Neoplasia (Patho) - Block 4 Flashcards
All cancer is ____ resulting from damaged DNA and RNA?
Genetic
What are the purines?
Adenine and Guanine
What are the pyrimidines?
Thymine
Cytosime
Uracil
What is redundancy?
Most amino acids are specified by more than one mRNA codon
Before the mitotic phase, the DNA must ___?
replicate
What are the check points of the cell cycle?
- Near the end of G1
- At the G2/M transition
- During metaphase
Describe the process of DNA replication?
- Enzymes unwinds the double helix and expose the bases
- Parental strand acts as a template for synthesis of new strand
- Two new strands (leading and lagging) are synthesized in opposite directions
This process is called semiconservative replication
What is mitotic recombination?
Type of genetic recombination that occurs in somatic cells during their prep for mitosis
Process of abnormal growth of cells.
Neoplasia
Abnormal growth of cells
Tumor (neoplasm)
Condition caused by genetic alterations and defective cell functions?
Cancer
Decreased cell size due to resorption and breakdown
Atrophy
Increased cell size?
Hypertrophy
Increased cell number due to increased reproduction rate
Hyperplasia
Transformation of one differentiated cell to another?
Metaplasia
Abnormal cell development?
Dysplasia
Poor cellular differentiation
Anaplasia
What are the characteristics of benign neoplasms?
Tumor is localized and doesn’t invade or spread to other tissues:
1. Non cancerous
2. Slow development
3. No spreading
4. Well diffentiated
5. Rarely life-threatening
What are the characterisitcs of malignant neoplasms?
Tumor that invades surrounding tissues or spreads to other parts of the body:
1. Cancerous
2. Grows quickly
3. Life-threatening
4. Loss of control of cell division
5. Poorly differentiated
Distinguish the types of malignant neoplasms?
Carcinoma: Epithelial tissue
Sarcoma: Mesenchymal tissue
Leukemias: Hematopoietic or lymphoid tissue
What is a cell cycle?
Period of time from one cell division to the next
What is the function of a cell cycle checkpoint?
To take into account the errors in DNA
What occurs during G1?
Cell growth and DNA is prepared to be copied
* Tumor suppressor stops cell progression
What occurs during S phase?
Copies all chromosomes in the cells
* Tumor suppressor stop progression of the cell cycle and activate DNA repair enzymes.
What occurs during G2 phase?
Production of mitotic spindles and proteins for cell division
What occurs during mitosis?
Division into 2 genetically identical daughter cells
What occurs during G0?
Daughter cells have a temporary or permanent rest from cell division
What are the proteins associated with cell cycle checkpoints?
- Kinase enzymes (catalytic)
- Cyclins (regulatory subunits)
- Proteins that inhibits the kinase enzymes
What activates CDKs?
Cyclins
How are CDKs affected by cancer?
CDK mutations lead to constitutive mitogenic signaling and hyperactivation of CDKs -> tumor formation from amplified and unregulated cell division
What is the overall function of CDKIs?
Promotes tumor suppression
What is differentiation?
Maturation of a normal cell to one with distinct morphology
Describe the grading of cell differntiation?
1-4: The lower number (low grade) is more/well differentiated
What factors affecting the development of cancer?
Genetic and environment alter gene products (proteins) or a cell or tissue
What is a silent point mutation?
A base substitution in the 3rd codon to where gene product is unaltered
What is missense point mutations?
Occur when an ammino acid in the sequence is replaced
What is nonsense point mutation?
Base substitution results in a stop codon -> gene product is truncated and nonfunctional
What is the difference between deletion and isertion?
Deletion: at least one base pair is lost from a sequnce of DNA
Insertion: additional base pairs lead to a frameshift mutation
What is the function of a tumor suppressor gene
Responsible for inhibiting cell replication or braking cell growth
That is considered the guardian of the genome?
TP53
Normal genes responsible for regulation of proliferation of cells.
Proto-oncogenes
Mutated form of a gene that, when upregulated, can allow continuous and ongoing cell growth
Oncogene
When a piece of one chromosome breaks off and fuses to another chromosome
Chromosome translocation
What is the hallmark of leukemias and lymphomas?
Philadelphia chromosome
Suppression of what gene leads to the regression of all tumors when doxycycline is administered?
Myc oncogene
What is the mutator gene?
Increases the rate of mutation of one or more genes
What is microsatellile instability?
Genetic hypermutability -> impaired DNA mismatch repair
What method has the highest frequency of mutations in malignant cells?
Mutator phenotyped
What is clonal expansion?
A cell that acquires a mutation that increases its fitness -> generating more daughter cells than competitor cells that lack that mutation
Specific genes that are responsible for chromosomal instability?
Drivers
Chromosomal deletions are associated most often with what type of tumors?
Solid
An abnormal chromosome number and can involve a loss or gain of chromosomes.
Aneuploidy
An increase in the number of gene copies that results in elevations of the protein without modification of the gene itself.
Gene amplification
What is the function of microRNA?
Noncoding RNA that control gene expression and regulates mRNA exprssion post-transciption
What are the downstreem effects caused by dysregulated microRNA?
- Sustain proliferative signaling
- Evade growth suppressors
- Resist cell death
- Activate invasion and metastasis (angiogenesis)
What are growth facotrs?
Proteins that act outside the cell as chemical signals to regulate cellular behavior
What pathways mediated signal transduction from growth factors?
