Pathophysiology Review

Question 1

What is cancer?

Answer 1

• Term used for diseases in which abnormal cells divide without control and are able to invade other normal healthy tissues
• Can spread to other parts of the body by the blood and lymph systems
• All Ca’s are believed to be changes in DNA (which make up genes), which make the genes fail to do their jobs and therefore cause problems

Question 2

What are the three models of cancer development?

Answer 2

1) Clonal model
2) Cancer stem cell model
3) Inflammation theory

Question 3

What is the clonal model?

Answer 3

• Suggests initial damage to DNA results in benign tumor growth
• Over time, inheritable genetic changes accumulate and encourage transformation of normal cells into malignant cells
• As more variants in the DNA accumulate, malignant characteristics rapidly proliferate at the expense of less-fit clones

Question 4

What is the cancer stem cell model?

Answer 4

• Cancer is caused by mutated corrupt heterogeneous cancer stem cells
• Among cancer cells, a few act as stem cells that reproduce themselves and sustain Ca growth
• As the tumor grows, the stem cells can enter a rest phase and move back into an active phase years later; this model explains why Ca can return after treatment (therapy affect will be minimal if these stem cells aren’t replicating)
• A variant of this model is the plasticity model, which suggests that non-cancer stem cells with low potential to become tumors can convert to aggressive cancer stem cells

Question 5

What is the inflammation theory of cancer?

Answer 5

Infectious agents and their inflammatory affects, plus chronic inflammation, are the primary cause of cancer

Question 6

What are the different characteristics between malignant and benign tumors?

Answer 6

MALIG:

• Vascular (think angiogenesis)
• Metastatic
• Increased recurrence

BEN:

• Encapsulated
• Well differentiated

Question 7

Define differentiation:

Answer 7

• The process where immature cells become mature cells with specific functions
• In Ca refers to how much or little the tumor tissue looks compared with normal tissue (well = close to normal looking, slow growth) (poor = different, grow fast)

Question 8

What causes metastatis?

Answer 8

Cell breaks off from tumor > enters extracellular space > hormones from tumor cells breaks down basement membrane, allowing cells to break into blood and lymph vessels > tumor cells roll along the vessel endothelial lining until they adhere and enter a new site

Question 9

What is carcinogenesis?

Answer 9

The process of transforming a cell into a cancer cell over 3 phase: initiation, promotion and progression

Question 10

What is the initiation phase of carcinogenesis?

Answer 10

Cells are exposed to an initiating agent, making cells more suspectible to malignant transformation (essentially irreversible DNA changes)

Question 11

What is the promotion phase of carcinogenesis?

Answer 11

• Promoting agents/carcinogens cause unregulated cell growth in previously initiated cells
• Reversible if promoting agents are removed early (eg. drugs, chemicals, hormones)
• Many chemical carcinogens are called a complete carcinogen because they both initiate and promote malignant transformation (eg. smoking)

Question 12

What is a complete carcinogen?

Answer 12

A carcinogen that both initiates and promotes malignant transformation in carcinogenesis (eg. smoking)

Question 13

What is the progression phase of carcinogenesis?

Answer 13

Tumor cells acquire malignant characteristics that include change in growth rate and invasive potential

Question 14

How does cancer spread?

Answer 14

Either by direct invasion into surrounding tissues or by metastasis to distant areas via blood and lymph systems

Question 15

What are the hallmarks of cancer (aka. the six acquired capabilities) of Ca?

Answer 15

1) Ability to sustain proliferation (rapidly producing of new cells) signaling
2) Evasion of growth suppressors
3) Replication immortality (continuous cell cycles with no G0 resting phase and no apoptosis)
4) Resistance of cell death
5) Deregulation of defective DNA repair
6) Angiogenesis
7) Evasion of immune system

Question 16

What is a squamous cell carcinoma?

Answer 16

Malignant, squamous epithelium tumour

Question 17

What is a teratoma?

Answer 17

Benign embryonic tumor

Question 18

What is an adenocarcinoma?

Answer 18

Malignant, ductal/glandular tumor

Question 19

What is an osteosarcoma?

Answer 19

Malignant, bone cell tumor

Question 20

What is an adenoma?

Answer 20

Begin, ductal/glandular tumor

Question 21

What is a lipoma?

