Neoplasia Flashcards
How many cells are in the human body? How many types? How many die? How many are replaced?
30-40 trillion cells
Over 200+ different cell types
As much 100 billion cells die every day and they are replaced (same number of cells, no net effect)
What is cell division? What is this process called?
One mother cell divides into two daughters cells
Each division is called a cell-cycle
What is neoplasia (tumor)?
New, abnormal, uncontrolled growth of tissue
They do not wait for the signals form the body to for new tissue growth
Ignore the signals to stop dividing (they keep dividing)
Do not differentiate/mature normally
Do not undergo apoptosis/die off to keep the cells numbers constant
What is the difference between benign and malignant tumors?
Benign - not cancer
malignant - cancer
What is adenoma?
Benign tumor derived from glandular cells
ex. breast, lung
What is carcinoma?
Malignant tumor derived from epithelial cells
ex. skin and tissue cells
What is adenocarcinoma?
malignant tumor derived from glandular tissue
ex. prostate, pancreas, mamillary gland, colon
What is sarcoma?
malignant tumor derived from bones or soft tissues
What is lymphoma?
malignant tumor derived from lymphocytes
What is melanoma?
malignant tumor derived from melanocytes
What is leukemia?
malignant tumor of blood-forming tissues
What is blastoma?
malignant tumor derived from precursor cells such as embryonic tissue
What are the four phases of the cell cycle? What occurs at each step? How long are each in dividing cells?
G1, S, G2, M
G1 = Cell grows and prepares to divide
S = DNA replication occurs here
G2 = cell continues to grow and prepares for mitosis (synthesize the proteins needed)
M = No more cell growth and begin division
11hrs, 8hrs, 4hrs, 1hr
What is the G0 phase?
Cell has left the cell cycle and has stopped dividing
What is said about the cell cycle in relation to the number of cells?
The total number of cells in the body remain constant
Cells produced = cells that die
True of False: Cells that enter the G0 phase can re-enter the cell cycle
True, after they receive a specific cell signal
What are permanent cells? Provide an example
Cells that leave the cell cycle that cannot return to the cell cycle
This occurs before the G0/G1 phase
ex) neuron cells - nerve cell damage = no way for the body to replace neurons
What is the G0 phase?
Cell has left the cell cycle and has stopped dividing
Where are the checkpoints for cell division located? What occurs if the cell detects that something is wrong?
G1 checkpoint: DNA synth
G2 checkpoint: prep for mitosis
- Apoptosis occurs if something goes wrong
What occurs in the restriction point (R)?
Cell commits to the cycle for division
The restriction point is 2-3 hors before onset of DNA synthesis
What are the four steps of mitosis?
Prophase - condensation of chromatin and disappearance of the nucleus
Metaphase - xsomes align on the metaphase plate + formation of the mitotic spindle
Anaphase - somes split and move to opposite poles of the cell
Telophase and cytokinesis - Spindle disappears, nucleus reforms and mother cell divides in to two daughter cells
What occurs at the anaphase checkpoint?
The cell checks if the xsomes are attached on the mitotic spindle
If this is not met, then apoptosis
What are the signals that tell the cells to divide? At what point do cells not require these signals?
Growth factors; beyond the R point
What are the cell cycle checkpoints and what is checked at each?
G1/S - checks for nick in the DNA (block the replication, apoptosis)
G2/S - check the blocked replication fork, ds DNA breaks, defects in the centrosome/mitotic spindle (block replication, apoptosis)
Anaphase - any xsome that is not attached to the spindle
What are the major checkpoint monitoring molecules?
Cyclins
Cyclin dependent kinases (CDKs)
p53 - DNA damage - the tumor suppressor
RB - Retinoblastoma
APC- Anaphase promoting complex - protein protease that cleans up non-fxn proteins
What is cell differentiation?
When cells become specialized cells to carry out specific fxns
from Stem cells ——–> differentiated cells
during this process, they gain special structures or lose certain structures
What is cell apoptosis? Explain its mechanism
Cell death.