Ras/Raf/MEK/ERK
What is the function of G proteins?
Singal transducers (on-off switches)
What superfamily is often times mutated to form malignant transformation?
RAS proto-oncogne
What is Loss of heterozygosity?
Mutation that confines genes with recessive status from the loss of one normal copy of a gene or group of genes
The process where normal cells become cancer cells?
Carcinogenesis
Describe the stochastic model
Each cancer cell has the ability to proliferate and form a variety of new tumors from the same tissue of origin
What is the cancer stem cell model?
Suggest that most cells have limited ability to proliferate while the stem cells are responsible for forming sites for growth of new tumors
* Cancer stems don’t rapidly divide making them insensitive to chemo and radiation
What factors stimulate angiogenesis?
- Hypoxia
- Glucose uptake and glycolysis to generate energy
- Lactate is produced -> decreased ATP (Warburg effect)
What is angiogenesis?
VEGF causes the growth of new vessels -> formation of microcirculatory system for the tumor
What GF are overexpressed in cancer?
- EGFR
- HER2
- TGF-b
Changes in proliferative signals
Describe the steps of carcinogenesis?
Initiation: Cancer-causing agent damages DNA
Promotion: Carcinogen introduced to cell -> clonal expansion and acquire mutation (benign)
Progression: Accumulation of mutations -> malignancy
The patterns of spread of cancer cells may depend on what factor?
Host’s immune status
What are the cellular functions of malignant cells?
- Altered cyctoskeletal control
- Prevents normal function of the microtubules
- Modification of external cytoskeleton
- HLA is lost -> cancer cell becomes unidentifiable (Malignant cells are able to masquerade as normal cells)
- Loss of fibronectin
- Alterations in lectin binding
In normal cells, dysregulated glycosylation triggers cell apoptosis through what pathway? How does that compare to tumor cells?
Lectin signaling
In tumor cells the lectin pathway is impaired (TME-mediated alterations in endothelial cell glycosylation)
What are primary tumors?
Tumors that metastasize to organ sites (lung and liver commonly) -> secretion of lytic enzymes to spread cancer
What is the function of ADAMs family protease?
Causes shedding of extracellular domains of GF, cytokines, and adhesion proteins, so they can’t bind along the outside of the plasma membrane -> released by the cancer cells
Examples of inappropriate hormones produced by tumors?
- ObGFs (prostate and breast cancer)
- OcAFs (breast cancer)
- ACTH (neuroendocrine tumors)
What is the most common type of cancer in women? Men? Children?
Breast; prostate; Leukemia (brain or spinal cord are second most common in children)
What are clinical presentations of cancer?
Change in bowel habits
A sore that doesn’t heal
Unusual bleeding or discharge
Thickening or lump in the breat or any part of the body
Indigestion or difficulty swallowing
Obvious change in a mole
Nagging cough or hourseness
What are the clinical manifestations of childhood cancer?
Continued weight loss
Headaches
Increased pain
Lumps
Development of bruising, bleeding, or rash
Hard time sleeping
Obvious paleness
Occur suddenly and persist
Diseases that are uncommon
Constatn infection
A whitish color behind pupil
Nausea
Constant tiredness
Eye changes
Recurring fever of unknown origin
What are the local effects of cancer?
- occlusion
- Destruction of critical structures
- Ulceration
- Tumor infarction
- Abscess formation
Differentiate the cytokines released by tumors in order to produce systemic effects?
TNF: produces cachexia and muscle wasting
IL-6: Secreted during inflammation
PIF: Proteolysis inducing factor
What is cachexia?
Wasting disorder that causes extreme weight loss and muscle wasting, may include loss of body fat
What is the first inidcation that a patient has cancer?
Paraneoplastic syndromes:
1. Endocrine: ectopic hormones
2. Hematologic: anemia
3. Dermatologic: pruritis
4. Neurologic: eripheral neuropathies, cerebellar, and other central neurological paraneoplastic syndromes -> changes in sensations
What are tumor markers?
Molecules in blood, urine, other fluids that indicate a change in tumor growth status
What diagnosis method is used to provide a histology grade of a tumor?
Biopsy: extraction of tissue
1. Fine needle aspiration
2. Core needle
3. Incisional
4. Excisional
What is the difference between the radiographic tests used to identify cancer?
PET: used to identify increased metabolism
CT: Uses a computer to construct a series of cross-sectional scans obtained by examining body organs with X-ray
What is the cancer staging system used globally?
TNM: Tumor, node, meastasis
What are the classifcations of for tumor sites?
Clincal staging: completed at initial workup
Pathologic staging: completed from information identified by the pathologist
Posttherapy staging: Based on info after tx
Retreatment staging: Based on info obtained after exacerbation or disease progression
Autopsy staging: completed upon death of the patient by the med examiner
What is the oldest, most researches, and most sucessful therapy for cancer?
Surger
What are the usual targets of chemotherapy?
Target the cell cycle or specific phases in the cycle
What is radiation therapy?
Used to treat localized cancers through ionized particles
What is the function of biologic therapies to combat cancer?
Enhance the ability of the body to use its natural defenses to fight cancer
Another name for targeted therpaies?
Personalized medicine: targets the hallmarks of cancer growth with less toxicity than conventional chemo
Indications for stem cell transplant?
Uses multiple types of cancer tx: leukemia, lymphoma, myelomas, neuroblastoma, germ cell tumors, ewing sarcoma
