Unit 2

Question 1

phagocytosis

Answer 1

The process whereby particles or cells are engulfed by cells such as macrophages. Cells that undergo apoptosis are consumed by phagocytosis.

Question 2

proteases

Answer 2

enzyme that degrades proteins

Question 3

caspases

Answer 3

digest substrate proteins at C-terminal of Asp residue

destruction proteins, effectors of apoptosis

the name is derived from 3 of the characteristics of the enzymes: cysteine-rich aspartate proteases

Question 4

autophagy

Answer 4

“eating oneself”

process whereby proteins and organelle components that are no longer required are targeted to the lysosomes for degredation

Question 5

Which one of the following statements about the Bcl-2 family is false?

A. Pro-apoptotic members of the Bcl-2 family are Bax and Bak.

B. The release of important apoptosis mediators from the mitochondria is mediated by the pro-apoptotic members only.

C. Pro-apoptotic and anti-apoptotic members of the Bcl-2 family can interact with each other via protein-protein interactions.

D. Anti-apoptotic factors are Bcl-2 and Bcl-xL.

Answer 5

B

Question 6

Which one of the following statements about apoptosis is false?

A. The aim of conventional chemotherapies is to inhibit apoptosis.

B. In the absence of apoptosis, conventional chemotherapies lead to the accumulation of mutations.

C. For chemotherapy to be successful, cells must be able to trigger apoptosis.

D. Gene mutations that inhibit apoptosis lead to drug resistance.

Answer 6

A

The aim of conventional chemotherapies is to induce apoptosis

B is true

C is true: Most conventional chemotherapies induce extensive DNA damage in order to trigger apoptosis.

D is true: These mutations serve to uncouple drug-induced damage from apoptosis and therefore these tumor cells are resistant to the drug.

Question 7

Which one of the following statements about the apoptosome is correct?

A. Cytochrome B, caspase-9, ATP and Apaf-1 are components of the apoptosome.

B. Cytochrome C, procaspase-9, ATP and Apaf-1 are components of the apoptosome.

C. Bcl-2, ATP, caspase-8 and caspase-9 are components of the apoptosome.

D. Procaspase-9, Bax, cytochrome C and Apaf-1 are components of the apoptosome.

Answer 7

B

A - Cytochrome c and not cytochrome B is a component of the apoptosome.

C - Bcl-2 is an anti-apoptotic protein and caspase-8 is not a component of the apoptosome.

D - Bax resides in the mitochondrial membrane and allows the release of several components of the apoptosome into the cytoplasm.

Question 8

apoptosome

Answer 8

A large quaternary protein structure formed in the process of apoptosis. Its formation is triggered by the release of cytochrome c from the mitochondria in response to an internal or external cell death stimulus.

Question 9

Which one of the following statements about apoptosis is false?

A. It is an important tumor suppression mechanism.

B. It may be triggered by extracellular death signals that act via the extrinsic pathway.

C. It may be triggered by internal stimuli such as DNA damage.

D. It is unregulated cell death characterized by cell swelling.

Answer 9

D

Apoptosis is regulated cell death characterized by cell shrinkage. Cell death characterized by swelling is called necrosis.

A is true: Apoptosis aims to get rid of damaged cells that may otherwise lead to cancer.

B is true

C is true: DNA damage can activate the intrinsic pathway of apoptosis

Question 10

Which one of the following statements is false?

A. Most anti-apoptotic genes are proto-oncogenes.

B. Mutations in Fas receptors have been found in skin cancer.

C. Oncogenic activation of Bcl-2 is associated with lymphoma.

D. Gain of caspase-8 expression is linked with lung cancer.

Answer 10

D

Loss of caspase-8 expression is linked with lung cancer.

Question 11

Which one of the following statements correctly explains why direct apoptotic inducers may be a better drug strategy than conventional chemotherapy?

