Neoplasia Flashcards
1
Q
Definition: Tumour
A
Originally used to denote a swelling
2
Q
Definition: Cancer
A
Malignant Tumour
3
Q
Definition: Benign
A
Friendly, non-life threatening
4
Q
Definition: Malignant
A
Potentially fatal
5
Q
Definition: Apoptosis
A
Cell suicide or programmed cell death
6
Q
Explain Metastasis
A
- Cancer spreads to a region other than where it originated
- Commonly develop when cancer cells break away from main tumour and enter bloodstream or lymphatic system
- Can also develop when breaking away from main tumour (in belly, abdominal cavity) and grow in nearby areas (liver, lungs or bones)
7
Q
What is Dysplasia?
A
- Abnormal development of cells within tissues or organs
- Can lead to a wide range of conditions involving enlarged tissue or pre-cancerous cells
- Reversible
8
Q
What is Neoplasia?
A
- Uncontrolled, abnormal growth of cells or tissues that is not under physiologic control
o Abnormality = neoplasm or tumour - Irreversible
9
Q
What is Hyperplasia?
A
- Cells are dividing
- Removing initial stimulus will cause additional cells to die from apoptosis
- Increase risk of dysplasia
10
Q
What is Metaplasia?
A
- Change from a well-differentiated cell type to another well-differentiated cell type
- Generally, in response to a change in environment
- Can be reversed by removing the initial stimulus
- Increase risk of dysplasia
11
Q
Definition: In Situ
A
- Tumour confined to its site of origin and has not invaded neighbouring tissue or gone elsewhere in the body
12
Q
Explain Carcinoma
A
- Abnormal cells that divide without control
- Originates in epithelial cells lining the skin or the tissue lining organs, such as the liver or kidneys
- Epithelial cancers increase in incidence as we age
- Cells that are dividing have the greatest chance of sustaining a mutation
13
Q
Atrophy
A
- Occurs at a cellular level an involves the shrinking of a tissue
14
Q
What is Autophagy?
A
- Self-eating so cells shrink
- In response to reduced resources or the removal of damaged organelles
- As we age, the cells’ ability to undergo autophagy declines
o Defective removal of damaged mitochondria results in increased free radical generation
15
Q
Four Classes of Normal Regulatory Genes
A
These genes are principal targets of genetic damage
o Growth promoting proto-oncogenes
o Growth inhibiting tumour suppressing genes
o Genes that regulate apoptosis
o DNA repair genes
16
Q
8 Behavioural Changes that Occur in Cells
A
- Self Sufficiency in Growth Signals
- Insensitivity to growth-inhibitory signals
- Evasion of apoptosis
- Defects in DNA repair
- Limitless Replicative Potential
- Sustained Angiogenesis
- Ability to invade & metastasise
- Predilection for glycolysis even in the presence of oxygen (Warburg Effect)
17
Q
Self-Sufficiency in Growth Signals
A
- Protooncogenes regulate cell proliferation
- Protooncogenes mutate forming oncogenes which promote autonomous growth via the creation of oncoproteins
o Inactivate internal regulator pathways and result in abnormal cell function and transformation - Many cancer cells acquire the ability to synthesise and secrete their own growth factors (creates positive feedback loop)
- Cancer cells can tweak growth factor receptor
o Increases number of receptors on cell surface lower level of growth factor is required to trigger cell division
18
Q
Limitless Replicative Potential
A
- Tumour cells can inactivate senescence signals and activate telomerase
- Telomerase replaces telomeres with base pairs and allows unlimited replication
- Three Cell Types that may show unlimited replication
o Germ Cell (normal)
o Stem Cell (normal)
o Tumour Cells (abnormal)
19
Q
Sustained Angiogenesis
A
- Endothelial cells release plasminogen activator and collangease, breaking down the basement membrane
- Capillaries sprout off venules
- Formation of new blood vessels
20
Q
Evasion of Apoptosis
A
- P53 (guardian of the genome) is responsible for detecting DNA damage, chromosome abnormalities and arresting the cell cycle to initiate repair
o If not possible, apoptosis is induced - More than half of cancers have mutated or missing gene P53
o Therefore, it is damaged or missing - Cancer cells than either increase the activity of inhibitors of P53 or silence the activators of P53
21
Q
Insensitivity to Antigrowth Signals
A
- Antigrowth signals are proteins that inhibit growth
- At a molecular level, nearly all antigrowth signals are funnelled through the Retinoblastoma protein (Tumour Suppressor protein)
o Can be lost through mutation of its gene
o Cancer-promoting proteins (oncoproteins) can block the function of Retinoblastoma - Another antigrowth signal (TGF-Beta) blocks the advancement of cell division when present
