Neoplasia and Apoptosis

Question 1

apoptosis

Answer 1

tightly regulated cell death

Question 2

apoptotic bodies

Answer 2

cells with intact plasma membranes that will be phagocytized by macrophages

Question 3

Does apoptosis have an inflammation component?

Answer 3

no

Question 4

Can apoptosis be physiologic?

Answer 4

yes

Question 5

Can apoptosis by pathologic?

Answer 5

yes

Question 6

Physiologic Apoptosis

Answer 6

embryogenesis, involution due to hormone withdrawal, and self-reactive lymphocytes

Question 7

Pathologic Apoptosis

Answer 7

most commonly due to DNA damage, but can also be accumulation of misfolded proteins, viral infections, or atrophy

Question 8

2 Phases of Apoptosis

Answer 8

1. Initiation Phase
2. Execution Phase

Question 9

2 Pathways in the Initiation Phase

Answer 9

1. Intrinsic (Mitochondrial) Pathway
2. Extrinsic (death receptor) Pathway

Question 10

Which caspase is involved in the intrinsic pathway?

Answer 10

Caspase-9

Question 11

Which caspase is involved in the extrinsic pathway?

Answer 11

Caspase-8

Question 12

Intrinsic (Mitochondrial) Pathway

Answer 12

Bcl protein regulators activated by irreversible cell damage resulting in increased mitochondrial permeability (MOMP) and and release of cytochrome C into cytoplasm which promotes the formation of the apoptosome and caspase 9 activation

Question 13

apoptosome

Answer 13

caspase-activating complex promoted by the release of cytochrome-C

Question 14

MOMP

Answer 14

mitochondrial outer membrane permeabilization

Question 15

Extrinsic (death receptor) pathway

Answer 15

activated by a “death ligand” (FasL) external to the cell [binding to the Fas receptor on cell membrane], then goes through a second messenger cascade via FADD which activates Caspase-8

Question 16

FADD

Answer 16

Fas-Associated Death Domain

Question 17

Are Bcl-2 genes pro or anti apoptotic proteins?

Answer 17

BOTH, mwahaha trick question

Question 18

Main Caspases involved in the execution phase?

Answer 18

Caspase 3, 6, and 7

(MAINLY Caspase-3)

Question 19

Execution Phase

Answer 19

cleaves DNA into small pieces, degrades structural components, and fragments to nucleus

Question 20

Result of the Execution Phase of Apoptosis?

Answer 20

Apoptotic bodies

Question 21

p53

Answer 21

tumor suppressor gene that will prevent propagation of genetically damaged cells when it is activated

Question 22

When is p53 activated?

Answer 22

in response in cellular stress or damage, most often due to DNA damage, but also shortened telomeres and hypoxia

Question 23

3 Ways p53 Prevents Neoplasms

Answer 23

1. Quiescence
2. Senescence
3. Apoptosis

Question 24

quiesence

Answer 24

temporary cell cycle arrest to allow for DNA repair

Question 25

Senescence

Answer 25

permanent cell cycle arrest (if DNA repair fails) and cell continues to live on

Question 26

The ultimate protective mechanism against neoplastic transformation?

Answer 26

APOPTOSIS (you know, the whole focus of this lecture)

Question 27

p53 mutation is present in what % of human cancers?

Answer 27

approximately 50%

Question 28

Factors that can help control apoptosis?

Answer 28

proto-oncogenes, tumor suppressor genes (like p53), and even mutations

Question 29

Without blood vessels, what's the maximum size a tumor could be?

Answer 29

~2mm

Question 30

Mechanism of Angiogenesis

Answer 30

endothelial cells are recruited from pre-existing vessels, then proliferate and migrate through the ECM into tissues, before making their own "capillary bed"

Question 31

Angiogenic Factors (2)

Answer 31

involved in the upregulation of vessel formation 1. Vascular Endothelial Growth Factor (VEGF) 2. Fibroblast Growth Factor (FGF)

Question 32

Antiangiogenic Factors

Answer 32

involved in the downregulation of vessel formation ex: thrombospondin

Question 33

Where do angiogenic and antiangiogenic factors come from?

