Cancer 201 - Barsky Flashcards
1
Q
T/F: cancer incidence is synonymous with cancer mortality
A
false; highest incidence is prostate and breast for M and F but lung is the highest killer of both
2
Q
(Carcinoma/sarcoma) causes 99% of all cancers
A
carcinoma
3
Q
What tissue does carcinoma arise from?
A
epithelial tissue
4
Q
what tissue does sarcoma arise from?
A
mesenchymal tissue
5
Q
The increase in smoking in men in women post WWII with mortality increasing from the 70-90s, decades after the increase shows what property of cancer?
A
latency
6
Q
What has caused the decrease in colorectal and prostate cancer?
A
better screening and regular colonoscopies
7
Q
What test has reduced the risk of cervical cancer?
A
Pap smear
8
Q
What four things does a flat line across an age-adjusted mortality chart tell you about that type of cancer?
A
- No good Tx for met. disease
- No good screening
- No decrease in incidence
- No good chemo-prevention
9
Q
What caused the apparent “increase” in prostate and breast cancer in the early 90s?
A
better screening
10
Q
Define the multi-hit theory of cancer development?
A
It takes numerous mutations over a lifetime to develop cancer
11
Q
If cancer were dependent solely on rate of cell turnover, where would we see the most cancer? Since we don’t see that, what does it tell us?
A
Neonates and fetuses; that cancer is caused by more than just cell turnover
12
Q
After a transformation event, what is the classification of a precancer cell?
A
tumorigenic
13
Q
What takes a tumorigenic cell to an invasive cell?
A
selection pressure
14
Q
Mutations, rearrangements, or amplifications of (blank) genes leads to tumor progression
A
proto-oncogenes
15
Q
Reduction of (blank) of tumor suppressor genes caused by deletions or mutations also leads to tumor progression
A
homozygosity
16
Q
What two types of epigenetic changes within promoters regulate cancer gene expression?
A
methylation and histone deacetylase statuses
17
Q
Cancer is characterized by a (blank and blank) imablance
A
methylation and histone deacetylation
18
Q
In terms of prevention, what does the multihit theory promote?
A
early screening and detection
19
Q
(blank) explains why cancer is a disease of aging
A
multi hit theory
20
Q
T/F: Cancer is a function of cell division
A
false
21
Q
What type of cancers are completely curable via surgical resection?
A
carcinoma in situ–no invasion to lymphatics so you cut it out and its alllll gone
22
Q
What explains the fact that most cancer happens after the age of procreation?
A
Since we’ve already had kids there was no selection pressure to cause us to develop a defense against it
23
Q
What are the four defining properties of cancer?
A
- uncontrolled growth
- invasion and metastasis
- clonal dominance
- loss of differentiation
24
Q
If tumors are monoclonal, then why can’t we cure cancer with a targeted agent?
A
tumors become heterogeneic via mutant subclones
25
Mutant subclones in tumors are heterogenous with respect to (blank x 4)
invasiveness, metastatic ablility, antigenicity and responsiveness to chemotherapy
26
What are the four classes of cancer treatment?
1. surgery
2. chemotherarpy
3. radiation
4. immunotherapy
27
T/F: The monoclonality of cancer means all cancer cells are identical
false
28
The lack of specific antigen, tumor cell heterogeneity, and micrometastais are all (blanks) in treating cancer
limitations
29
T/F: most 1st time diagnoses of cancer are not early enough to prevent micrometastasis
true :(
30
What is the lower limit for detectable cancer cells and what does this mean clinically?
fucking 1 million cells! means that even if the test is negative you have more than enough to fucking throw mets everywhere.
31
What are the etiologies/causes of cancer?
```
environmental carcinogens
UV radiation
ionizing radiation
viruses
lifestyle, diet, immune status
hereditary factors/genes
unknown
```
32
What is the most common etiology of cancer?
unknown
33
Do direct or indirect chemical carcinogens activate the CYP450 system?
indirect--activation makes them a carcinogen
34
Chemical carcinogens are (nucleophiles/electrophiles). What does this mean about how they work?
