Cancer Biodiversity

Question 1

“growth in the absence of stimulus” defines what?

Answer 1

Neoplasia.

Question 2

Carcinogenesis describes the process by which a group of neoplastic cells of monoclonal origin accumulate genetic chances until a metastatic phenotype is reached.

Answer 2

Carcinogenesis describes the process by which a group of neoplastic cells of monoclonal origin accumulate genetic chances until a metastatic phenotype is reached.

Question 3

“Well differentiated” means

Answer 3

cell have differentiated correctly and so they look and behave like surrounding tissue.

Question 4

What is a defining feature of early G1?

Answer 4

Mitogen-dependent. Won’t progress without growth signals.

Question 5

What do we call the point where mitogens are no longer required, and borders the early and late G1 phases?

Answer 5

R point

Question 6

What cyclin is dominant in early G1?

Answer 6

Cyclin D (and CDK4,6)

Question 7

What’s that concept for when both alleles need to mutate to become carcinogenic?

Answer 7

The KNUDSON two-hit hypothesis.

Question 8

What is the relationship between active cyclin:CDK complexes, RB and E2F?

Answer 8

E2F mediates S-phase gene transcription.
Constitutively it is inhibited (bound) by the RB protein, which is active in its hypophosphorylated state.
Cyclin/CDK complexes phosphorylate RB, liberating E2F and progressing toward the S phase.

Question 9

What is the first cell cycle checkpoint?

Answer 9

G1/S - checking integrity before replication.

Question 10

What happens in the S phase?

Answer 10

DNA replication

Question 11

Is p53 important in the G1/S or the G2/M checkpoint?

Answer 11

Trick: BOTH.

Question 12

The G2/M checkpoint: checking ______

Answer 12

for DNA damage in replicated DNA prior to mitosis.

Question 13

What do Raf and CDKs have in common?

Answer 13

They’re both Ser-Thr kinases.

Not to be confused with Ras, a regulatory GTPase.

Question 14

Apoptosis can be pathological or physiological. How does that contrast with necrosis?

Answer 14

Necrosis is ONLY pathological.

Question 15

What kicks necrosis off?

Answer 15

Some irreversible injury like ischaemia, which compromises membrane integrity.

Question 16

What are 4 apoptosis triggers?

Answer 16

DNA beyond repair
Disfunctional proteins
Loss of BM adhesion
Immune-mediated apoptosis

Question 17

Apoptosis is important to ____________.

Answer 17

Homeostasis of total cell population.

Question 18

How does breakdown occur in apoptosis? Two important features.

Answer 18

1. ATP dependent degradation;

2. Blebbing into apoptotic bodies for phagocytic clearance.

Question 19

There are two pathways to apoptosis. What is the common feature in both of them?

Answer 19

CASPASE activation.

Question 20

What are the two pathways of apoptosis?

Answer 20

Intrinsic - mitochondrial

Extrinsic - death-receptor (e.g. Fas, the TNF receptor)

Question 21

What triggers intrinsic apoptosis?

Answer 21

Cytochrome C leakage from damaged mitochondria triggers caspase activation.

Question 22

What three processes describe the disordered breakdown of DNA in necrosis?
I lied to Clancy; I didn’t put a hex on you to force you to pick your nose.

Answer 22

pyknosis, karyorrhexia, karolysis

Question 23

What three processes describe the disordered breakdown of DNA in necrosis?

Answer 23

pyknosis, karyorrhexia, karyolysis

Question 24

Apoptotic DNA degradation: chr_________ c_________ followed by _________ into __________ and ______ away.

Answer 24

Chromatin condensation and fragmentation into portions and blebbing away in apoptotic bodies.

Question 25

What two words describe necrosis as a whole process under the microscope?

Answer 25

Swelling and rupture.

Question 26

What does apoptosis look like under the microscope? | 4 aspects.

Answer 26

nuclear shrinkage chromatin condensation membrane integrity preserved blebbing into apoptotic bodies.

Question 27

Describe degradation in necrosis?

Answer 27

Rupture and leaking of contents or enzymatic degradation.

Question 28

Ultimately what triggers necrotic cell death?

Answer 28

ATP depletion and Ca2+ influx.

Question 29

Name the six aspect headings of Apoptosis/Necrosis differences.