- Normal cell experiences signal such as chemo, radio, withdraw of GF, death signals
- PM blebbing, cell damage, and increased mito. permeability occur
- Nuclear compaction and further cell shrinkage eventually lead to nuclear fragmentation. The cell dies without damaging the surrounding area
What is cell necrosis? Explain its mechanism
- ischemia-reperfusion and influx of fluid occur
- Cytosol and organelle swelling
- Memb rupture and leakage of proteases and lysosomes
- There is damage to neighboring cells
What is cell autophagy? Explain its mechanism
- Cell starvation - no food, no substrates
- Loss of substrates leads to autophagosome and lysosome fusion
- Exhaustion of substrate
- Loss of organelles due to them being consumed (organelles are destroyed)
- Enzymes eventually released, which can damage other cells/area
What is cell apoptosis mediated by?
Caspase signaling pathways
What is the difference between benign and malignant in terms of cell differentiation?
Benign - differentiated cells mutate and form “differentiated” tumors
Malignant - undifferentiated cells for rapidly dividing tumors
Malignancy decrease when you go down the differentiation process
What are the differences between benign and malignant tumors? List them all
Benign; Malignant
Cells - Similar to normal cells ; Varied shape and sizes with large nucelli
Growth - relatively sloe ; rapid growth, no adhesion
Spread - localized (no movement) ; local and distal metastasis (can move)
Systemic effects - Rare ; often
Life-threatening - Only in certain locations (brain) ; Yes, by tissues destruction and spread of tumors
External surface - smooth ; irregular
Capsule - Yes ; No
Necrosis - No ; yes
Hemorrhage - No ; yes
How are benign tumours diagnosed?
X-ray, ultrasound, mammograms, CT, PET, MRI, blood test, endoscopy, colonoscopy, biopsy
What is the treatment of benign tumors?
Treatment may not be needed
Watch and wait
Surgery
Radiation therapy
How are malignant tumours diagnosed?
X-ray, ultrasound, mammograms, CT, PET, MRI, blood test, endoscopy, colonoscopy, biopsy
What is the treatment for malignant tumors?
Surgery, chemotherapy, radiation therapy, targeted therapy, immunotherapy, biological therapy.
Differentiate what is the primary and secondary treatment for malignant tumors and explain when these treatments take place.
*Primary: Surgery
*Secondary:
- before surgery:
Chemotherapy,
radiation therapy
-Always after therapy:
targeted therapy
immunotherapy
biological therapy.
What is a CT scan?
Computerized Tomography
X-Ray scans from different angles and computer-processed cross-sectional images
What is a PET scan?
Positron Emission Tomography
Use a radioactive drug as a tracer, such as fluorodeoxyglucose
What is a type of macromolecule that cancer cells use?
Sugar
What is an MRI?
Magnetic Resonance Imaging
Uses magnetism, radio waves, and a computer to produce images.
True or false.
The magnetic field in an MRI is very high and if you have a piece of metal on you it can burn your skin.
True
What is a biopsy?
The main way to confirm a diagnosis for most types of cancer.
When do we give a grade level after a biopsy?
When we detect a malignant tumor after a biopsy
What are the six hallmarks of malignant tumors?
- Self-sufficient growth signals
- Constitutively activated growth factor signalling
- Resistance to anti-growth signals
- Inactivated cell cycle checkpoint
- Immortality
- Inactivated cell death pathway
- Resistance to cell death
- Activated anti-cell death signalling
- Sustained angiogenesis
- Activated VEGF signalling
- Invasion and metastasis
- Loss of cell-to-cell interactions, etc.
What does the T represent in the TNM cancer staging system?
Size and the extent of the main tumor (the primary tumor)
* TX: Main tumor cannot be measured
* T0: Main tumor cannot be found
* T1, T2, T3, T4: Refers to the size and/or extent of the main tumor
What does the N represent in the TNM cancer staging system?
Number of nearby lymph nodes that have cancer
* NX: Cancer in nearby lymph nodes cannot be measured
* N0: There is no cancer in nearby lymph nodes
* N1, N2, N3: Refers to the number and location of lymph nodes that contain
cancer
What does the M mean in the TNM cancer staging system?
