oncology

Question 1

benign vs malignant tumpr

Answer 1

benign remains localized, malignant is locally invasive or metastatic (spread by lymph or blood to other parts of the body.

Question 2

carcinoma

Answer 2

tumor of epithelial origin

Question 3

sarcoma

Answer 3

tumor from fibroblast

Question 4

lymphoma and leukemia

Answer 4

lymphoma is solid and leukemia is circulating cells, both from leukocyte origin (white blood cells)

Question 5

proto-oncogenes

Answer 5

genes encoding proteins that gives go signal in checkpoint during cell cycle, also called c-onc. examples of these are growth factors, growth factor receptors, intracellular signal transducers and transcription factors.

Question 6

v-onc

Answer 6

viral gene that is a slighly modified version of a cellular oncogene

Question 7

EBV latent membrane protein 1

Answer 7

causes constitutive antiapoptosis (decreased activity of BCL-2), cell cycle progression (increased activity of CDks etc) and cell proliferation and survival

Question 8

tumor suppressing genes

Answer 8

encodes proteins involved in negative regulation of growth, stop signals. ex p53 and RB. p53 is targeted by many of these cancer inducing viruses.

Question 9

E1A from adenovirus

Answer 9

is capable of associating with many proteins, ex RB which is an important checkpoint protein and other cofactors involved in regulating phosphorylation of cyclin CDK complex

Question 10

E6 from papolloma virus

Answer 10

associates with p53 and cellular oncogenes like c-MYC

Question 11

retroviruses induction of cancer

Answer 11

can randomly pick up an oncogene while integrating which is then called a viral oncogene
transformation involved stimulating activators of the cell cycle, analouge of cellular oncogene

Question 12

oncogenic retroviruses are divided as follows:

Answer 12

endogenous: passed from mother to daughter animal (germ line), cancer genes
integrated provirus form in DNA
usually totally silent but can emerge in response to stimuli, reasons to cancerogenic chemicals, can lead to production of virions
exogenous: not born with it, typical infectious virus like HIV
most of these are defective in replication because when they pick up an oncogene, they replace some of the viral genome with cellular gene. then need an helper virus with normal replication to provide missing component of their genome in order for oncogene to be expressed. rarely, retroviruses pick up an oncogene that is just added to their genome and they are still competent of replication

Question 13

mechanisms of retroviruses to pick up cellular oncogenes

Answer 13

insertion next to oncogene in host genome, deletion of viral gene/ LTR which is then replaced by the oncogene next to it when transcribed
when the proviral genome is replicated, the machinery reads through the LTR and includes the oncogene after
2 viral strands are incorptorated into viral particle which allows recombination to occur

Question 14

mechanism of tumor production by exogenous retroviruses: acute transforming

Answer 14

introduce a viral oncogene under LTR transcriptional control into host genome. cellular oncogene being driven by viral promoter. rare, chicken flox. usually needs helper virus to produce virus, can cause tumors in weeks. have never been seen in humans

Question 15

mechanism of tumor production by exogenous retroviruses: cis-activating

Answer 15

dont have a viral oncogene but insert in position capable of using viral promoter to drive expression of cellular oncogene = insertional mutagenesis. so provirus is close to c-onc. in mice, murin leukemia virus. none in humans

Question 16

mechanism of tumor production by exogenous retroviruses: trans-activating

Answer 16

produce proteins that regulate genes like tumour suppressors. one example in humans: HTLV-1 (human t cell lymphotropic virus type 1). contains regulatory proteins and RNA. associated with adult t cell leukemia (ATL), all people with this leukemia are infected. transmitted via placenta, sex, breast milk, blood. tax protein and HBZ mRNA drive proliferation of the infected cell (oncogenic). hbz is enough to drive constitutive proliferation and clonal persistance. certain cell stimuli like cell stress and cell activation turn on 5´ promoter and expression of tax mRNA and protein. tax protein causes virion production. HTLV-1 infects CD4+ and cd8+ t cells via GLUT-1 receptor. tax has a transforming role and acts on the LTR region to upregulate expression of gag,pol and env but also acts in trans on various c-onc. tax also acts on enhancers from interkeukin 2 and 2r, promoting t cell proliferation. late stage leukemia cells have low levels of Tax to avoid immune system but higher levels of hbz. HTLV1 can be very far away from oncogene but form a chromatin loop, formed by Ctcf insulator sites, also found on oncogenes. makes the viral enhancer associate with oncogene transcriptional unit.

Question 17

DNA tumor viruses

Answer 17

can be lytic, lack ability to budd out from cell
viral onc genes carried within the virus DNA can randomly be integrated into the host genome. can then control cell cycle.
viral oncogenes are usually unique viral products compared to retrovirus.
transformation often involves inactivation of tumor suppressor genes
transform cells as a consequence of their replication strategy
require host enzymes for replication that are made during s phase so the virus produces proteins that stimulate the cells to move out from G0/G1 to s.

Question 18

tumor suppressor genes that dna viruses interact with

Answer 18

rb protein: controls transition from g1 to s. in the active hypophosphorylated form it associates with the E2F family od transcription factors, sequestering them and putting a break on the cell cycle
p53 protein: TF that induces expression of proteins that arrest the growth of the cell and initiate apoptosis in response to dna damage