A. They bypass the need to be mutagenic and avoid therapy related leukemias.

B. They target a host mechanism and not the tumor.

C. They all involve gene therapy

D. They will target tyrosine kinase activity in order to induce apoptosis.

Answer 11

A

B - Direct apoptotic inducers will target the tumor. Anti-angiogenic therapies target a host mechanism.

C - Not all direct apoptotic inducers depend on gene therapy.

D - Tyrosine kinases are not directly involved in inducing apoptosis.

Question 12

Which one of the statements below about the intrinsic pathway of apoptosis is false?

A. The intrinsic pathway is mediated by the mitochondria.

B. The intrinsic pathway of apoptosis depends on death factors TNF and Fas.

C. Internal stimuli, such as DNA damage and oxidative stress, induce the intrinsic pathway of apoptosis.

D. The intermembrane space between the 2 mitochondrial membranes acts as a supply cabinet for apoptotic mediators of the intrinsic pathway.

Answer 12

B

The extrinsic pathway of apoptosis, not the intrinsic pathway, depends on external stimuli such as extracellular death factors.

A is true

C is true - Internal stimuli, such as DNA damage and oxidative stress, induce apoptosis through the Bcl-2 family of proteins that act at the outer mitochondrial membrane.

D is true - because pro-apoptotic Bcl-2 members regulate the release of the apoptotic mediators from this mitochondrial compartment.

Question 13

Drugs being developed as direct apoptotic inducers include all of the following except:

A. Smac mimetics that inhibit XIAP such as birinapant

B. 5-fluorouracil.

C. BH3 mimetics such as ABT-737 and ABT-199.

D. Recombinant human TRAIL.

Answer 13

B

5-fluorouracil is a conventional (anti-metabolite) chemotherapy

A - G-3139 targets Bcl-2 RNA

C - Small molecule inhibitors of Bcl-2, also called BH3 mimetics, such as ABT-737 and ABT-199 are being developed and tested in clinical trials.

D - TRAIL triggers apoptosis in cancer cells and recombinant human TRAIL is being tested in early clinical trials.

Question 14

How does p53 trigger apoptosis?

A. By transcription-dependent means only as mutants that lack a DNA binding domain could not induce apoptosis

B. By transcription-independent means involving direct activation of Bcl-2.

C. By binding directly the death receptors such as Fas.

D. By inducing the transcription of genes that code for pro-apoptotic proteins.

Answer 14

D

P53 can induce the transcription of pro-apoptotic proteins such as Bax.

A - Mutants without a DNA binding domain are able to induce apoptosis.

B - Transcription-independent means of triggering apoptosis include direct activation of Bax.

C - P53 does not interact directly with death receptors.

Question 15

Which statement about alternative cell death pathways is false?

A. Mutations in genes required for autophagy have been linked to carcinogenesis.

B. They use alternative proteases instead of caspases.

C. Important components are stored in the mitochondrial intermembrane space.

D. Drugs that induce alternative cell death pathways are not yet in clinical trials.

Answer 15

D

A vitamin D analog that induces calpain-dependent and caspase-independent cell death is one example of such a drug in clinical trials.

A is true - Specifically evidence for a link of mutations in the gene encoding Beclin and carcinogenesis has been reported.

B is true - Alternative proteases such as calpains, cathepsins, and serine proteases are used in alternative death pathways.

C is true - Apoptosis-inducing factor is one molecule released from the mitochondrial intermembrane space that is involved in alternative cell death pathways.

Question 16

In the laboratory, scientists can detect apoptosis by which of the following methods?

A. RNA interference

B. The TUNEL technique, that uses nick end-labelling

C. Immunoassay

D. Affinity chromatography

Answer 16

B

This technique is able to label the 3’ ends of the many DNA fragments within an apoptotic nucleus.

A, C & D - These techniques are not specific for apoptosis. The TUNEL technique can be used to detect apoptosis.

Question 17

Describe the differences between a necrotic cell and an apoptotic cell.