Answer 29

``` Process (physiological?) Mechanism/trigger Degradation and dispersal Inflammation? Microscope appearance DNA degradation mechanism ```

Question 30

p53 is pro-apoptotic, an example of an antiapoptotic protein would be ____

Answer 30

BCL2

Question 31

Contact inhitition is a _____ ______ ______

Answer 31

self-regulatory function.

Question 32

Name 8 cancer hallmarks I can't get on the phone to Ms Hewitt - she's gonna help me invase this castle when I can find the philosphophers stone. Once I have that I won't need anyone's help. I can avoid any fear of death. I promise I won't go crazy.

Answer 32

``` Immortality Loss of contact inhibition Tissue invasion/metastasis Genomic instability Angiogenesis Growth factor self-sufficiency Poor differentiation (and pleiomorphism) Evasion of apoptosis. ``` Growth suppressor evasion Immune evasion

Question 33

What process is overcome to achieve immortality?

Answer 33

p53 can sense shortened telomeres and halt cell cycle. This doesn't happen in cancer.

Question 34

How might cancer overcome telomere-related senescence?

Answer 34

Ectopic activation of stem cell telomerases (which lengthen telomeres)

Question 35

What are three methods a cancer can become self-sufficient from growth factors?

Answer 35

1. constitutively active GF receptors. 2. autocrine GF expression 3. overexpression of receptors

Question 36

What are two growth factor receptors famously overexpressed in cancer?

Answer 36

HER2 | EGFR

Question 37

What must a cell be able to do to be metastatic?

Answer 37

De-adhere from other cells and migrate through the basement membrane.

Question 38

What is 1) the molecular and 2) the microscopic hallmarks of a 'mutator' phenotype?

Answer 38

checkpoint dysregulation | abnormal karyotype

Question 39

List 6 cancer risk factors

Answer 39

``` Diet Viral infection UV radiation ionising radiation cigarette smoke environmental pollution ``` Asbestos

Question 40

List 3 work-related carcinogens

Answer 40

Cadmium Aromatic amines - RUBBER workers, DYE workers - bladder polycyclic hydrocarbons - COAL GAS workers - skin/lung

Question 41

Aromatic amines. Who's job is risky?

Answer 41

Rubber and dye workers

Question 42

Polycyclic hydrocarbons. Who's problem?

Answer 42

Coal gas manufacturers.

Question 43

List two non-genetically based risk factors for cancer susceptibility

Answer 43

AGE and GEOGRAPHY | e.g. melanoma in australia

Question 44

What do coal gas manufacturers need to watch out for?

Answer 44

polycyclic hydrocarbons.

Question 45

PHRASES loss-of-function; gain-of-function; loss-of-inhibition

Answer 45

augmentation of endogenous function

Question 46

PHRASES proteins whose activities counteract the hallmarks of cancer, generally related to the cell cycle and cell death.

Answer 46

qualitative or quantitative changes

Question 47

PHRASES inhibit neoplastic growth; constitutive activation

Answer 47

GF, GFr, signal transducers and transcription factors

Question 48

Oncogenes ___ ___ ___ or ___ ___ ___

Answer 48

stimulate cell division or prevent cell death

Question 49

NB Oncogene vs proto-oncogene

Answer 49

NB Oncogene vs proto-oncogene | Unmutated endogenous version

Question 50

Inheretence patterns: Oncogenes TS genes

Answer 50

autosomal dominant | autosomal recessive

Question 51

List three growth factor receptors

Answer 51

RET, EGFR, HER2

Question 52

Transcription factor oncogene

Answer 52

Myc

Question 53

Two ser-thr kinases (oncogenes)

Answer 53

CDKs; Raf

Question 54

Three signal transducing oncogenes

Answer 54

Ras; PI3K Atk

Question 55

What's a GF oncogene?

Answer 55

Gene for PDGF platelet derived growth factor

Question 56

Five TS genes

Answer 56

``` BRCA1 BRCA2 PTEN RB P53 ```

Question 57

Five non-cancer functions. p53 will have a role in them because p53 has a role in damn well everything.

Answer 57

``` cell cycle apoptosis checkpoints senescent Genome integrity ```

Question 58

In order, the type of cell as it progresses through teh carcinogenesis stages.

Answer 58

1. normal cell 2. cell with stem cell like properties 3. mutator phenotype 4. cancer cell monoclonal founder

Question 59

Put the four stages of carcinogenesis in order

Answer 59

1. Initiating mutation 2. Aquisitoin of genetic instability 3. Acquisition of cancer hallmarks 4. Further genetic evolution

Question 60

_____ are constitutively expressed and are activated by ______, which aren't constitutively expressed.

Answer 60

CDK; cyclins