Pathophysiology Review Flashcards
What is cancer?
- 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
What are the three models of cancer development?
1) Clonal model
2) Cancer stem cell model
3) Inflammation theory
What is the clonal model?
- 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
What is the cancer stem cell model?
- 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
What is the inflammation theory of cancer?
Infectious agents and their inflammatory affects, plus chronic inflammation, are the primary cause of cancer
What are the different characteristics between malignant and benign tumors?
MALIG:
- Vascular (think angiogenesis)
- Metastatic
- Increased recurrence
BEN:
- Encapsulated
- Well differentiated
Define differentiation:
- 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)
What causes metastatis?
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
What is carcinogenesis?
The process of transforming a cell into a cancer cell over 3 phase: initiation, promotion and progression
What is the initiation phase of carcinogenesis?
Cells are exposed to an initiating agent, making cells more suspectible to malignant transformation (essentially irreversible DNA changes)
What is the promotion phase of carcinogenesis?
- 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)
What is a complete carcinogen?
A carcinogen that both initiates and promotes malignant transformation in carcinogenesis (eg. smoking)
What is the progression phase of carcinogenesis?
Tumor cells acquire malignant characteristics that include change in growth rate and invasive potential
How does cancer spread?
Either by direct invasion into surrounding tissues or by metastasis to distant areas via blood and lymph systems
What are the hallmarks of cancer (aka. the six acquired capabilities) of Ca?
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
What is a squamous cell carcinoma?
Malignant, squamous epithelium tumour
What is a teratoma?
Benign embryonic tumor
What is an adenocarcinoma?
Malignant, ductal/glandular tumor
What is an osteosarcoma?
Malignant, bone cell tumor
What is an adenoma?
Begin, ductal/glandular tumor
What is a lipoma?
Benign fat cell tumor
What is lympoma?
Malignant lymph cells
What is leukemia?
Malignant WBC’s
What is multiple myeloma?
Malignant plasma cells
What is rhabdomyosarcoma?
Malignant/benign striated muscle cell
What is the growth faction?
Number of cells actively dividing
What are check points?
Points where the cell stops to decide to continue to grow or not
What is G1 phase? How long does it last?
- Hours to days
- Grow organelles and synthesize proteins
What is phase S? How long does it last?
- DNA synthesis complete, copy of DNA in nucleus
- 10-20 hours
What is phase G2? How long does it last?
- 2-10 hours
- Cell growth, reorganize and prepare to divide; further RNA and protein synthesis
- Mitosis begins when G2 ends
What is M phase? How long does it last?
- Mitosis, the ‘cell division’ phase of the cell cycle
- Lasts 30-60 minutes
- Has it’s own separate phases: prophase, metaphase, anaphase and telophase
What happens in prophase?
- The first stage of mitosis
- Nucleus breaks and chromosomes condense
What happens in metaphase?
- 2nd phase mitosis
- chromosomes line in the center
What happens in anaphase?
- 3rd phase mitosis
- separation and moves toward poles (ends)
What happens in telophase?
- last phase of mitosis
- daughter chromosomes reach poles and form 2 new nuclei
When does G0 phase start?
- 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
What mutations in the cell cycle allow for Ca growth?
- 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
What are positive regulators in the cell cycle in relation to Ca?
- 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)
What are negative regulators in the cell cycle in relation to Ca?
Negative regulators prevent formation of tumors (tumor suppressors) and when to stop growing; may become inactive
What is the difference between metaplasia and dysplasia?
Metaplasia - Cell is transformed to another cell type
Dysplasia - cells vary in size, shape and orientation
What are proto-oncogenes?
- 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
What are tumor suppressors?
Genes that act as “the brakes” on cell division
How do cells normally grow?
- 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)
What is autocrine stimulation?
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
What is gene amplification?
- 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
What do cancer treatments target?
- 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