Electrophiles; bind to the positive charge of DNA
35
When describing chemical carcinogens, (blanks) start the carcinogenic response while (blanks) accelerate it
initiators, promoters
36
Does an initiator or promoter bind directly to DNA and cause a mutation?
initiator
37
Promoters have (genetic/epigenetic) mech of action?
epigenetic
38
What is the result of promoter action?
promotes cell division to pass on mutations caused by initiators
39
What enzymees regulate initiator and promoter carcinogenicity?
phase I--CYP450
| phase II--conjugation
40
T/F: carcinogenicity of DNA adducts is location dependent
true
41
Radon is a form of (blank) radiation
ionizing
42
How does ionizing radiation damage DNA?
forms DNA adducts
43
How does ionizing radiation differ in the way it damages DNA from chemical carcinogens?
ionizing radiation causes single and double stranded DNA breaks
44
What damage does ionizing and UV radiation cause?
csome breaks, translocations, and point mutations
45
What type of radiation leads to skin cancer?
UV
46
Pts with xeroderma pigmentosum are at an increased risk of skin cancer from what?
UV radiation
47
9% of children exposed to radiation develop what type of cancer?
thyroid
48
HPV 1,2,4,7 cause what?
papillomas or warts
49
What HPV strains cause cancer?
16 and 18
50
HPV 16 and 18 cause what type of cancer?
invasive squamous cell carcinoma
51
T/F: HPV 6 and 11 have high malignant potential
false; low
52
Early gene products (blank and blank) from HPV inhibit the two suppressor genes (blank and blank)
E6 and E7 inhibit TP53 and RB
53
T/F: full malignant potential of HPV is acheived through viral infection alone
false; requires environmental factors
54
What are the four tumor types associated with EBV?
1. Burkitt's lymphoma
2. B cell lymphoma in AIDS
3. Hodgkin's disease
4. Nasopharyngeal cancer in S. China
55
What cancer is associated with the translocation(8:14) - MYC gene?
Burkitt's lymphoma
56
In nonendemic areas, what percent of the pop is infected with eBV?
20%
57
What type of cancer has the highest association to a viral infection? What is the virus that causes it?
99% of hepatocellular cancer is caused by Hep B
58
T/F: infection with Hep B is sufficient to reach the full malignant potential
false; multifatorial
59
injury and regeneration of the liver predispose one to mutations caused by (blank)
environmental agents; your liver is what detoxes what you take in!
60
What viral protein disrupts growth control by activating proto-oncogenes and inactivating TP53 in the liver?
HBx protein from HBV
61
Immunodeficient pts have a higher rate of what two classes of cancer?
lymphomas and virally induced
62
What are some of the lifestyle factors that influence cancer dev?
Women who are sexually promiscuous have a high rate of cervical cancer
Women who are nulliparous have a high rate of breast cancer
Men who are obese have a higher rate of cancer of the esophagus
Women who eat fatty foods have a higher rate of breast cancer
Men who drink alcohol and smoke have a higher rate of head and neck cancer
People who eat red meat may have a higher incidence of colon cancer.
63
T/F: Correlation can be causation, you just can be sure about it
true
64
Many cancers have a familial component while few cancers have a (blank) component to be inherited
germline
65
P53 Li Fraumeni, BRCA1/2, Lynch Syndrome, and Retinoblastoma are all examples of (familial/germline) cancers
germline
66
(blank) codes for poducts associated with neoplastic formation
oncogenes
67
T/F: oncogenes are regulated by normal growth factors and signals
false
68
(blank) are normal genes that affect growth and differentiation
proto-oncogenes
69
Retroviral transduction( v-oncs) and changes in situ converting them to c-oncs are (blank)
proto-oncogenes
70
RAS mutations are (blank) mutations
point
71
chromosomal (blank) is when part of the chromosome is moved near a promoter or chimeric gene product
translocation
72
N-MYC neuroblastoma and HER-2 breast carcincoma are examples of gene (blank)
amplification
73
What are the five basic categories of oncogenes?
1. growth factors
2. growth factor receptors
3. signal transduction proteins
4. nuclear transcription factors
5. cyclins and cyclin dependent kinases
74
Active kinases control what part of the cell cycle?
G1 to S transition
75
When is cyclin D first phosphorylated?
at the beginning of G1
76
When is Rb phosphorylated?
