carcinogens Flashcards
(120 cards)
1
Q
What are the three stages for neoplastic development and progression?
A
Neoplastic cell
Differentiated neoplasm
Undifferentiated cancer
2
Q
Property of chemical carcinogens
Carcinogens are _________ dependent.
A
Dose dependent
3
Q
Property of chemical carcinogens
Is lag period for exposure and a tumor long or short.
A
Can be greater than 20 years
4
Q
Property of chemical carcinogens
Carcinogens are subject to what two processes?
A
Activation and degradation
5
Q
Property of chemical carcinogens
What are active carcinogens?
A
electrophiles
6
Q
Most potent carcinogen known?
A
aflatoxins
7
Q
Carcinogen that is a product of combustion?
A
Benzopyrene
8
Q
Carcinogen used to make PVC plastic
A
Vinyl chloride
9
Q
Carcinogen that is a coal tar derivative
A
Phenacetin
10
Q
Carcinogen that is an immunosuppressant
A
Benzene
11
Q
What type of estrogen is a carcinogen?
A
Conjugated estrogen
12
Q
2 carcinogen that are alkylating agents
A
amine/amide
Cylophosphamide
Meclorethylamine
13
Q
What are the 3 classes of carcinogens?
A
Direct acting carcinogen
Procarcinogen
Epigenic carcinogen
14
Q
Examples of direct acting carcinogens
A
Mechlorethlamine+guanine
Results in depurination an abnormal base pairing
15
Q
Examples of procarcinogens
A
Benzopyrene
Vinyl chloride
16
Q
Examples of epigenic carcinogens
A
Immunosuppressor (Benzene)
Hormones (DES)
17
Q
Gene that encodes for transforming proteins that cause cancer
A
Oncogenes
18
Q
Genes in normal cells that encode for proteins involved in cellular regulations
A
Proto-oncogenes
19
Q
Oncongens are derived from the mutation of what?
A
Proto-oncogenes
20
Q
What are G proteins, tyrosine-specific kinase, kinases, growth factors and transcription regulators
A
Proteins involved in cellular regulation
21
Q
What is an anti-oncogen? AKA?
A
Tumor suppressor gene
Growth suppressor genes
22
Q
What does an anti-oncogen do?
A
Suppresses cell growth
23
Q
what does the mutation of anti-oncogen lead to?
A
loss of ability to restrain cell growth and cell division…..the mutated anti-oncogen produces a mutant protein that is inactive as a growth suppressor
24
Q
what are these? Acute lymphocytic leukemia Burkitt's lymphoma Ewings' sarcoma - bone tumor Retinoblastoma Wilms' tumor - kidney tumor
A
childhood tumors with high cure rates
25
```
what are these?
Hodgkin's disease
Non-Hodgkin's lymphomas
Trophoblastic choriocarcinoma
Testicular and ovarian germ cell cancers
```
adult tumors with high cure rates
26
what is the mechanism through which chemotherapy drugs work?
inhibit cell proliferation
27
why are tumor cells sensitive to chemotherapy drugs?
they are rapidly proliferating
28
what healthy cells in the body are also affected by chemotherapy drugs and why?
```
bone marrow
hair
GI
oral mucosa
also rapidly proliferating
```
29
what is Filgrastim (Neupogen)?
granulocyte colony stumilating factor used to increase WBCs
30
common side effect of chemo?
nausea and vomiting
31
what are Compazine, Marinol, and Zofran?
drugs used in chemo to reduce nausea/vomiting
32
can resistance occur with cancer drugs?
yes
33
what causes resistance to cancer drugs and where are they located?
G-glycoprotein pumps that reside in the cell membranes
34
what are two ways that drug resistance is combated?
-use of multiple agents that work on different parts of the cell
-use different agents that have different toxicities
Together this is known as:
COMBINATION THERAPY
35
what is the "ABVD regimen" used to treat? how often is the cycle repeated?
Hodgkin's lymphoma
| every 28 days
36
```
what are these drugs:
doxorubicin
bleomycin
vinblastine
dacarbazine
```
the ABVD regimem for H. lymphoma
37
most anticancer drugs are what/do what 2 things?
cytotoxic
block cell proliferation
(send cell into G0 phase of mitosis)
38
what is the growth fraction?
proportion of cells actively proliferating
39
tumor growth rate is __________.
initially rapid (exponential)
40
why does tumor growth rate slow?
