Cancer Chemotherapy - Duan

Question 1

Is cancer self or foreign?

Answer 1

self

Question 2

what are the factors that promote cell proliferation in cancer?

Answer 2

shorter (accelerated) cell cycle
excessive proliferation
higher activity of nucleic acid and protein synthesis
altered cell-cell communication
invasive (disrupt normal healthy tissues)
migration to distant sites - metastasis

Question 3

T/F: cancer cells use the same metabolic processes and nutrients as host cells

Answer 3

true

Question 4

Growth Factor G-protein CR is involved in what part of the cell cycle?

Answer 4

G0 resting

Question 5

What is the MOA of Mitomycin C?

Answer 5

cross-links DNA; bifunctional alkylate

Question 6

When in the cell cycle does Mitomycin work?

Answer 6

G1

Question 7

Cytosine arabinoside, hydroxyurea, 6-MP, MTX, 5-FU all have what MOA and are therefore used in what part of the cell cycle?

Answer 7

block DNA synth, S phase

Question 8

Etoposide has what MOA and is effective in what part of the cell cycle?

Answer 8

inhibits topoisomerase II based DNA degradation and works in the G2 phase

Question 9

Vincristine, vinblastine, and taxanes block mitotic (blank) formation and therefore are active during what part of the cell cycle?

Answer 9

block mitotic spindle formation and are active during Mitosis

Question 10

Mechlorethamine, cyclophosphamide, and Ifosfamide are all (blank) mustards

Answer 10

nitrogen mustards

Question 11

Carmustine, lomustine, and streptozotocin are all what type of agent?

Answer 11

Nitrosoureas

Question 12

T/F: nitrosoureas interact with DNA specifically

Answer 12

false

Question 13

T/f: alkylating agents are active even during G0

Answer 13

true

Question 14

(blank) agents impair cell function by forming covalent bonds with the (blank) groups in biologically important molecules

Answer 14

amino, carboxyl, sulfhydryl, and phosphate

Question 15

Which nitrogen in guanine in DNA is most susceptible to alkylation?

Answer 15

N7 of guanine

Question 16

what was the first chemotherapy agent used in humans?

Answer 16

nitrogen mustards

Question 17

What is the main source of toxicity from nitrogen mustards?

Answer 17

DNA cross linkage

Question 18

The (blank) side chain in nitrogen mustards undergo an intramolecular cyclization to form carbonium ions intermediates

Answer 18

chloroethyl side chain

Question 19

The aziridine ring of nitrogen mustards attacks the (blank) of DNA base or protein, (blank) of DNA or phosphate, or the (blank) of protein

Answer 19

N of DNA base or protein, =O of DNA or phosphate, and -SH of protein

Question 20

Alkylation of the the 7 N in guanine in DNA makes it more (acidic/basic) causing it to mispair with what base?

Answer 20

acidic, thymine

Question 21

Nitrogen mustards cause a base pair substitution of?

Answer 21

A-T for GC

Question 22

Nitrogen mustards can open the imidazole ring or depurination by (blank) of the alkylated guanine residue

Answer 22

excision

Question 23

The 2nd chloroethyl side chain in bifunctional alkylating agents can alkylate a second guanine and cause (blanking) of two nucleic acid side chains

Answer 23

cross-links

Question 24

T/F: Cross-linking can happen both between and within strands

Answer 24

true

Question 25

Chlorambucil and melphalan work to form crosslinking (between/within) strands

Answer 25

between

Question 26

Cis-platinum cross links (between/within) strands

Answer 26

within

Question 27

(Between/within) strand cross linking has a high correlation with cytotoxicity

Answer 27

between

Question 28

What are the three major classes of adverse reactions to nitrogen mustards?

Answer 28

1. teratogenic 2. immunosuppressive 3. carcinogenic

Question 29

What are the two types of cancers that nitrogen mustards were used for?

Answer 29

lymphomas and leukemias

Question 30

what is the most reactive nitrogen mustard?

Answer 30

mechlorethamine

Question 31

What are the drugs used to MOPP up Hodgkin's disease?

Answer 31

mechlorethamine + oncovin (Vincristine) + | procarbazine + prednisone

Question 32

Since mechlorethamine is toxic to proliferating cells, the three major side effects include:

Answer 32

bone marrow suppression infertility GI toxicity (via IV)

Question 33

(blank) is more commonly known as Cytoxan or Neosar

Answer 33

cyclophosphamide

Question 34

What are the two methods of admin of Cytoxan?

Answer 34

oral or IV

Question 35

What is the 2 step MOA of Cytoxan?

Answer 35

1. bioactivation of prodrug via P450 | 2. DNA cross link of guanine N7

Question 36

What are the clinical uses for Cytoxan?

Answer 36

``` Never Neglect ALL BaCoN Nephrotic syndrome Non-hodgkin's lymphoma Acute lymphoid leukemia Breast cancer Carcinoid Neuroblastoma ```

Question 37

What are the B.A.D. side effects of Cytoxan?

Answer 37

Bone marrow suppresion Alopecia Disturbed GI hemorrhagic cystitis

Question 38

The CHOP regimen is used to treat what cancer?

Answer 38

Non-hodgkin's lymphoma

Question 39

Which nitrogen mustard is activated in the liver by ring hydroxylation?

Answer 39

Ifosfamide (Ifex)

Question 40

Ifex is used to treat (carcinoma/sarcoma) along iwth germ cell testicular cancer, cervical, lung, bone, ovarian, and breast

Answer 40

sarcoma

Question 41

Why do we give ifosfamide in conjunction with Mesna?

Answer 41

to reduce the urinary toxicity

Question 42

what added serious side effect does ifosfamide carry compared to cylcophosphamide?

Answer 42

increased platelet suppresion and urothelial damage

Question 43

Nitrosoureas form 2-chloroethyl carboniums that have what three MOAs?

Answer 43

1. crosslink DNA strands 2. break DNA strands 3. carbaboylate proteins

Question 44

What are the scary SE of nitrosoureas?

Answer 44

``` HIGHLY CARCINOGENIC profound and cumulative myelosuppresion renal failure alopecia hepatotoxicity pulmonary toxicity ```