Neoplasia 4 Factors Leading to Cancer/Carcinogenic agents

Question 1

chromosomal changes

Answer 1

Question 2

chromosomal translocations

chromosomal rearrangement that activate proto-oncogenes? in what 2 ways?

ex disease? what is rearranged?

how does a translocation occur?

CML?

Answer 2

Question 3

acute promyelocytic leukemia?

Answer 3

An exception with important clinical consequences is found in a form of leukemia called acute promyelocytic leukemia (APML). APML is virtually always associated with a reciprocal translocation between chromosomes 15 and 17 that produces a PML-RARA fusion gene (Fig. 7-41). How this fusion gene functions is now reasonably well understood.

• The fusion gene encodes a chimeric protein consisting of part of a protein called PML and part of the retinoic acid receptor-α (RARα). Normal RARα binds to DNA and activates transcription in the presence of retinoids. Among the RARα responsive genes are a number that are needed for the differentiation of myeloid progenitors into neutrophils.
• The PML-RARα oncoprotein has diminished affinity for retinoids, such that at physiologic levels retinoids do not bind to PML-RARα to any significant degree. In this “unliganded” state, it retains the capacity to bind DNA, but instead of activating transcription, it inhibits transcription through recruitment of transcriptional repressors. This interferes with the expression of genes that are needed for differentiation, leading to a “pile-up” of proliferating myeloid progenitors that replace normal bone marrow elements.
• When given in pharmacologic doses, all-trans retinoic acid binds to PML-RARα and causes a conformational change that results in the displacement of repressor complexes and the recruitment of different complexes hat activate transcription. This exchange overcomes the block in gene expression, causing the neoplastic myeloid progenitors to differentiate into neutrophils and die, clearing the marrow over several days and allowing for recovery of normal hematopoiesis. This highly effective therapy is the first example of differentiation therapy, in which immortal tumor cells are induced to differentiate into their mature progeny, which have limited life spans. It has also spurred efforts to develop drugs that target other nuclear oncoproteins, despite the inherent difficulty of the problem.

Question 4

Deletions

associated with loss of?

Answer 4

Question 5

gene amplification

leads to? result from? two mutually exclusive patterns seen?

2 important ex of amplifications?

Answer 5

Question 6

chromothrypsis

what is it?

key concepts of genetic lesions in cancer?

Answer 6

Question 7

epigenetic changes

important role in?

Answer 7

Question 8

epigenetic alterations in cancers? 3

Answer 8

Question 9

epigenetic.

what has an epigenetic basis?

therapeutic target why?

cancer exhibit what epigenetics?

Answer 9

Question 10

noncoding RNAs and cancer

what is a miRNA? in cancer?

whats an onco-mIRs? important for? incancer

tumor suprresive miRs in what specific cancers?

tumor suppressive properties of mIR processing factors? important protein?

other noncoding RNAs?

Answer 10

Question 11

molecular basis of multistep carcinogenesis

how do cancers get all of their hallmarks?

how many?

in experiment what ar ethe 5 mutations needed? (epithelial cells)

steps precancerous v?s adenocarcinomas

Answer 11

Question 12

steps of mutations in colorectal cancer through adenoma-carcinoma sequence

Answer 12

Question 13

steps in chemical carcinogenesis

3

i- results from? what happens

above causes what damage? this causes?

p- do what?

what if promoting agent comes first?

carcinogens are what type of molecule? targets are?

initiation types?

Answer 13

Question 14

experimental data of initiators and promoters that will and wont cause tumors

Answer 14

Question 15

Direct acting carcinogens

what are they?

strength? some important because they are? causes?

Answer 15

Question 16

indirect acting carcinogens

what are they? other name? strength? ex?

most chem carcinogens require what to turn?

most are metabolized by?

example of susceptibility of a P-450 gene? protein involved? at risk for? other influences?

Answer 16

Question 17

molecular targets of chem carcinogens.

cancer initiation how would this happen?

is there preference?

ex?

Answer 17

Question 18

promotion of chem carcinogenesis

promoters are chem agents that cause what?

initiator as promoter?

classically?

Answer 18

Question 19

Radiation carcinogenesis

what is it?

Answer 19

Question 20

UV rays

who more at risk? type of cancer?

nonmelanoma cancer associated with? melanomas?

which UV is shitty? why not the other one?

carcinogenicity of this light is due to? leads to? repaired by?

disease if that is faulty?

Answer 20

Question 21

ionizing radiation

what are these?

CT scans?

most likely cancers?

Answer 21

Question 22

oncogenic RNA virus

what type of virus? what does it cause? location?

major target cell? infection via?

what leads to opportunistic infections?

does the virus have oncogene? what gene alows transforming activity? allows what? what hallmarks gained?

Answer 22

Question 23

Oncogenic DNA viruses

what 5?

Answer 23

Question 24

HPV what are the high risk types? types of cancer?

HPV genes go where? this interrupts what? where? loss of this leads to overexpression of?

oncogenic potential largely explained by?

oncogenic activities of E6? E7?

Answer 24

Question 25

summarize high risk HPV do what?

need what else for carcinogenesis?

can HPV be cleared?

HPV and HIV?

Answer 25

Question 26

Epstein-Barr virus

most common associated tumor? infects what cells?

causes what to happen?

key step to EBV oncogenesis?

Answer 26

Question 27

EBV and what cenral africa/new guinea cancer? children

link? other factors involved? 3

Answer 27

In summary, in the case of Burkitt lymphoma, it seems that EBV is not directly oncogenic, but by acting as a polyclonal B-cell mitogen, it sets the stage for the acquisition of the (8;14) translocation and other mutations that ultimately produce a full-blown cancer

Question 28

EBV more direct role in what cancer? in what patients?

usually lack what translocation?

southern china/inuit? different cancer?

Answer 28

Question 29

Hep B/C

type of cancer?

what factors for HB/CV? the dominant effect?

immune response?

liver injury leads to? what blokcs apoptosis?

HBV gene?

HCV difference?

Answer 29

Question 30

H. pylori

cancers? how is in carcinogenic? pathway to cancer?

what helps with penetration?

cancer lymphoma origins?

what cure this cancer?

Answer 30

Question 31

local and hormonal effects

location effects? can be helpful?

endocrine effects? functional activity usually?

Answer 31

Question 32

cancer cachexia

associated with? 3

equal loss of? elevated? evidence of?

leading suspect in this process?

Answer 32

Question 33

Paraneoplastic syndromes

what are they? important to recognize because?

endocrinopathies are what? most common one? cancer involved?

most common paraneoplastic syndrome? so much so that? cancer associtaed hypercalcemia?

Answer 33

Question 34

paraneoplastic hypercalcemia of malignancy. humoral factor related? does what? tumors associated? acanthosis nigricans?

hypertorphic osteoarthropathy? associated with?

vascular hem manifestation?

Answer 34

Question 35

Grading cancer is based off of?

range from what categories?

Staging. what is it based off of?

what system used? what labels used?

Answer 35

Question 36