Answer 33

extracellular matrix (ECM), where they are already present and ready to be used

Question 34

Function of Blood Vessels within Tumors

Answer 34

supply oxygen and nutrients, produce growth factors (PDFG and IL1), and allow for [continued] metastasis

Question 35

Can metastasis occur without VEGF (vascular endothelial growth factor)?

Answer 35

in experiments with mice, nope

Question 36

Morphology of "Capillary Beds" in Tumors

Answer 36

unstable, disorganized, and leaky with no meaningful distribution

Question 37

immunosurveillance

Answer 37

exists to identify and destroy tumor cells

Question 38

What are tumor antigens typically made of?

Answer 38

proteins, glycoproteins, glycolipids, and/or carbohydrates on the surface of tumor cells

Question 39

3 Types of Tumor Antigens

Answer 39

1. Tumor-specific Antigens 2. Tumor-specific SHARED Antigens 3. Tissue-specific Antigens

Question 40

Tumor-Specific Antigens

Answer 40

present within a specific type of tumor and only that specific type ex: proteins produced by papillomavirus

Question 41

Tumor-Specific Shared Antigens

Answer 41

on many different types of tumors (instead of just one), but still absent in normal tissue ex: MAGE family proteins [in human med]

Question 42

Tissue-Specific Antigens

Answer 42

present in the tumors but also the tissue from which they arise from

Question 43

Most common antigen used in determining cell of origin in neoplasms?

Answer 43

tissue-specific

Question 44

First line of defense in the body?

Answer 44

Innate immune system

Question 45

Cells which make up the Innate Immune System

Answer 45

1. NK Cells (Lymphocytes) 2. Macrophages

Question 46

Most effective antitumor defense?

Answer 46

cytotoxic T lymphocytes (CTL, CD8)

Question 47

Cytotoxic T Lymphocytes

Answer 47

targets MHC Class I receptors on tumors and kills cell via cytolysis

Question 48

plasma cells

Answer 48

terminally differentiated B lymphocytes

Question 49

4 Ways in Which Tumors are able to Evade the Immune Response

Answer 49

1. Altered MHC expression 2. Antigen Masking 3. Tolerance 4. Immunosuppression

Question 50

NK cells are activated by what cytokine?

Answer 50

IL-2

Question 51

Antigen Masking

Answer 51

tumors hide the target antigen with other molecules, for example fibrin

Question 52

Tolerance

Answer 52

tumors can have antigens shared with normal tissues, also Tregs

Question 53

Immunosuppression

Answer 53

tumors can produce TGF-a/b to inhibit T lymphocyte activation; tumors can also express FAS ligand which will cause apoptosis of lymphocytes

Question 54

Can benign tumors metastasize?

Answer 54

NO, it is ONLY malignant

Question 55

What % of human cancer deaths are due to metastasis?

Answer 55

90%

Question 56

Is metastasis an efficient process?

Answer 56

no, it takes a lot of time and effort from the neoplastic cells

Question 57

The Steps of Metastasis (6)

Answer 57

1. [Loss of] Adhesion 2. Migration 3. Stromal Invasion 4. Intravasation 5. Tumor Emboli Formation 6. Extravasation

Question 58

Mechanism of Stromal Invasion

Answer 58

release of proteases (from either/both neoplastic and surrounding cells) degrades the basement membrane

Question 59

Intravasation

Answer 59

getting into the blood vessels

Question 60

3 Most Common Pathways of Metastasis

Answer 60

1. Lymphatics 2. Hematogenous 3. Transcoelomic

Question 61

Lymphatic Metastasis

Answer 61

often carcinomas via regional lymph nodes, can be very widespread

Question 62

Hematogenous Metastasis

Answer 62

often sarcomas that travel through the venous system and will deposit themselves at the next capillary bed

Question 63

If you have metastatic hemangiosarcoma in the lung, where is its likely origin?

Answer 63

right atrium of the heart (follow veins backwards)

Question 64

Transcoelomic

Answer 64

often transabdominal, typically carcinomas within a body cavity; jumps between surface of organs