Chapter 7 - Neoplasia Flashcards
(43 cards)
Define Neoplasia
New growth in regards to tumour growth
What is malignant neoplasm?
- Cancerous; associated with altered expression of cellular genes
- Abnormal cell size/shape
- Rapid growth
- May not survive
- Re-occurances
- Poor if untreated
What is benign growth?
- Generally easily cured
- Typical of tissue origin
- Slow and local
- Rare re-occurances
What does -oma and -carcinoma or -sarcoma indicate?
- Benign (adenoma)
- Malginant
Define carcinoma
Epithelial origin
Define Sarcoma
Mesenchymal origin
- Bone, muscles, nerve
Define Leukemia
- Cancer of WBC
- Exception - has its own name
Name the exception to cancer terminology
- Lymphoma
- Hepatoma
- Melanoma
- All are malignant
What are the characteristics of the malignant phenotype
- Ignores growth controlling signals
Anti-social behaviours include:
- Proliferate despite lack of growth initiating signals from environment
- Escape signals die and achieve a kind of immortality (unlimited replication)
- Loss of differentiated features; poor function
- Genetically unstable; evolve by new mutations at fast rate
- Invade local tissue and over-run neighbours
- Gain ability to migrate from origin and colonize at distant sites***
Define Epidemiology and know cancer facts
Epidemiology: study and analysis of patterns, causation, and effects of health and disease conditions in defined populations
Risk Factors
- 2nd leading cause of death in US
- Most cancer deaths occur at age 55+
- Men 1/2 chance
- Women 1/3 Chance
- 5 year survival rate = 68%
- Lung cancer is responsible for most death
List the most important risk factors
- Tobacco
- Nutrition
- Obesity
- Sun exposure
- Sexual Exposure to HPV
Describe tobacco use in regards to lung cancer
Lung Cancer: Leading cause of death in men and women
- Worst survival rate
- More men die than women
Contains carcinogens
- Initiator: causes genetic damage
- Promotor: promotes tutor growth
Define carcinogen
A substance capable of causing cancer in living tissue
Nutrition and Cancer
Dietary factors
- Fat
- Fiber
- Alcohol (liver)
- Antioxidants
Dietary Suggestions
- Limit calorie/alcohol intake
- Increase fibre, fruit, and veggies
Define proto-oncogene
Enhance growth-producing pathways
- Can be transformed into oncogenes by activating mutations
Define tumor supressor genes
Inhibits cell proliferation
- cancer can arise when this gene function is lost/inhibited
Define oncogene
Proto-oncogene in its mutant over active form
Proto-oncogene gain-of-function mutations…
1) Growth Factors (Mitogens)
- Secreted into extracellular space and diffuse to nearby cells to interact with receptor and activate signalling cascade = excessive self-stimulated growth
2) Growth Factor Receptors
- Transmembrane proteins bind with mitogens which activates proliferation = excessive responsiveness (many receptors with abnormal high affinity)
3) Cytoplasmic Signalling Pathways
- numerous enzymes/chemical that transmit signals from activated receptors at cell surface to nucleus; mutant proto-oncogenes can activate this pathway even with no signal
- Ras gene: mutations lead to cancer - stimulates growth with presence of GTP but in malignant cels can be turned on without GTP
4) Transcription Factors
- Proteins must be assembled at promotor area to begin gene transcription and are normally prevented activity until appropriate signal causes release - mutations cause over production / interfere with normal functions of keeping them in check
From Proto-oncogene to Oncogene
-Become activated oncogenes when mutations alter their activity so that proliferation-promoting signals are generated inappropriately
4 general ways for proto-oncogenes activation:
1) Oncogenes introduced to host cell by retrovirus
2) Proto-oncogene within cell suffers a mutagenic event
3) DNA sequence may be lost/damaged and allows proto-oncogene to become abnormally active
4) Error in chromosome replication causes extra copies of proto-oncogene in the genome
Tumor Suppressor Genes
- Act as “BRAKE” to regulate cell growth & prevent mutations
- Slow cell cycle
- Inhibit proliferation of cells due to GFs (growth factors)
- Stop proliferation if cells damaged
- Tumor-Suppressor Genes are inactivated by mutations, which removes BRAKE on cell proliferation
- Contribute to cancer only when not present
- Both copies of tumor suppressor genes are inactivated when cancer develops
- One can inherit a defective copy of tumor suppressor gene
- At much higher risk for cancer development
- Mutations can cause the gene to not function
- Chromosome deletions
- Point mutations
- Nondisjunction
- Epigenetic process
- “Silences” the gene
- Does not require a mutation
Rb Genes
- Normally “master brake” for the cell cycle
- Normally blocks/stops cell division
- Binds transcription factors
- Inhibits these factors from transcribing genes that initiate cell cycle
- Normally can be induced to release transcription factors when sufficiently phosphorylated
- An inactivating mutation of the Rb gene removes restraint on cell division and replication occurs
- Defective Rb gene
- Common in some cancers
The Rb protein functions to bind transcription factors in the nucleus and keep them from participating in the transcription of cell cycle–related genes. pRb is induced to release its hold on the E2F transcription factors when it is sufficiently phosphorylated by cyclin-dependent kinases (Cdk). Cyclin-dependent kinases are activated by cyclin proteins that accumulate when growth factors bind to receptors and stimulate growth pathways. Other signals, such as transforming growth factor-β (TGF-β), inhibit the activity of cyclin/Cdk through activation of inhibitory proteins such as p16. A loss of pRb function removes the “major brake” on cell division. P, Phosphate group; EGF, epidermal growth factor.
p53 Gene
- Most common tumor-suppressor gene defect identified in cancer cells
- More than ½ of all types of human tumors lack functional p53
- Normally p53 inhibits cell cycling
- Accumulates only after cellular (DNA) damage
- Binds to damaged DNA and stalls division to allow DNA to repair itself
- May direct cell to initiate apoptosis
- Mutated or damaged p53 allows genetically damaged/unstable cells to survive and continue to replicate
- Chemotherapy/radiation
- Damages target/cancer cell to trigger p53-mediated cell death
- Cancer cells that lack functional p53 may be resistant to chemotherapy/radiation
Normal vs. Abnormal p53 Gene
-Role of P53 (TP53) in maintaining the integrity of the genome. Damage to DNA in cells with functional P53 stalls the cell cycle so that DNA can be repaired. If repair fails, then the cell undergoes apoptosis to prevent the proliferation of DNA-damaged cells. If the P53 is not functional, genetically unstable cells may be allowed to survive and proliferate.
Normal cell will have small amount of p53
- In case of DNA damage (ex. Hypoxia) this will activate p53 which binds to DNA and stops proliferation to give chance for the cell to repair
- Some cases it is successful
- The same gene also monitors state of cell, and if it cannot heal then the same gene will actually activate apoptosis pathway
- However, when cells contain a mutation of p53 this is no longer possible which means the cell will be able to proliferate regardless of the damage
