Carcinogenesis Flashcards
What is non-neoplastic growth?
Cell growth is because of the cell adapting to its environment –> a normal rxn to some stimulus
What is hypertrophy?
Increase in cell size, can be physiological or pathophysiological.
Example: cardiac hypertrophy.
What is hyperplasia?
Increase in number of cells, referred to as ‘overgrowth’.
Example: lymph nodes, endometrium, ductal hyperplasia of breast.
What happens upon removal of the stimulus for non-neoplastic growth?
Regression of lesion.
What is cancer?
Various malignant conditions characterized by neoplasms.
What is a neoplasm?
Abnormal new growth.
How is cancer characterized?
By proliferation of anaplastic cells that tend to invade surrounding tissue and metastasize to new sites.
What does anaplastic mean?
Less specialized cells.
What does metastasize mean?
Spread throughout the body.
What is neoplasia?
New growth that refers to the process of abnormal cell proliferation resulting in a neoplasm (tumor).
What types can a neoplasm (tumor) be?
Monoclonal (derived from a single cell) or polyclonal (derived from multiple cells).
What is a benign tumor?
Not cancer; tumor cells grow only locally and cannot spread by invasion or metastasis.
What is a malignant tumor?
Cancer; cells invade neighboring tissues, enter blood vessels, and metastasize to different sites.
What are the characteristics of benign tumors?
Grow slower, displace rather than destroy, stay in one place, don’t kill the patient, and cells do not work as well but still function to some extent.
What are the steps leading to a malignant tumor?
- Primary tumor 2. Proliferation/angiogenesis 3. Detachment/invasion 4. Embolism/circulation 5. Transport 6. Arrest in organs 7. Adherence to vessel wall 8. Extravascularization 9. Establishment of a microenvironment 10. Proliferation and angiogenesis 11. Metastasis.
What are the characteristics of malignant tumors?
Grow, spread (direct invasion, metastasis), kill the patient, and create ischemic areas (dead cells).
How do benign tumors differentiate?
Well differentiated, looks more like the tissue of the organ.
What is the rate of growth of benign tumors?
Slower.
What is the local invasion of benign tumors?
No invasion; they don’t leave the capsule or site of origin.
What is the metastasis of benign tumors?
Never.
What is necrosis of benign tumors?
Uncommon.
How do malignant tumors differentiate?
Less differentiated and anaplastic.
What is the rate of growth of malignant tumors?
Faster, but not always.
What is the local invasion of malignant tumors?
Invasive and early on.
What is the metastasis of malignant tumors?
Usually, but not always; if metastasis is present, it is definitely malignant.
What is necrosis of malignant tumors?
Common because they will outgrow blood supply; extensive in the middle of the solitary lesion.
What is the cytology of malignant tumors?
- Pleomorphic (vary in size and shape)
- Hyperchromatic nuclei
- High Nuc/Cyto ratio
- Abnormal mitosis.
What does differentiation mean in the context of neoplastic cells?
Lost in neoplastic cells (no longer specialized).
What is anaplasia?
Primitive disordered cell morphology (hallmark of transformation).
How are benign tumors differentiated?
Well differentiated.
What is the range of malignant cellular change?
Range from well to undifferentiated.
What is the pathway to reach cellular cancer?
Normal –> hyperplasia –> dysplasia –> cancer.
What happens to the balance of new growth and cell death in tumor cells?
It is disrupted.
How does a cell become a detectable clinical mass?
1 transformed cell undergoes at least 30 doublings.
What must happen to cell growth to reach a 1kg mass?
- Total cell cycle time is typically normal
- Rate of loss/doubling
- Doubling time of tumor cells.
What are the characteristics of cancer stages?
- Carcinogen 2. Genotoxic 3. Nongenotoxic.
What are the stages of cancer?
- Initiation 2. Promotion 3. Progression.
What are the stages of cancer progression?
- Normal cell 2. Initiated cell (irreversible) 3. Preneoplastic focal lesion 4. Proliferation (reversible) 5. Neoplasia 6. Malignant metastases.
What causes cancer?
- Direct acting carcinogens
- Chemicals requiring activation (indirect acting carcinogens).
How can changes to DNA occur?
- DNA damage 2. Epigenetic changes.
What are epigenetic changes?
Changes to the chemical groups that associate with DNA that are transmitted to daughter cells after cell division (can occur due to environmental and genetic influences).
What are some epigenetic mechanisms?
- Development
- Environmental chemicals
- Drugs
- Aging
- Diet.
What are the hallmarks of cancer?
- Evading apoptosis
- Self sufficiency in growth signals
- Insensitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential
- Sustained angiogenesis.
What do normal cells require for growth signals?
All normal cells require extrinsic factors produced by other cells.
How is self sufficiency in growth signals achieved in neoplasms?
- Prolong ligand induced signaling
- Increase sensitivity
- Express new receptors
- Make your own growth factors
- Signal in the absence of ligand.
What is an oncogene?
A gene when mutated, amplified or activated, promotes unregulated cell growth (gain of function).
What is an example of an oncogene?
Ras.
What is a tumor suppressor gene (TSG)?
A gene when mutated or inactivated will release cell cycle inhibition (loss of function).
What are examples of TSG?
- Rb and p53.
What is the RAS oncogene?
15-20% of all human cancers have a RAS mutation; normally, RAS is activated by receptors to exchange GDP to GTP; mutant forms of RAS are not inactivated.
How do cancerous cells overcome growth inhibitory signals?
- Most cells in your body are sitting in G0
- Growth inhibitory proteins in the extracellular space
- Terminal differentiation inhibits further cell growth
- Oncogene expression can produce cell cycle arrest.
What is the retinoblastoma protein?
Normally keeps cell in G0 (suppressor function); cell enters S phase and prepares to divide.
What are Rb mutations?
Common in many cancers; inherited (retinoblastomas in children); comprise 80% of small cell lung cancer causes.
What is p53?
50-75% of all cancers have p53 mutation; in normal cells, it suppresses and slows down the cell cycle.
What is evasion of apoptosis?
Cancer cells are resistant to apoptosis due to altered apoptotic machinery, decoy death receptors promoting survival, mutations in intracellular proteins that monitor DNA damage, and increased expression of various anti-apoptotic proteins.
What is necrosis in the context of cancer?
Evidence might do more damage by recruiting tumor promoting inflammatory cells that bring growth stimulating factors.
What is autophagy?
Conflicting data; nutrient starvation, radiotherapy, and drugs induce protective cells.
What is limitless proliferative capacity?
Avoid replicative senescence and avoid crisis.
What is replicative senescence?
Cells have a finite life and ability to replicate; mutations in p53/Rb can extend lifespan; rare mutations lead to immortalization.
What is crisis in cancer cells?
Avoid massive cell death and karyotypic (chromosomal) disarray by activating telomerase.
Why do tumors require angiogenesis?
Often have a necrotic center because blood flow cannot keep up; VEGF activated in tumors signals endothelial cell proliferation and growth of blood vessels.
What is the Warburg hypothesis/effect?
Most cancer cells produce energy by glycolysis due to lack of oxygen.
What kills patients in cancer?
Metastases, not the primary tumor; metastatic cells must be able to enter and leave the bloodstream and survive in ectopic locations.
What is the mechanism of tissue invasion and metastasis?
Invasion metastasis cascade.
What are the enabling characteristics of cancer?
- Genome instability and mutation
- Tumor promoting inflammation.
What are the emerging hallmarks of cancer?
- Deregulating cellular energetics
- Avoiding immune destruction.