Whether cancer has metastasized
* MX: Metastasis cannot be measured
* M0: Cancer has not spread to other parts of the body
* M1: Cancer has spread to other parts of the body
Explain the cancer staging numbers
Stage 1:
Relatively small and contained within the organ it started in
Stage 2:
Larger than in stage 1, but has not started to spread into the surrounding tissues
Stage 3:
Cancer is larger, have started to spread into surrounding tissues, and have cancer cells in the local nymph nodes.
Stage 4:
Spread from where it started to another body organ(metastasis)
True or false.
You feel some sort of pain in stage 1 of cancer but not “stage 0”
False.
you don’t feel pain in both stages
What is the cancer grading system?
- GX: Grade cannot be assessed (undetermined grade)
- G1: Well-differentiated (low grade)
- G2: Moderately differentiated (intermediate grade)
- G3: Poorly differentiated (high grade)
- G4: Undifferentiated (high grade)
What makes two things combine together to make a prognosis?
Staging + grading
What does a higher grade is normally associated with what rank of prognosis?
Poorer
What are Paraneoplastic syndromes?
A group of rare disorders triggered by an abnormal immune system response to a cancer
What are some examples of Paraneoplastic syndromes?
- Cushing’s syndrome (hypercortisolism)– small-cell carcinoma
of the lung - Hypercalcemia (high blood calcium level) – squamous cell
carcinoma of the lung - Polycythemia (high number of red blood cells) – renal cell
carcinoma - Venous thrombosis (blood clot in a vein) – pancreatic
carcinoma - Myasthenia gravis (skeletal muscle weakness) – thymoma
What is the leading type of cancer in males and females?
Prostate - breast
True or false.
The higher the GDP the higher the incidence rate for cancer
False
True or false.
The density of each country in the Cancer death rate has a linear relation with cancer rates.
False.
There is no relation between cancer and the density level.
Whats the leading cause of death in Canada?
Cancer
How does the 5-year relative survival rate differentiate between Prostate and Breast cancer stages?
The survival rate for prostate cancer only lowers if cancer spread to other parts of the body, unlike breast cancer which has a linear relation with the death incidence rates.
What is the number one cancer in Canada? How about in Saskatchewan? What is the main reason for this?
Lung cancer; lung cancer
Smoking
What is carcinogenesis?
The formation of new cancer cells in the body
It is not well understood how normal cellular processes become cancerous, but what is associated with cancer?
Genomic stability - DNA instability, chromosome instability
What type of regions are new cancer cells formed?
Hypoxic regions
They can be non-proliferating and not sensitive to drugs (dormant) and/or later recruited to proliferate
What are the exogenous and endogenous causes of carcinogenesis?
Exo: chemical, physical, biological (eg. viruses)
Endo: Oncogenes, tumour suppressor genes
What are examples of chemical carcinogens?
Pesticides -> polychlorobiphenyls (PCBs), pentachlorophenol
Polycyclic aromatic hydrocarbons (they are resistant towards metabolism)
Aromatic amines
Nitrosamines
Steroid hormones
Metals and inorganic compounds
What are the steps of chemical carcinogenesis? Explain each step.
Initiation - Normal cells mutate. The body has detoxification mechanisms, where the cells try to fix the damage. If cannot fix, then the DNA is damaged/destroyed
Promotion - Cell fixing is faulty
Conversion - Fast growing cells; they don’t require signals
Progression - involves invasion, which involves local or lymph/distal regions (thru the blood)
Clonal expansion - Once invaded, the cancer cells need to get bigger
*See notes
What are examples of physical carcinogens?
Ultraviolet light (UV)
X-rays
Radioactive isotopes
Nuclear bombs
Nuclear power plant accidents such as Chernobyl and Fukushima (Radioactive freq causes DNA damage)
Explain the repair of DNA from UV light damage
When UV light hits the DNA strand, two thymines (T) dimerize together, forming a thymine dimer. This results in a kink in the DNA, and DNA polymerase cannot pass thru the DNA. The body has self-repair proteins
What are the three fates of DNA with accumulated or unrepairable damage?
- Senescent cell - cell stops dividing, doesn’t grow, little activity
- Apoptotic cell - programmed cell death
- Cancerous cell - only a small portion of cells become cancerous as this is only 1 of the 3 outcomes
What are examples of biological carcinogens?