G1 to S transition
77
During G2, M, and the beginning of G1, cdk is (active/inactive)
inactive
78
Gene products that suppress cell proliferation include:
growth inhibitory factors
cell adhesion
signal transduction
nuclear transcription and cell cycle
79
what is the guardian of the genome?
TP53
80
What is one of the most commonly mutated genes and is seen in almost all human cancer?
TP53
81
What are the two major functions of TP53?
antiproliferation and apoptosis
82
TP53 senses DNA damage and halts the cell in what part of the cell cycle to allow for DNA repair?
G1
83
increase of CDK1 p21(CDKN1A) prevents phosphorylation of what?
Rb
84
Induction of GADD45 by TP53 aids in what?
DNA repair
85
If TP53 cannot fix DNA what apoptosis gene is induced?
BAX
86
Li Fraumeni is caused by inheriting one mutant of (blank or blank)
TP53 or RB
87
T/F: Li Fraumeni puts you at an increased risk of metastasis of a single malignancy
false; risk of multiple types of malignancies
88
What viruses can deactivate TP53?
HPV, HBV, EBV
89
What gene is associated with childhood retinoblastoma?
RB
90
What is the percentage breakdown of the methods of acquiring RB?
40% familial, auto DOM
| 60% sporadic
91
What is the special case of multi-hit theory for RB? How is it different in inherited forms?
Needs 2 hits; one to take out each copy of the the gene. In inherited forms, one copy is already bad, so you only need one hit to get it
92
What type of sarcoma do you have an increased risk of getting if you have RB?
osteosarcoma
93
Homozygous mutation in both p53 and RB genes causing cancer is an example of (dominant/recessive) action
recessive, need both!
94
Failure of only one oncogene allele is sufficient to cause cancer is an example of (recessive/dominant) action
dominant
95
What types of collagen are present in the stroma?
collagen I and III
96
what type of collegen is found in the basement membrane of the vascular channel?
collagen IV
97
The active migration of neoplastic cells out of their tissue origin and across host tissue boundaries is defined as (blank)
Cancer invasion
98
What are the two criteria that define a metastasis?
1. secondary tumor colony discontinuous from the primary tumor
2. must arise from a tumor cell translocated from the primary tumor
99
Cancer must get into the circulation then (blank) to a secondary location to cause metastasis
egress
100
T/F: invasion is synonymous with metastasis
false!!!
101
what type of vasculature does carcinoma normally spread through?
lymphatics
102
what type of vasculature does sarcoma normally spread through?
blood vessels
103
What are the three routes by which a neoplasm can metastasize?
1. lymphatic spread
2. hematogenous spread
3. transcoelomic seeding
104
What organs are involved in hematogenous spread?
lung, liver, brain, bone marrow, and adrenals
105
What organs are affected in transcoelomic seeding?
peritoneal, pleural, and pericardial and subarachnoid spaces
106
Grading is the appearance (microscopically/anatomically) while staging is (microscopic/anatomic)
grade: microscopic
stage: anatomic
107
What are the four levels of grading>?
well, moderately, poorly differentiated and undifferentiated
108
What are the four steps involved in invasion?
1. cell becomes less cohesive
2. attachment to matrix components
3. degradation of ECM
4. migration
109
reduction in E-cadherins facilitates what part of invasion?
cell becoming less cohesive
110
laminin and fibronectin are important proteins that invading cells bind in the (blank)
ECM
111
Collagenases and plasmin are (blank)proteinases used to break down the ECM
metalloproteinases
112
What two factors allow for migration of the invading cells?
cytokines and ECM cleavage products
113
When in the vasculature, tumor cells can form (blank) with leukocytes and platelets
emboli
114
What determines cancer tissue tropism once it gets into the blood?
1. vascular/lymphatic drainage
2. tumor adhesion molecules
3. microenvironment, eg proteases that inhibit binding
115
What does tissue tropism allow us to determine about cancer?
Can help figure out what the primary lesion was when you have a met of unknown origin
116
Tissue tropism of cancer is also known was what fancy name?
