Biochemistry 07 - Molecular Biology Of Cancer

Front 1

Define: benign tumors

Back 1

Grow slowly and are self-containing

Front 2

Define: malignant tumors

Back 2

Grows rapidly and are invasive

Front 3

Define: metastasis

Back 3

Occurs when tumor cells leave the site of initial tumor and form secondary tumors

Front 4

Define: angiogenesis

Back 4

Process of small tumor vascularizing in order to allow it to grow larger and maintain a blood supply

Front 5

How do u get cancer?

Back 5

Mutation in multiple genes which lead to malignant transformation of normal somatic cells(cancer = ↑ mitotic rate, de-differentiation, anaplasia (disordered growth pattern), not inhibited by cell-cell contact)

Front 6

What is the pathological pathway of cancer?

Back 6

Normal -> DYSPLASIA -> carcinoma in situ -> malignant carcinoma

Front 7

What are the causes of cancer?

Back 7

Inherited DNA mutation -> exposure to chemical carcinogens -> exposure to UV light -> viruses

Front 8

MOA of cancer -

Back 8

Dimethylnitrosamine -> oxidation in liver -> activated methyl group transferred to guanine -> during replication methylguanine base-pairs w/thiamine -> mutation into subsequent generations

Front 9

Define: adenocarcinoma

Back 9

Glandular tissue cancer

Front 10

Define: blastoma

Back 10

Embryonic tissue of organs cancer

Front 11

Define:carcinoma

Back 11

Epithelial tissue cancer

Front 12

Define: leukemia

Back 12

Tissues that form blood cells cancer

Front 13

Define: lymphoma

Back 13

Lymphatic tissue cancer

Front 14

Define: myeloma

Back 14

Bone marrow cancer

Front 15

Define: sarcoma

Back 15

Connective or supportive tissue cancer

Front 16

Pt w/ reciprocal translocation between chromoseom 9 + 22?

Back 16

Chronic myelogenous leukemia -> causes philadelphia chromosome

Front 17

What is wrong w/aneuploidy seen on karyotype?

Back 17

Tumor cell

Front 18

Game function mutation

Back 18

Gene becomes more active or more protein is produced

Front 19

What are proto-oncogenes?

Back 19

Regulate cell cycle, differentiation, gene expression, cell signaling pathways

Front 20

What is oncogenic transformation

Back 20

Occurs when normal cells start expressing an oncogene instead of proto-oncogene -> ↑ rate of cellular growth, growth at unusual sites, unregulated cellular proliferation

Front 21

What causes the conversion of proto-oncogenese -> oncogenes?

Back 21

Radiation -> mutation in promoter region -> excessive expression, gene rearrangement -> new promoter is spliced into place, gene amplification -> expression of multiple copies of proto-oncogeneses

Front 22

What are the growth factor signaling pathway components that are proto-oncogenes?

Back 22

1. Growth factors, 2. cell surface receptors, 3. monomeric G-proteins, 4. intracellular receptors, 5. intracellular tranduces, 6. trascription factors

Front 23

What is the cause of burkitts lymphoma?

Back 23

Caused by TRANSLOCATION of an ongogene; chromosome 8:14 rearrangement -> c-myc gene place under control of promotor for immunoglobulin heavy chain gene -> causes cellular growth in WBC

Front 24

How do u get chronic myelogenous leukemia(CML)?

Back 24

Caused by oncogenic transforamtion from a TRANSLOCATION 9:22 ->Bcr-abl fusion protein made -> Abl is a tyrosine kinase that is now always active

Front 25

Abl

Back 25

Chronic myelogenous leukemia - fused to Bcr -> tyrosine kinase activated - 9:22(gain-of-function)

Front 26

c-Myc

Back 26

Burkitts lymphoma - WBC growth - 8:14(gain-of-function)

Front 27

P53

Back 27

Cell cycle regulation -> p21 (loss-of-function)

Front 28

Ras

Back 28

GAPS (GTPase-activating proteins) ->MAP kinase(gain-of function)

Front 29

Rb1

Back 29

Binds E2F1 (loss-of-function)

Front 30

What is the cancer gene in signal transduction G-protein?

Back 30

Ras

Front 31

What is the cancer gene in tyrosine kinase (breast cancer)

Back 31

Src

Front 32

What is the cancer gene in transcription factors?

Back 32

Myc, fos, jun(breast cancer)

Front 33

What happens in a cell w/mutated RAS?

Back 33

Cell proliferates even w/o growth factor present

Front 34

What cascade does Ras activate?

Back 34

MAP kinase cascade

Front 35

Define: oncogenes

Back 35

Gain-of-function = Mutationally-activated form of a growth-promoting gene(normal = proto-oncogene)

Front 36

Define: tumor suppressor genes

Back 36

Loss-of-function = Normal genes that encode growth-inhibiting products that become inactivated in cancer cells

Front 37

What are the tumor suppressor proteins?

Back 37

Rb + p53 - prevents gene transcription from occurring by binding directly to DNA or binding to transcriptional activators

Front 38

What is the MOA of BRCA1+ BRCA2 genes?

Back 38

BRCA genes = repair of double strand DNA breaks -> loss of BRCA results in loss of DNA repair capabilities -> cancer(loss-of-function)

Front 39

What are the important tumor suppressor?

Back 39

1. Rb, 2. p53, 3. BRCA

Front 40

Deletion in Rb?

Back 40

Retinoblastoma -> mutation in children = cancer in the eye; normally Rb binds and inactivates E2F1 (normal function = initiates G1/S cell cycle transition) -> thus Rb deletion allows activation of E2F1 -> cell cycle progresses

Front 41

P53 deletion

Back 41

P53 normally checks DNA viability -> apoptosis; p53 deletion -> allows cell to progress thru cell cycle

Front 42

Li-Fraumeni syndrome

Back 42

Inherited mutation in a p53 allele -> thus u are heterozygous -> 25x ↑ in chance of getting cancer -> cancer by 30 yo

Front 43

What initiates apoptosis?

Back 43

Cytochrome C -> TNF ->caspases -> apoptosis

Front 44

What inactivates caspases?

Back 44

Prosacpases; they are activated by apoptosome (cytochrome C + Apaf-1) -> procaspases -> caspase

Front 45

What are the ways to treat cancer?

Back 45

1. Anti-folates(methotrexate), 2. base analogues(5-Fu), 3. alkylating agenst(cyclophosphamide), 4. ionizing radiation(only used in cancer where p53 is still intact)

Front 46

Cancer treatment that interferes w/mitoic aparatus

Back 46

1. Microtubule depolymerizing drugs(vinblastine), 2. microtubule polymerizing drugs (taxol)

Front 47

Cancer treatment that chokes off blood supply

Back 47

Avastin - blocks VEGF (blocks angiogenesis soluble growth factor)

Front 48

What is the treatment of cancer using inhibitors?

Back 48

Herceptin -> monoclonal antibody that blocks Her 2 protein in breast cancer, 2. gleevec(imatinib) -> active site inhibitor -> binds to active site of Bcr-abl tyrosine kinase in chronic myelogenous leukemia