Answer 17

Necrosis :(

• cell swells, holes appear on plasma membrane, cell bursts and releases intracellular materials
• damages surrounding cells -> inflammation

Apoptosis :)

• programmed cell death
• mild convolution, chromatin condensation, breakdown of nuclear envelope, DNA ladder, proteolysis of target proteins, cleavage of chromatin, blebbing, phagocytosis of apoptotic body
• No damage to surrounding cells

Question 18

IAP

Answer 18

Inhibitor of Apoptosis Proteins

family of proteins that are mainly known for their anti-apoptotic activity and ability to directly bind and inhibit caspases

Question 19

Which one of the following statements correctly describes what happens after Wnt ligand binds to Frizzled and LRP?

a. RAR-RXR heterodimers are formed and associate with HDAC co-repressor complexes, silencing target genes.

b. Axin and APC form a complex with CKI and GSK3β which then modifies β-catenin for degradation.

c. Axin is recruited to the phosphorylated co-receptor LRP and this disrupts the APC, CKI, GSK3β complex.

d. Patched inhibits Smoothened and the pathway is suppressed.

Answer 19

C

The disruption of this complex allows β-catenin to escape degradation, move into the nucleus and act as a co-activator for Tcf/LEF.

A - Incorrect. These are interactions between retinoic acid receptors and HDAC that occurs in the absence of retinoic acid.

B - Incorrect. This process occurs in the absence of Wnt and the modification is the addition of ubiquitin which acts as a molecular flag for β-catenin degradation. It is not the next step after ligand binding.

D - Incorrect. These are events in the Hh pathway in the absence of Hh. Patched and Smoothened are transmembrane proteins. Binding of Hh to Patched relieves Smoothened inhibition and the signal is transduced into the cell.

Question 20

Evidence that the Wnt-signalling pathway is important for self-renewal of stem cells in the adult is:

a. Tcf gene knock-out mice show lack of stem cells in the intestine.

b. Gli mutations lead to skin cancer.

c. APC mutations lead to a lack of stem cells in the intestine.

d. Tcf gene knock-out mice have an increased rate of colon cancer.

Answer 20

A

Tcf is a Wnt-regulated transcription factor and when deleted results in a phenotype that includes lack of stem cells in the intestine.

B - Incorrect. Gli is a transcription factor that is regulated by the Hh signaling pathway and not the Wnt pathway.

C - Incorrect. APC mutations lead to colorectal cancer.

D - Incorrect. Tcf gene knock-out mice show lack of stem cells in the intestine

Question 21

Polycomb group proteins are known as “guardians of stemness”. Which statement about polycomb proteins is true?

a. They induce genes that promote differentiation.

b. They trigger the degradation of differentiation regulators.

c. They repress genes that promote differentiation by epigenetic mechanisms.

d. They repress genes that promote differentiation directly by binding to target gene promoters.

Answer 21

C

Repression involves chromatin compaction and recruitment of methyltransferases.

A - Incorrect. This is false. Polycomb group proteins suppress differentiation of stem cells.

B & D - Incorrect. This is statement is false. They inhibit differentiation regulators by epigenetic means.

Question 22

Mutations that activate the Hedgehog signaling pathway are characteristic of which one of the following?

a. Retinoblastoma.

b. Breast cancer.

c. Colorectal cancer.

d. Basal cell carcinoma.

Answer 22

D

All sporadic basal cell carcinomas possess an activated Hh signaling pathway.

A - Incorrect. Mutations that inactivate Rb are associated with Retinoblastoma.

B - Incorrect. BRCA1/2 genes are associated with familial forms of breast cancer.

C - Incorrect.Mutations that result in activation of the Wnt pathway are found in colorectal cancers.

Question 23

The Hedgehog signal transduction pathway culminates with the induction of target genes by which transcription factor?

a. Gli.

b. b-catenin.

c. Tcf.

d. E2F.

Answer 23

A

Upon binding of Hh, the zinc finger transcription factor Gli is released from the cytoplasm, enters the nucleus and regulates target genes.

B - Incorrect. ß-catenin is a co-transcriptional activator associated with the Wnt signaling pathway.