Aflatoxin - derived from the fungus Aspergillus flavus; acts as a liver carcinogen
Helicobacter pylori - bacterium in stomach; acts as a gastric carcinogen (debatable)
Schistosoma haematobium - parasite; acts as a urinary bladder carcinogen
Opisthorchis sinensis - Chinese liver fluke; acts as a carcinogen for bile duct of the liver
Human viral carcinogens - DNA and RNA oncogenic viruses
What are the DNA and RNA viruses?
DNA:
Human papilloma virus (HPV)
Epstein-Barr virus (EBV) -> lymphoma
Hepatitis B virus (HBV) -> liver cancer
RNA:
Human T-cell leukemia/lymphoma virus (HTLV-1)
What else can human papilloma virus (HPV) cause?
Cervical cancer
Vulvar cancer
Vaginal cancer
Anal cancer
Genital warts
Head and neck cancer
Penile cancer
What types of genes get mutated in cancer?
Oncogenes are activated
Tumour suppressor genes are inactivated
Explain the normal functions of oncogenes and tumour suppressor genes
Oncogenes - cell growth, gene transcription, migration, metastasis
Tumour suppressor genes - DNA repair, cell cycle control, cell death
What are proto-oncogenes? What happens when they are altered by mutation?
Normal genes encoding normal proteins used in cell division
They become oncogenes and contribute to cancer initiation and progression
What are the normal proteins made by proto-oncogenes?
Growth factors
Growth factor receptors
G proteins
Enzymes that produce second messengers
Genes that turn the production of these proteins on and off
What are the mutations that cause the transformation of proto-oncogenes into oncogenes?
Point mutation - hyperactive protein made in normal amounts (will initiate fast growth)
Gene amplification - more copies made (overproduced)
Xsomal rearrangement - new genes; new regulatory (ex. promoter, etc) ; normal protein to be overproduced and hyperactive fusion protein
Insertion of viral oncogene - insert own genes into host cell. Virus wants to replicate and the host gets the damaged DNA and exhibits cancer
What do oncogenes do?
The still encode proteins needed for cell division
But they may produce: too much protein, and abnormal protein, protein that turns on all by itself, prot made when not needed, prot that cannot turn cell division off, prot that should be made by a different cell
What are tumor suppressor proteins?
The checkpoints usually stop the division of mutated cells
They keep most mutations from developing into cancer
They also do repair and check for DNA damage, if they can’t repair then apoptosis
What are some examples of proteins that control the checkpoints?
Cyclins
Cyclin-dependent kinases
Cyclin inhibitors (p53 - implicated in many human cancer)
If the genes for these proteins were mutated, you might get many more cancers (cancer patients have absent or faulty tumour suppression genes)
What is often the 1st mutation in a developing cancer?
Mutation of the tumour suppressor (ex. P53)
Provide the examples of tumour suppressor genes and their functions?
BRCA1/BRCA2 - DNA ds break repair
p53 - cell-cycle arrest and DNA repair
PTEN - modulation of cell proliferation
pRB - transcriptional co-repressor
PARP - DNA base-excision repair
CIP2A - Inhibition of protein phosphatases 2A
RSK - Kinase
TTK/hMPS1 - Serine, threonine kinase involved in the mitotic spindle spindle assembly checkpoint
What is the “two hit” theory?
Tumour suppressor genes require “two hits” for a cancer to develop (see slide 65 for more details)
Explain the tumour suppressor p53
“the guardian of the genome”
senses genomic damage
suppresses cell replication and growth when there is DNA damage
initiate cell death process if the DNA is irreparable
What is metastasis?
Cancer spreads to a different part of the body from where it started
Travel thru the blood or lymph system
Form a new tumour in other organs or tissues of the body
Metastatic tumour is the same type of cancer as the primary tumour
They are also named after the original site of tumour, for ex. bone metastasized breast cancer
What are the common areas of metastasis?
Liver, lung, lymph nodes, brain, bone
What is the treatment for metastasis?
Reduce growth and the spread of cancer cells
What is migrastatics treatment????????????
Antimetastatic and anti-invasion drugs
Why do cancers prefer to migrate to certain sites?
there are specific sites because organs have good blood supply
The cancer cells need glucose, oxygen, and nutrients
These sites fulfill these requirements
