetus begins to take up iodine at what age

Back 704

10 weeks

Front 705

what relation does thalidomide and angiogenesis have?

Back 705

thalidomide is inhibitor of angiogenesis

Front 706

what pathway does CAK have to do with

Back 706

p53 pathway -> p21 -| CAK (CAK normal stimulates cdc2 and cyclin B)

Front 707

when does the effective dose equal the equivalent dose

Back 707

under conditions where the whole body is irradiated

Front 708

does background radiation increase or decrease with altitude

Back 708

increase with increasing altitude

Front 709

if I increase initial heat dose will I get more or less thermotolerance

Back 709

more

Front 710

from the Japan population what is the estimated risk of fatal cancer

Back 710

8% per SV

Front 711

what is SDS detergent used for

Back 711

to denature proteins