C - Incorrect. Tcf is a transcription factor that is involved in the Wnt signaling pathway.

D - Incorrect. E2F is a transcription factor which plays a role in cell cycle progression.

Question 24

Which one of the following is the correct name for the treatment of acute promyelocytic leukemia by the administration of all-trans retinoic acid?

a. Differentiation therapy.

b. Apoptotic therapy.

c. Anti-angiogenic therapy.

d. Conventional chemotherapy.

Answer 24

A

Retinoic acid promotes differentiation of cells and its goal is to reverse the leukemic phenotype.

B - Incorrect. Retinoic acid does not directly induce apoptosis.

C - Incorrect. Retinoic acid is not involved in angiogenesis.

D - Incorrect.

Question 25

The chromosomal translocation that is associated with acute promyelocytic leukemia results in the PML-RAR fusion protein. Which statement about how this oncoprotein acts is false?

a. It acts by disrupting the normal role of PML.

b. It acts by associating with HDAC with high affinity.

c. It acts by blocking wild-type receptors and acting in a dominant negative manner.

d. It acts by inducing the EGF pathway.

Answer 25

D

The protein acts by disrupting the normal role of PML, associating with HDAC with high affinity, and blocking wild-type receptors and acting in a dominant negative manner.

Question 26

Which one of the following statements regarding cancer stem cells is false?

a. Cancer stem cells have been identified in many types of cancer.

b. They are a small fraction of tumor cells that maintain the tumor in a cancerous state.

c. They represent one in a hundred tumor cells in acute myeloid leukemia.

d. They do not express the same cell surface markers as stem cells normally present in the tissue.

Answer 26

C

Cancer stem cells represent one in a million tumor cells in acute myeloid leukemia.

A - This is true. Cancer stem cells have been identified in many cancers including pancreatic, breast, brain and prostate.

B - This is true.

D - This statement is true. Cancer stem cells usually express the same cell surface markers as their normal counterpart.

Question 27

What experimental strategy showed that restoration of Apc promotes cell differentiation and re-establishes homeostasis in colorectal cancer in mice?

a. In vitro mutagenesis of the Apc gene

b. PCR and sequence analysis

c. Conditional and reversible control of Apc expression by inducible short hairpin RNAs

d. Microinjection of APC protein

Answer 27

C

Question 28

Which one of the following statements about patients with the syndrome, familial adenomatous polyposis is true?

a. They have a predisposition to basal cell carcinoma and carry a germline mutation in the APC gene.

b. They have a predisposition to developing colon cancer and carry a germline mutation in the Wnt gene.

c. They have a predisposition to developing colon cancer and carry a germline mutation in the RAR gene.

d. They have a predisposition to developing colon cancer and carry a germline mutation in the APC gene.

Answer 28

D

A - This statement is false. They have a predisposition to colon cancer, not basal cell carcinoma.

B & C - This is statement is false. Patients carry a germline mutation in the APC gene.

Question 29

Which one of the following is NOT a valid strategy for the development of new anti-cancer drugs that target cancer stem cells?

a. Small molecule inhibitors of Smoothened.

b. Hedge-hog blocking antibodies.

c. Tyrosine kinase inhibitors targeted against the Frizzled receptor.

d. Creation of compounds that mimic cyclopamine.

Answer 29

C

This is not a valid strategy. Frizzled is not a tyrosine kinase.

A - Incorrect. This is a strategy that has proved successful and has produced an approved drug.

B - Incorrect. These are in development.

D - Incorrect. This is a valid strategy as cyclopamine suppresses the hedgehogpathway by inhibiting smoothened but does not make a good drug itself.

Question 30

What are the 2 characteristics of stem cells?

Answer 30

self-renewal

ability to differentiate

Question 31

Which of the following is the best description of a hematopoietic stem cell?