- decrease in growth fraction
| - cell loss due to hypoxia, poor nutrition supply, immunological defenses
41
how do alkylation agents work to treat cancer?
transfer alkyl groups to DNA which inhibits cell division
42
alkylating agents are cell-cycle _______.
non-specific
43
what are the adverse effects of alkylating agents?
bone marrow suppression
| N and V
44
some alkylating agents are potent _________.
vesicants
45
what is a vesicant?
causes blistering or skin reactions
46
what are Mustargen and Iflex?
alkylating agents
47
what is a platinum coordination compound?
a metal complex
48
how do platinum coordination compounds work?
similar to alkylating agents
| inhibits cell division
49
what type of drug in cisplatin and what is it used for?
platinum coordination compound
| neoplasm of testes, lymph tissues, ovaries
50
platinum coordination compounds are highly effective but limited by what?
nephrotoxicity
51
what is Paraplatin?
platinum coordination compound
| ovarian cancers
52
how do antimetabolites work?
inhibit metabolic steps needed for DNA synthesis
| sometimes used as an immunosuppressive
53
what types of DNA synthesis are inhibited by antimetabolites?
folic acid
purine
pyrimidine
54
methotrexate inhibits what?
folic acid synthesis
55
mercaptopurine inhibits what?
purine synthesis
56
fluorouracil inhibits what?
pyrimidine synthesis
57
during what phase of the cell cycle do antimetabolites work?
S phase
58
adverse effects of antimetabolites?
```
immunosuppressive
skin rash
bone marrow suppression
GI lesions
alopecia
```
59
how do vinca alkaloids work?
inhibit M-phase of mitosis in cell cycle
60
what are vinca alkaloids used to treat?
breast cancer
| choriocarcinoma
61
how are vinca alkaloids made?
from periwinkle plant
62
what are the adverse effects of vinca alkaloids?
bone marrow suppression
GI lesions
alopecia
neurotoxicity
63
what are vincristine and vinblastine
vinca alkaloids
64
how do cytotoxic antibiotics and synthetics work?
bind to DNA
| inhibit RNA synthesis (G2 growth phase)
65
what is bleomycin? what is its serious side effect?
```
cytotoxic antibiotic
lung fibrosis (impaired lung function)
```
66
what types of cancers are treated with hormones?3
breast
prostatic
endometrial carcinoma
67
fluoxymesterone and testalactone are examples of what type of hormone and are used to treat what?
androgens
| breast cancer
68
flutamide and bicalutmide are examples of what type of hormone and are used to treat what?
anti-androgens
| prostatic cancer
69
anti-androgen hormones used to treat prostatic cancer are often combined with what?
LHRH agonists (like Leuprolide)
70
what are progestin used to treat?
advanced breast cancer
| endometrial carcinoma
71
what is tamoxifen and what is it used for?
an anti-estrogen
| breast cancer
72
what do tyrosine kinase inhibitors, monoclonal antibodies, cox-2 inhibitors, and thalidomide have in common?
all block cancer cell signaling
73
tyrosine kinases receptors transduce signal that direct what 5 things in cells?
```
growth
division
migration
synthesis
apoptosis
```
74
what are tyrosine kinases?
enzymes that phosphorylate tyrosine residues
75
how does tyrosine kinases and signal transduction work?
1. ligand binds to 2 inactive receptors
2. the ligand brings the 2 receptors together (called receptor dimerization)
3. causes receptor autophosphorylation and activation to occur
76
7 major tyrosine kinases receptor families
```
Insulin Receptor and Family
Platelet-Derived GFR and F
Fibroblast Growth Factor Receptor & Family.
Hepatocyte GFR and F
Epidermal GFR and F
Vascular endothelial GFR and F
Ret Receptor (Orphan)
```
77
```
what is true of all of these tumors?
NSCLC (non-small cell lung cancer)
prostate
gastric
breast
colorectal
pancreatic
ovarian
```
these tumors show high epidermal growth factor receptor (EGFR) expression
78
high epidermal growth factor receptor (EGFR) expression is associated with what 6 things?
```
invasion
metastasis
late-stage
chemo resistance
hormone-therapy resistance
poor outcome
```
79
Angiopoietin-1 (Ang-1) activates what, leading to what?
the VEGF receptor and leads to vessel stability
80
angiopoietin-2 (Ang-2) binds to what, leading to what?
the VEGF receptor and competitively inhibits
| Ang-1, leading to vessel instability.
81
what is angiogenesis?
generation and growth of new blood vessels
82
how will an absence of blood supply affect tumor growth?
will limit tumor growth to 1-2mm (cubed)
83
what causes a tumor to secrete a growth factor and what effect does that have on blood vessels?
```
secrete growth factor in response to hypoxia
promotes angiogenesis (vessel growth)
```
84
what are VEGFs, EGF, FGFs, PDEGFs, and PIGF?
VEGF (Vascular endothelial growth factor)
EGF (Epidermal growth factor)
FGFs(Fibroblast growth factor, acidic or basic)
PDEGF (Platelet-derivate endothelial growth factor)
PIGF (placenta growth factor)
85
for colorectal cancer, the metastasis of the cancer correlates with what two things?
number of blood vessels
| VEGF levels
86
how do tumors measuring less than 1 mm receive O2 and nutrients?
diffusion from vasculature
87
large tumors require what (in relation to blood vessels)
new vessel network
88
what is the sequence of new blood vessel generation in regards to tumors?