Soil Seed Hypothesis of Paget
117
T/F: Systemic met. is an early event
true
118
What clinical importance to CTCs have?
you can draw blood and test the cancer for biomarkers, chemo sensitivity and all kinds of shit
119
t/f: oncogenes and suppressor genes are involved in mets. and invasion
false; they are only involved in growth disregulation
120
T/F: a DTC is a met by definition
true; but a met is an actual grown tumor, a DTC is a single cell that may or may not become a tumore
121
Cancer (blank) cells allows for cancers to repopulate even after a full response to surgery and chemo
cancer stem cells
122
what percent of cancer cells are cancer stem cells?
0.1%
123
Self-renewal, symmetrical and assymmetrical division and pluripotency are all properties of all (blank) cells
stem cells
124
T/F: cancer stem cells are in a dormant state during active cancer
true; only involved in relapse or initial growth
125
Cancer stem cells experess what type of stem cell pathway?
embryonic stem cell
126
```
Hedgehog
Notch
Bmi-1
Wnt
Pten
These are all pathways and proteins involved in what process?
```
stem cell self-renewal; they are also found in the developing fetus!
127
Cancer cells tend to be CD44 (+/-) and CD24 (+/-)
CD44 pos and CD24 neg
128
CSC with full malignant potential will lead to mets in what time period?
months to years
129
CSC with partial malignant potential will show a period of (blank) followed by mets after many years
dormancy
130
What happens during the dormancy period of partially malignant CSCs that reactivate them?
secondary hits or changes in the microenvironment
131
Tumor (blank)may be a reflection of destroying the proliferating population of the tumor
regression
132
Tumor (blank) may be a reflection of the resistant stem cell fraction repopulating the tumor.
recurrence
133
T/F: tumor remission and response rates correlate with overall survival
false. :(
134
T/F: any gene or gene product made by cancer is a potential biomarker
true, but they must be ALTERED so they are unique
135
T/F: source of tumor biomarkers can be tissue, cytology, fluid, or serum
true
136
Small cell lung cancer, SIADH, Eaton-Lambert Syndrome, cerebellar ataxia are all types of (blank) syndromes
paraneoplastic
137
Cushing's syndrome involves the release of what hormone?
ACTH
138
small cell CA of the lung, pancreatic CA, and neural tumors that release ACTH are involved in what syndrome?
Cushing's
139
venous thrombosis involved in pancreatic and lung cancer is (blank) phenomena
Trousseu's
140
hypercalcemia associated with breast, renal, and squamous CA involves what hormone and cytokine?
PTHrP, TGFa
141
what type of cancer presents with hypertrophic osteoarthropathy and clubbing of the fingers?
CA of the lung
142
An increased met. rate despite reduced calorie intake leads to what state?
cachexia
143
What cytokine is involved in cachexia?
TNFa
144
PSA, CEA, and a-fetoprotein are all (blank) markers
tumor
145
T/F: tumor markers definitively diagnose the type of cancer
false; used for staging, detecting recurrences and monitoring effectiveness of therapy
146
What type of marker gives us info about prognosis, disease-FREE survival, overall survival, and length of latency?
Prognostic markers
147
What is Ki-67?
index of cell turnover, used to indicate cancers that divide rapidly
148
ER, Ki-67, p21 and p27 in prostate cancer, p53 in bladder cancer, and microsatellite gene instability products in colon cancer are what types of markers?
prognostic markers
149
What do surrogate end point markers tell us?
tell us the effectiveness of a Tx strategy before direct tumoral assessments can be made
150
When are surrogate end point markers most important?
during clinical trials
151
mTOR pathway in Head/Neck CA and FvG-Actin in bladder CA are (prognostic/SEMs)
SEMs
152
T/F: the prognostic biomarker is just as important as the drug
true
153
T/F: A survival benefit will not be seen in a randomized trial if benefit is restricted to 10-15% of the study population.
true
154
Clinically significant separation of Kaplan Meier curves in a randomized trial requires an effect in at least (blank) % of patients.
30-50
155
t/f: patient selection is not important in determining the effectiveness of a chemotherapeutic
false
156
```
cDNA microarrays
Proteomics
Array CGH
Sequencing
Tissue microarrays (TMAs)
are all high throughput approaches to developing (blank)
```
tumor biomarkers
157
BETTER SCREENING, CHEMOPREVENTION AND TARGETED THERAPY WILL ALL BE PREDICATED ON BETTER (blank)
tumor biomarkers