A. It is the same as an embryonic stem cell.

B. It is more differientiated than an embryonic stem cell.

C. It isn’t stem-cell-like in any way.

Answer 31

B

Question 32

In the Wnt signaling pathway, β-catenin will turn on gene expression if __________.

A. β-catenin has been phosphorylated and ubiquitinated

B. the Axin, APC, CKI, GSK3B complex is functioning as an active kinase

C. β-catenin has entered the nucleus and bound to TCF/Lef

Answer 32

C

Question 33

APC functions as ____.

A. oncogene

B. tumor suppressor gene

C. neither of the above

Answer 33

B

Question 34

PcG (polycomb group) proteins repress transcription of specific sets of developmental regulator genes. They are nicknamed…

A. activators of transcription

B. preventers of cancerous stem cells

C. guardians of stemness

Answer 34

C

Question 35

One therapeutic approach aims to prevent expression of cell proliferation genes by blocking the binding of ______ to Tcf using an inhibitor

A. Wnt

B. Lef

C. LRP

D. β-catenin

Answer 35

D

Question 36

“Cross-seeding” is a term used to describe a process of metastasis that involves:

a. the seeding of metastases from subclones from the primary tumor.

b. one primary tumor seeding two or more other metastases

c. the seeding of metastases from one cell or subclone.

d. the seeding of metastases from subclones from other metastases.

Answer 36

D

A - This is not correct. The seeding of metastases from subclones from the primary tumor can occur but the process is not called cross-seeding.

B - This pattern of metastasis is referred to as “branched”.

C - This pattern of metastasis is referred to as monoclonal seeding.

Question 37

The Epithelial-Mesenchymal Transition (EMT) is:

a. characterized by the production of differentiated-like cells.

b. induced by the transcription factors: HGF and TGFb

c. triggered by the transcription factors: snail, slug, and twist

d. characterized by high E cadherin expression.

Answer 37

C

A - Incorrect. EMT is characterized by the production of stem cell-like cells.

B - Incorrect. HGF and TGFb are growth factors from the tumor stroma and not transcription factors.

D - Incorrect. EMT is characterized by decreased E cadherin expression and high N-cadherin.

Question 38

Which of the following statements about extravasation is true?

a. Strong evidence suggests that cancer cells pass directly through endothelial cells in a process called transcellular transendothelial migration.

b. The steps of extravasation use exactly the same mechanisms compared with intravasation.

c. It is the entry of a tumor cell into a blood or lymphatic vessel.

d. Selectin molecules are important for the attachment of tumor cells to the endothelium.

Answer 38

D

A - This mechanism is currently controversial and only limited evidence supports this view. Cancer cells are thought to move in between endothelial cells.

B - This is incorrect. Different mechanisms are used in these two processes because they approach the endothelium from opposite sides.

C - Incorrect. It is the exit of a tumor cell from a blood or lymphatic vessel.

Question 39

Which of the following statements about disseminated tumor cells (DTCs) are false?

a. DTCs are cells that have spread from a primary tumor but have not yet become a successful metastatic colony.

b. Therapeutic agents that may be able to prevent the reactivation of dormant DTCs are in clinical trials.

c. All DTCs remain dormant.

d. DTCs may be induced to enter a state of quiescence by factors such as those from stable blood vessels.

Answer 39

C

This statement is false. DTCs may be stimulated to grow into secondary tumors called metastases.

A - This statement is true.

B - This statement is true. One anti-fibrotic drug is being tested in clinical trials as an anti-metastatic agent.

D - Experimental data support this statement (Ghajar et al., 2013).

Question 40

Which one of the following statements is false?

a. Micrometastases show net growth.

b. Metastatic colonization requires the growth of new blood vessels.

c. Loss of function of metastasis-suppressor genes results in an increase in metastatic capability.

d. A class of microRNAs that suppress metastasis have been identified and are called metastasis-suppressor microNAs.

Answer 40

A

This statement is false. Micrometastases do not show net growth.

B - This statement is true. Angiogenesis, a process involving the growth of new blood vessels from pre-existing vessels, is needed to provide nutrients and oxygen for the growth of a secondary tumor.

