Cancer and Carcinogens Flashcards
(93 cards)
1
Q
What re the 3 stages of neoplastic development? How does it progress from each stage to the next?
A
- Neoplastic cell (growth/promotion) - Differentiated neoplastic cell (progression) - Undifferentiated cancer
2
Q
What are the 4 properties of chemical carcinogens?
A
- Carcinogenesis is dose dependent
- Long lag periods between exposure and appearance of tumors (> 20 years in humans)
- Carcinogens are subject to activation and degradation
- Active carcinogens are electrophiles
3
Q
What is an active carcinogen called?
A
Pro-carcinogens
4
Q
What were the findings of the Mega Mouse experiment?
A
- Mice were given a carcinogen at very low levels
- Kidney cancer developed linearly
- Bladder cancer had no response
- Some cancers respond linearly to carcinogen exposure
- Some do not develop at all at low levels
5
Q
How many different well established human chemical carcinogens have been discovered?
A
More than 20
6
Q
What are 9 examples of human chemical carcingens?
A
- Aflatoxins
- Benzopyrene
- Benzene
- Conjugated estrogens
- Cyclophosphamide
- Mechlorethylamine
- Phenacetin
- TCDD
- Vinyl chloride
7
Q
What carcinogen develops in moldy food stuffs?
A
Aflatoxins
8
Q
What carcinogen is a nitrogen mustard/ nerve gas?
A
Mechlorethylamine
9
Q
What human chemical carcinogen is the most potent?
A
Aflatoxins
10
Q
What human chemical carcinogen is a product of combustion?
A
Benzopyrene
11
Q
What human chemical carcinogen is an immunosuppressant?
A
Benzene
12
Q
What 2 human chemical carcinogens are alkylating agents?
A
- Cyclophosphamide
- Mechlorethylamine
13
Q
What human carcinogen results from DES exposure?
A
Cyclophosphamide
14
Q
What human chemical carcinogen is a coal tar derivative?
A
Phenacetin
15
Q
What human carcinogen is used to make PVC plastic?
A
Vinyl chloride
16
Q
What human carcinogen is dioxin?
A
TCDD
17
Q
How do direct acting carcinogens work?
A
Mechlorethylamide or another electrophile attach to reactive sites on DNA, altering genes
18
Q
What activates carcinogens into procarcinogens?
A
Cytochrome P450
19
Q
What are 3 types of epigenic carcinogens?
A
- Immunosuppresors (Benzene)
- Hormones (DES)
- Solid-state carcinogens (Asbestos)
20
Q
What are oncogenes?
A
Genes taht encode for transforming proteins that can cause cancer
21
Q
What do oncogenes develop from?
A
Proto-oncogenes (genes in normal cells that encode for proteins involved in cellular regulation)
22
Q
What are proteins involved in cell regulation?
A
- G proteins
- Tyrosine-specific kinases
- Other protein kinases
- Growth factors
- Transcription regulators
23
Q
What are anti-oncogenes?
A
Tumor suppressor genes
24
Q
What stages of cell point do cells normally go through “checkpoints?
A
- G1
- G2
- Metaphase
25
What are the oncogenes involved in breast cancer?
- BRCA1
| - BRCA2
26
What are 5 childhood tumors with high cure rates? What do they have in common?
- Acute lymphocytic leukemia
- Burkitt's lymphoma
- Ewing's sarcoma - bone tumor
- Retinoblastoma
- Wilms' tumor - kidney tumor
All fast growing
27
What are 5 adult tumors with high cure rates?
- Hodgkin's disease
- Non-Hodgkin's lymphomas
- Trophovlastic choriocarcinoma
- Testicular germ cell cancer
- Ovarian germ cell cancer
28
How does chemotherapy work?
- Inhibits cell proliferation
| - Cancer cells are rapidly proliferating, and are especially sensitive
29
What non-cancer cells are affected by chemo?
- Bone marrow
- Hair
- GI
- Oral mucosa
- Other rapidly dividing cells
30
What drug is used to increase WBCs in combination with chemo?
- Filgrastim (Neupogen)
31
Why do patients often experience nausea during chemotherapy?
- Chemical trigger zone is one of only areas without blood brain barrier, and is sensitive to the drug
32
What drug can be used to prevent the nausea associated with chemo?
Ondansetron (Zofran)
33
What causes resistance to chemotherapy?
Cancer cells divide fast, and adapt to the drugs. The most common mechanism is P-glycoprotein that pumps the toxins of the chemotherapy out of the tumor
34
How can multiple agents be used in chemotherapy?
Use drugs that different different parts of the cell cycle
35
What is the ABVD regimine therapy for Lymphoma-Hodgkin's?
- Doxorubicin
- Bleomycin
- Vinblastine
- Dacarbazine
36
What type of drugs generally work in the DNA synthesis portion of the cell cycle?
Anti-metabolites
37
What is growth fraction?
Proportion of cells actively profliterating
38
What are the grow characteristics of tumors?
- Grows rapidly initially
| - Slows because it can't support its own growth due to hypoxia, poor nutrient supply, immunological defenses
39
What is the log kill hypothesis?
Chemotherapy reduces the tumors to a level at which the body's immunological responses can take over and completely eliminate the cancer
40
What is the MOA of alkylating agents?
- Transfer alkyl groups to DNA, inhibiting cell division
41
What portion of the cell cycle do alkylating agents affect?
Non-specific
42
What are 3 adverse effects of alkylating agents?
- Bone marrow suppression
- Nausea
- Vomiting
43
Why must alkylating agents be administered via IV?
They have vesicant properties, meaning outside of the blood vessel, it can cause tissue damage and necrosis
44
What are 2 examples of alkylating agents?