Answer 21

Benign fat cell tumor

Question 22

What is lympoma?

Answer 22

Malignant lymph cells

Question 23

What is leukemia?

Answer 23

Malignant WBC’s

Question 24

What is multiple myeloma?

Answer 24

Malignant plasma cells

Question 25

What is rhabdomyosarcoma?

Answer 25

Malignant/benign striated muscle cell

Question 26

What is the growth faction?

Answer 26

Number of cells actively dividing

Question 27

What are check points?

Answer 27

Points where the cell stops to decide to continue to grow or not

Question 28

What is G1 phase? How long does it last?

Answer 28

- Hours to days | - Grow organelles and synthesize proteins

Question 29

What is phase S? How long does it last?

Answer 29

- DNA synthesis complete, copy of DNA in nucleus | - 10-20 hours

Question 30

What is phase G2? How long does it last?

Answer 30

- 2-10 hours - Cell growth, reorganize and prepare to divide; further RNA and protein synthesis - Mitosis begins when G2 ends

Question 31

What is M phase? How long does it last?

Answer 31

- Mitosis, the 'cell division' phase of the cell cycle - Lasts 30-60 minutes - Has it's own separate phases: prophase, metaphase, anaphase and telophase

Question 32

What happens in prophase?

Answer 32

- The first stage of mitosis | - Nucleus breaks and chromosomes condense

Question 33

What happens in metaphase?

Answer 33

- 2nd phase mitosis | - chromosomes line in the center

Question 34

What happens in anaphase?

Answer 34

- 3rd phase mitosis | - separation and moves toward poles (ends)

Question 35

What happens in telophase?

Answer 35

- last phase of mitosis | - daughter chromosomes reach poles and form 2 new nuclei

Question 36

When does G0 phase start?

Answer 36

- Cells meant to divide complete G2 and enter mitosis | - Other types of cells that divide slowly or not at all may exit in G1 phase and enter the non-dividing phase of G0

Question 37

What mutations in the cell cycle allow for Ca growth?

Answer 37

- Most Ca is a result of mutations that make them divide quicker, bypass checkpoints during cell division and avoid apoptosis - Mutations of two cell regulators can promote development of Ca: positive or negative regulators

Question 38

What are positive regulators in the cell cycle in relation to Ca?

Answer 38

- Positive regulators promote cell growth and become hyperactive in Ca cells (known then as oncogenic) - Cell cycle is based on signals (begins when the right signals are present telling it to divide)

Question 39

What are negative regulators in the cell cycle in relation to Ca?

Answer 39

Negative regulators prevent formation of tumors (tumor suppressors) and when to stop growing; may become inactive

Question 40

What is the difference between metaplasia and dysplasia?

Answer 40

Metaplasia - Cell is transformed to another cell type | Dysplasia - cells vary in size, shape and orientation

Question 41

What are proto-oncogenes?

Answer 41

- Genes responsible for making cells divide - Changes in these genes cause oncogenes (therefore making cells divide without the signals to start or stop) - Act as the "gas pedal" of the car

Question 42

What are tumor suppressors?

Answer 42

Genes that act as "the brakes" on cell division

Question 43

How do cells normally grow?

Answer 43

- Normal cells need signals to stimulate growth and when to stop; these signals are ligands like growth factors or inhibitors - These signals are transmitted into the cell via receptors (eg. the tyrasine kinase protein)

Question 44

What is autocrine stimulation?

Answer 44

The ability of a tumor cell to produce it's own growth factors, which then leave the cell, attach to extracellular receptors, and stimulates cell activity and division

Question 45

What is gene amplification?

Answer 45

- Normal cells - surface receptors are restricted (as designed by genes) - In Ca cells, mutations in genes for receptors can occur and if too many genes responsible for receptors are produced, this is called gene amplification (over-expression of receptors) - Some of these receptors may even work without ligands to stimulate them! - End result of growth factor signaling is mitosis

Question 46

What do cancer treatments target?

Answer 46

- Receptors - Ligands that attach to receptors (MAb's can attach ligands before it reaches receptors or attach to receptors before the ligands do) - Tyrosine kinase proteins to active activity within the cell - Transcription of the DNA responsible for tumor growth