o Therefore, cancer cells can reduce the number of TGF-Beta receptors to be irresponsive to its presence
22
Q
Ability to Invade and Metastasise
A
- Primary tumour masses spawn pioneer cells that invade adjacent tissue
- Allows the tumour to colonise a new region of the body in which nutrients and spacer are not limiting
- Successfulness is dependent on the other hallmarks of cancer
23
Q
Warburg Effect
A
- Form of modified cellular metabolism found in cancer cell
o Tend to favour a specialised fermentation over the aerobic respiration pathway - Cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol
o Rather than glycolysis, followed by the oxidation of pyruvate - Aerobic glycolysis produces ATP synthesis promotes cell proliferation by reprogramming metabolism to increase glucose uptake and stimulate lactate production
o High proliferating cancer cells use increased fatty acid synthesis to support the rate of cell division
24
Q
Defects in DNA Repair
A
- Enable cancer cells to accumulate genomic alterations that contribute to their aggressive phenotype
- When erroneous DNA repair leads to mutations/chromosomal aberrations affecting oncogenes and tumour suppressor genes
o Cells undergo malignant transformation resulting in cancerous growth
25
Benign vs Malignant
Benign
- Never metastasises
- Well differentiated
- Homogenous
- Encapsulated
Malignant
- Can potentially metastasise
- Well differentiated or undifferentiated
- Heterogeneous
- Infiltrative growth
26
Benign Tumors of Connective Tissue
- Fibrous Tissue / Fibrocyte / Fibroma
- Muscle / Myocyte / Leiomyoma
- Cartilage / Chondrocytes / Chondroma
- Bone / Osteocyte / Osteoma
- Others include:
o Lipoma
o Haemangioma
27
Malignant Tumors of Connective Tissue
Sarcomas
o Name (Sarc = Malignant + CT cells of origin)
Fibrosarcoma
Leiomyosarcoma
28
Epithelial Benign Tumours
- Papil- (finger like projection)
- Adeno- (relating to glands)
- Cystadena- (cyst like)
- -oma- (denoting tumour and other abnormal growths)
29
Malignant Epithelial Tumors
Carcinomas
- >90% of cancers
o Proliferation, stress
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Example
o Squamous Cell Carcinoma
o Renal Cell Carcinoma
o Adenocarcinoma
o Basal Cell Carcinoma
o Cystadenocarcinoma
o Papillocarcinoma
```
30
Benign Tumors (Other than Epithelial and CT)
- Meningioma (occur in the meninges of the brain or spine)
| - Mature Ovarian Teratoma ‘dermoid cyst’ (germ cell mutates)
31
Testicular Tumors (Malignant)
- Immature Teratoma
| - Seminoma
32
Malignant Tumor Types
- Carcinomas
- Sarcomas
- Testicular Tumours (Germ Cells)
- Mesothelioma (Mesothelial Cells)
- Melanoma (Melanocytes)
- Gliomas
- Lymphomas (Lymphoid Tissue)
- Leukaemias (Hematopoietic Stem Cells)
- Blastomas = Never a normal well-differentiated cell (generally, a childhood cancer)
33
3 Main Routes for Metastasis
- Blood (haematogenous)
o Bone and Soft Tissue Tumours
- Lymphatics (vessels and nodes)
o Melanoma, Breast, Lung and Gastrointestinal Tumours
- Direct Seeding (through/within body cavities)
o Certain tumour cells can only successfully colonise selective organs that have suitable growth environments
34
Importance of Early Detection
- If it is found early, it may be easier to treat
- If cancer has begun to spread, alternative treatment must be utilised
- If cancer has not spread, tumour may have the ability to be removed without further treatment required
35
Signs and Symptoms of Cancer
```
• Location important
• Hormones, blood and mucous
• Cancer Cachexia – Fat and Muscle Loss
• Paraneoplastic syndromes (associated with a hormone imbalance e.g., too much calcium)
o 10-15%
```
36
Cancer Cachexia
- Reduced muscle strength and mass (e.g., sarcopenia)
- Fat loss
- Loss of functional tissue
- Severe fatigue
- Anorexia
- Anaemia and other biochemical changes
37
Treatments
- Surgery – Exercise as much as possible
- Radiotherapy – X Rays
- Chemotherapy – Drugs
- Hormone Therapy – Use hormones or their blockers
Immunotherapy
o Monoclonal antibodies
o Stimulate the immune system to kill the cancer cells
38
Pathogenesis
1. Normal - Multiple Mutation - Cancer
2. Normal - Multiple Mutation - Benign
3. Normal - Multiple Mutation - Benign - Further Mutation - Cancer
4. Normal - Sustained Stress -Metaplasia - Multiple Mutation - Dysplasia - Further Mutation - Cancer
39
Cancer Grading
I-IV
- Estimates how aggressive the cancer is
- Varies depending on the cancer type
- Cytological/Histological examination from biopsy
40
Cancer Staging
TNM
T1-T4 (dependent on size of primary tumour)
N0-N3 (dependent on no. of lymph nodes that have cancerous cells within them)
M0 or M1 (dependent on whether the cancer has metastasised)