C - This statement is true. Metastasis-suppressor genes are defined by their ability to inhibit overt metastasis without affecting the growth of a primary tumor.

D - This statement is true.

Question 41

There are five important steps involved in metastasis. Which one of the lists below gives the correct order in which these stages occur?

a. Invasion, extravasation, transport, intravasation, and metastatic colonization.

b. Invasion, transport, intravasation, extravasation, and metastatic colonization.

c. Invasion, intravasation, transport, extravasation, and metastatic colonization.

d. Metastatic colonization, intravasation, transport, extravasation, and invasion.

Answer 41

C

Question 42

Which one of the following statements about integrins is false?

a. Their cytoplasmic tails exhibit catalytic activity.

b. They mediate cell-ECM interactions and intracellular signal transduction.

c. Many ligands for integrin receptors contain the amino acid sequence RGD (Arginine, Glycine, and Aspartate).

d. Their binding to suitable ECM ligands inhibits anoikis.

Answer 42

A

This statement is false. Unlike most transmembrane receptors, integrins do not have catalytic tails that exhibit catalytic activity.

B - This statement is true. This includes ‘inside-out’ signaling.

C - This statement is true.

D - This statement is true. Anoikis is triggered in response to lack of ECM ligand binding.

Question 43

Which of the following evidence does not support the concept of the pre-metastatic niche:

a. Conditioned media from one tumor type can redirect the location of metastatic colonization of another tumor type.

b. Breast cancer metastasizes to the lung, one of its closest anatomical organs via the bloodstream.

c. Green-labeled bone marrow cells arrive at a future site of metastasis before red-labeled tumor cells as a result of factors from the primary tumor.

d. Tumor-derived exosomes may act as systemic factors that ‘educate’ bone-marrow derived cells to mobilize to future sites of metastasis.

Answer 43

B

This evidence does not support the pre-metastatic niche but rather that specific metastases can be explained by directionality of blood flow

A, C & D - This evidence supports the concept of the pre-metastatic niche.

Question 44

Which one of the following are not viable therapeutic strategies that target metastasis:

a. Blocking EMT by using tyrosine kinase inhibitors against c-MET.

b. Blocking expression of metastasis suppressor genes.

c. Inhibiting metalloproteinases.

d. Inducing tumor cell dormancy and preventing metastatic niche formation.

Answer 44

B

This is not an appropriate therapy; rather reactivating expression of such genes are being explored in the clinic. MPA is one such agent that has shown induction of the NM23 promoter and is currently in clinical trials.

A - This is a strategy that has produced an approved drug called cabozantinib.

C - Although, no metalloproteinase inhibitor has yet been approved, this is a viable strategy that has been and is being pursued.

D - This is a viable approach and several agents that act in this manner are being tested.

Question 45

Which of the following statements about transport is true?

a. One way we can “see” metastasis is by detecting tumor cells in the bloodstream, called circulating tumor cells.

b. Transport through the bloodstream can be bidirectional with some cells moving with and some against blood flow.

c. Tumor cells never get trapped in capillary vessels as they are too small to do so.

d. Most tumor cells that enter the bloodstream are successful in setting up a metastatic colony.

Answer 45

A

B - Incorrect. Transport through the bloodstream is “one way.

C - Incorrect. A large proportion of tumor cells get physically trapped in capillary beds.

D - Incorrect

Question 46

During metastasis, all of the following processes occur: invasion, intravasation, transport, extravasation, and metastatic colonization. What is the difference between intravasation and extravasation?

A. intravasation is the process where the tumor cells leave circulation and move into the niche where they will live; extravasation is the process where the tumor cells exit the tumor mass to migrate elsewhere

B. intravasation is the process where the tumor cells exit the tumor mass to migrate elsewhere; extravasation is the process where the tumor cells leave circulation and move into the niche where they will live.