1. tumor secretes angiogenic factors
2. angiogenic factors stimulate migration, proliferation, and blood vessel development in adjacent blood vessels
3. new blood vessels form and vascularize tumor
4. facilitation of tumor growth
89
TKR inhibitors (small molecules) work through what 5 strategies?
```
Inhibits:
proliferation and maturation of tumor
chemotherapy resistance
angiogenesis
metastasis
anti-apoptosis
```
90
what are Iressa, Tarceva, Gleevec?
Tyrosine Kinase Inhibitors
91
Iressa and Tarceva target what receptors?
Her-1
92
Gleevec targets what receptors?
Bcr-Abl (a Tyrosine kinase that is always active in CML)
93
Iressa (gefitinib) is used to treat what kinds of cancer? AKA?
Non-small cell lung cancer
| ZD1839
94
how is Iressa administered and in what dose?
orally
| 250=500 mg daily
95
Iressa adverse side effects? 4
Skin rash (72%)
Diarrhea (35%)
Nausea/vomiting
myelosuppression (i.e. bone marrow suppression)
96
what is Tarceva used to treat?
advanced or metastatic non-small cell lung cancer
being investigated for use in:
head and neck squamous cell carcinoma
advanced ovarian cancer
97
Tarceva adverse side effects? 1000
```
Cutaneous toxicity (72-88%)
Diarrhea
Nausea/vomiting
headache
fatigue
hyperbilirubinemia
myelosuppression
mucositis
```
98
what was Gleevec designed to treat?
CML (chronic myeloid leukemia)
99
what causes CML (chronic myeloid leukemia)?
a chromosomal rearrangement that fuses two genes together produces an oncogene that in turn produces an enzyme called BCR-ABL (type of tyrosine kinase)
BCR-ABL is always active and causes an overproliferation of WBCs
100
what is the hallmark of CML (chronic myeloid leukemia)?
overproliferation of WBCs
101
TKR inhibitors (monoclonal antibodies) work through what 5 strategies?
```
same as small molecules
Inhibits:
proliferation and maturation of tumor
chemotherapy resistance
angiogenesis
metastasis
anti-apoptosis
```
102
Herceptin, Erbitux, and Avastin are all example of what?
monoclonal antibodies
103
Read this:
Fully humanized IgG monoclonal AB has been generated using XenoMouse technology, in which human immunoglobulin genes were introduced into mice engineered to lack functional mouse immunoglobulin genes. The full humanization would be expected to result in no immunogenicity and a slower clearance rate of the mAB, compared with mouse or mouse-derived mAbs, thus allowing repeated antibody administration in immunocompetent patients.
Read this:
Fully humanized IgG monoclonal AB has been generated using XenoMouse technology, in which human immunoglobulin genes were introduced into mice engineered to lack functional mouse immunoglobulin genes. The full humanization would be expected to result in no immunogenicity and a slower clearance rate of the mAB, compared with mouse or mouse-derived mAbs, thus allowing repeated antibody administration in immunocompetent patients.
104
skin reactions to monoclonal antibodies are related to what?
prominent roles of erbB1 and EGF-like ligands in epidermal tissues
105
Herceptin is FDA approved to treat what?
HER2 positive metastatic breast cancer
106
adverse side effects of Herceptin?
Cardiomyopathy
Anemia/leukopenia
Rashes
107
Erbitux is FDA approved to treat what? combined with what?
metastatic colorectal cancer
| mono or irinotecan combination
108
adverse side effects of Erbitux?
Acneiform rash
| follicullitis (80% cases)
109
Avastinis FDA approved to treat what? combined with what?
colorectal carcinoma
| used in combination with 5FU
110
Humanized MoAB may have what adverse effects?
Infusion associated symptoms, hypersensitivity reactions, including fatal anaphylaxis.
111
Do fully humanized MoAB have immunogenesity reactions?
no
112
how do cox-2 inhibitors and angiogenesis work?
Cox-2 inhibitors indirectly downregulate the activity of angioneogenic factors such as VEGF
113
cox-2 inhibitors induce expression of what? how?
VEGF
| through the production of PGE2
114
cancer cells ______ Cox-2
overexpress
115
how does thalidomide work?
Thalidomide inhibits angiogenesis by blocking VEGF which decreases the cells' ability to induce Cox2 expression
116
how does thalidomide affect an unborn fetus?
reduces angiogenesis in limbs causes deformation
117
most of the data collected on thalidomide concerns what types of disorders?
plasma cell disorders (specifically refractory relapse multiple myeloma)
118
what does antiangiogentic therapy do?
leads to inhibition of tumor growth rather than regression of established tumors
119
Antiangiogenic therapy has the potential to do what?
convert an acute disease to a chronic disease (does not cause regression)
-this may extend a patients life more than traditional therapy because traditional therapy may completely fail and lead to death, while a person may be able live a long time with a tumor that is not growing
120
Current anticancer therapy may cause what two things to happen?
either cause tumor regression or slow the progress of the tumor growth until failure of therapy