- Mechlorethamine (mustargen)
| - Ifosfamide (lfex)
45
Why can Ifosfamide be taken orally even though it is an alkylating agent?
It is activated by the body
46
What is the MOA of platinum coordination compounds?
Similar to alkylating agents
| - Use meta complexes
47
What are 2 examples of platinum coordination compounds? What do they target?
- Cisplatin (testies, lymph tissue, ovaries)
| - Carboplatin (paraplatin) (ovarian cancers)
48
What is an adverse effect of platinum coordination compounds?
Kidney toxicity
49
What is the MOA of antimetabolites?
Inhibit metabolic steps required for DNA synthesis
50
What phase of the cell cycle do antimetabolites act on?
S phase
51
What are 5 adverse effects of antimetabolites?
- Immunosuppresant
- GI lesions
- Alopecia
- Bone marrow depression
- Skin rash
52
What other conditions may antimetabolites be used to treat?
Autoimmune diseases such as RA
53
What antimetabolite targets folic acid?
Methotrexate
54
What antimetabolite targets purine synthesis?
Mercaptopurine
55
What antimetabolite targets pyrimidine synthesis?
Fluorouracil
56
What plant are vinca alkaloids derived from?
Periwinkle plant
57
What phase of the cell cycle do vinca alkaloids act on?
M phase
58
What types of cancer are vinca alkaloids use din?
- Breast cancer
| - Choriocarcinoma
59
What are 4 adverse effects of vinca alkaloids?
- Bone marrow suppresion
- Alopecia
- GI lesions
- Neurotoxicity
60
What are 2 vinca alkaloids?
- Vincristine
| - Vinblastine
61
What is the MOA of cytotoxic antibiotics and synthetics?
- Bind to DNA to inhibit RNA synthesis
62
What cell phase do cytotoxic antibiotics and synthetics act on?
G2 phase
63
What are adverse effects of cytotoxic antibiotics and synthetics?
- Visual toxicity
| - Unique, drug-specific side effects
64
What antibiotic/ synthetic drug is used to treat lung fibrosis?
Bleomycin
65
What is an example of anti-estrogen drug? What is it used for?
- Tamoxifen
| - Treats breast cancer
66
What are other TYPES of hormonal drug therapies?
- Androgens for breast cancer
- Anti-androgens for prostatic cancer
- Progestins for advanced breast cancer or endometrial carcinomas
67
What drugs block cancer cell signaling?
- Tyrosine Kinase Inhibitors
- Monoclonal Antibodies
- Cox-2 inhibitors
- Thalidomide
68
What signals do Tyrosine Kinase Receptors transduce?
- Growth
- Division
- Migration
- Synthesis
- Apotosis
69
What type of protein are Tyrosine Kinases?
An enzyme
70
What does Tyrosine Kinase act on? What do they do?
Phosphorylates tyrosine residues
71
What cells do tyrosine kinase receptors become active in?
Cancer cells
72
What are some major TKR families?
- Epidermal growth factor receptor & family
- Vascular endothelial growth factor receptor & family
- Insulin receptor and family
- etc...
73
What types of cancer demonstrate high epidermal growth factor receptor expression?
- NSCLC
- Prostate
- Gastric
- Breast
- Colorectal
- Pancreatic
- Ovarian
74
What is high expression of EGFR associated with?
- Invasion
- Metastasis
- Late-stage disease
- Chemotherapy resistance
- Hormone-therapy resistance
- Poor outcome
75
What is VEGFR increased in patients with growing tumors?
Large tumors require blood vessels to grow instead of relying on diffusion from nearby blood vessels.
- Tumors release VEGF to stimulate growth of new vessels into the tumor
76
How large can a tumor grow without a blood supply?
1 - 2 mm^3
77
What is angiogenesis?
Growth of new blood vessels
78
Do tyrosine kinase inhibitors act inside or outside of the cell?
Inside
79
What is a tyrosine kinase inhibitor that is specific to Bcr-Ab which is active in CMLl?
Gleevec
80
What organ does tyrosine kinase inhibitors adversely affect?
Skin
81
What is CML?
Chromosomal rearrangement that fuses two genes together.
| - Produces oncogene, which encodes a form of tyrosine kinase (BCR-ABL)
82
What type of TKR inhibitor can act outside of the cell?
Monoclonal antibodies
83
What monoclonal antibody targets breast cancer?
Herceptin (Trastuzumab)
84
What monoclonal antibody is the only one that targets blood vessels?
Avastin (Bevacizumab)
85
What type of cancer is Avastin used to treat?
- Colorectal carcinoma
86
What are 3 adverse effects of Herceptin?
- Cardiomyopathy
- Anemia/ leukopenia
- Rashes
87
What are 4 adverse effects of Avastin?
- Thrombosis
- Hypertension
- Proteinuria
- Bleeding
88
How does Cox-2 facilitate tumor development?
Cancer cells overexpress Cox-2, causing an expression of VEGF through production of PGE2
89
How is Cox-2 treated?
- Cox-2 inhibitors downregulate angiogenesis causing factors such as VEGF
90
What does Thalidomide block angiogensis?
- Blocks VEGF through a decrease in the cell's ability to induce COX2 expression
91
What type of cancer is Thalidomide best suited towards treated?
Multiple Myeloma (plasma cell disorder)
92
What is the limitation of antiangiogenic therapy when compared with other chemotherapies?
- Inhibits tumor growth instead of regressing established tumors
93
What is the clinical value of antiangiogenic therapy?
- Prolongs acute conditions to chronic
| - Gives individuals extra time (extra month)