C. these terms refer to the movement of vasculature into the tumor mass

Answer 46

B

Question 47

Cancer cells display highest E-cadherin when they are in the ____ state of EMT.

A. epithial

B. mesenchymal

Answer 47

A

Question 48

The seed and soil theory for the site were a tumor metastasizes differs from the pre-metastasis niche theory in that the pre-metastasis niche theory says that the tumor _____.

A. migrated to any of many normal sites in the body that happen to have an environment (soil) where it can survive

B. secretes factors that alter certain environments in the body so they become favorable for the tumor

C. grows so large that it cannot stay in it’s current niche (the pre-metastasis niche), so it has to move out to someplace else

Answer 48

B

Question 49

The tumor ______ is thought to secrete signals (TGF-beta, for example) that induce tumor cells to undergo EMT.

A. nucleus

B. lysosomes

C. stroma

D. mitochondria

Answer 49

C

Question 50

These small vesicle structures released by tumor cells carry proteins and nucleic acids that are shown to establish a pre-metastatic niche.

A. microsomes

B. exosomes

C. endosomes

D. transport bubbles

Answer 50

B

Question 51

What does an integrin receptor bind to? (if there is more than one answer, pick more than one)

A. collagen

B. tubulin

C. fibronectin

D. histones

Answer 51

A and C

Question 52

What is an MMP?

A. metastatic migratory protein

B. a modulator of mitotic progression

C. a matrix metalloproteinase

Answer 52

C

Question 53

VEGF is highly involved in the initiation of angiogenesis. How are angiopoietins and ephrins involved?

A. Angiopoietins and ephrins are classes of drugs that block the action of VEGF.

B. Angiopoietins and ephrins are needed before VEGF can initiate angiogenesis.

C. Angiopoietins and ephrins inhibit the action of VEGF.

D. Angiopoietins and ephrins are important after initiation for vessel maturation.

Answer 53

D

Angiopoietins and ephrins are involved in processes of vessel maturation after VEGF has initiated angiogenesis.

A - Incorrect. Angiopoietins and ephrins are growth factors that further the process of inducing angiogenesis.

B - Incorrect. Angiopoietins and ephrins are involved in processes of vessel maturation after VEGF has initiated angiogenesis.

C - Incorrect. Angiopoietins and ephrins are angiogenic inducers.

Question 54

Which of the following statements about angiogenic vessels are false?

A. The vessels express different integrin receptors compared to mature vessels.

B. The vessels sprout from mature blood vessels.

C. The vessels are straight and stable.

D. The vessels are tortuous and leaky.

Answer 54

C

Question 55

What is the main aim of anti-angiogenic therapy?

A. To target tumor cells directly.

B. To increase cellular response to pro-angiogenic signals.

C. To prevent the formation of new blood vessels.

D. To directly induce apoptosis in tumor cells.

Answer 55

C

A - Incorrect. Rather than targeting tumor cells directly, anti-angiogenic therapy aims at interfering with the responsiveness of host endothelial cells.

B - Incorrect. Anti-angiogenic therapy prevents the cells’ response to pro-angiogenic signals.

D - Incorrect. Apoptotic therapy induces apoptosis directly in tumor cells whereas anti-angiogenic therapy prevents the formation of new blood vessels.

Question 56

Which one of the following statements about anti-angiogenic therapy is false?

A. Angiogenesis only occasionally occurs in adults and so minimal side effects are predicted to occur.

B. Drug resistance is more likely to happen with anti-angiogenic drugs.

C. These drugs are mainly cytostatic, and may need long-term, continuous administration.

D. A different response may be observed between two different types of cancer.

Answer 56

B

This statement is false. Drug resistance is less likely, as target endothelial cells are genetically stable compared to tumor cells which contain many mutations.

A - This statement is true.

C - This statement is true. Anti-angiogenic drugs do not kill tumor cells directly.

D - This statement is true. Avastin was approved for colorectal cancer but showed a variable response for breast cancer and its approval for breast cancer was revoked in 2011.

Question 57

Which one of the following statements is false?

A. Tumors can only form new blood vessels by angiogenesis.

B. Angiogenesis is needed to provide nutrients and oxygen to both primary and metastatic tumors.

C. Circulating endothelial cells derived from the bone marrow can contribute to the tumor vasculature.

D. Tumor cells can act as endothelial cells and form vascular-like structures.

Answer 57

A

This statement is false. Tumors may also form new blood vessels by vasculogenic mimicry and vasculogenesis.

B - This statement is true. Angiogenesis is needed to provide nutrients and oxygen to tumors.

C - This statement is true.

D - This statement is true.

Question 58

During normoxic conditions, degradation of HIFα is signaled by the addition of:

A. Phosphate by a kinase.

B. Ubiquitin via VHL.

C. A hydroxyl group by a hydroxylase.

D. VEGF by a transcription factor.

Answer 58

B

The addition of ubiquitin is a common flag for degradation by proteasomes.

A - Phosphorylation is not involved in this pathway.

C - This is a first step in the pathway but does not directly signal for degradation.

D - VEGF is a target gene of the HIFα transcription factor.

Question 59

How does a tip cell form at the forefront of angiogenic sprouting?

A. By responding to a concentration gradient of VEGF via VEGFR-2.

B. By being pushed forward by stalk cells.

C. By inhibiting the expression and release of DLL4.

D. By producing and releasing VEGF and growing towards the tumor.

Answer 59

A

B - The tip cell is not physically pushed by stalk cells.

C - Activation of VEGFR-2 induces the expression and release of DLL4.

D - The tip cell does not produce VEGF but responds to it.

Question 60

The signal transduction pathway of VEGF is similar to that of EGF except:

A. Ras is only activated in the EGF pathway.

B. One molecule of VEGF binds to two VEGF receptors but one molecule of EGF binds to one EGF receptor.

C. The RAF–MEK–MAPK cascade is only activated in the EGFR pathway.

D. Only dimerization of the VEGFR receptor triggers autophosphorylation.

Answer 60

B

This is true. One molecule of EGF binds to one EGF receptor while only one VEGR molecule binds to two receptors.

A - Ras is activated in both pathways.

C - This cascade is activated in both pathways.

D - Dimerization of both EGF receptor and VEGF receptor leads to autophosphorylation.

Question 61

Conditions of hypoxia stimulate angiogenesis via the hypoxia-inducible-factor-1α alpha (HIF-1α). Which one of the following statements is true?

A. Under hypoxic conditions, the enzyme prolyl 4-hydroxylase is inactivated and allows VEGF to induce the transcription of the HIF-1α gene.

B. Under hypoxic conditions, HIF-1α is covalently modified and targeted for degradation.

C. Under hypoxic conditions, the enzyme prolyl 4-hydroxylase is activated and this leads to angiogenesis.

D. Under hypoxic conditions, the enzyme prolyl 4-hydroxylase is inactivated and allows HIF-1α to induce transcription of target genes, including VEGF.

Answer 61

D

A - This statement is false. VEGF is not a transcription factor and does not induce the transcription of the HIF-1α gene.

B - This statement is false. HIF-1α is covalently modified and targeted for degradation under normoxic conditions.

C - This statement is false. The enzyme prolyl 4-hydroxylase is inactivated under hypoxic conditions.

Question 62

Which one of the strategies listed below has not been developed as an anti-angiogenic drug?

A. Kinase inhibitors targeted against VEGFR.

B. Antibodies targeted against VEGF and VEGFR.

C. Kinase inhibitors targeted against endothelial-specific integrins.

D. Peptide-Fc fusion proteins targeted against angiopoietins.

Answer 62

C

Integrins are not tyrosine kinases and therefore cannot be blocked by tyrosine kinase inhibitors.

A - Several tyrosine kinase inhibitors that target VEGFR have been approved (e.g. Sunitinib, Sorafenib).

B - Avastin and Ramucirumab are examples, respectively.

D - Trebananib is one example.