Week 4 lec - cancer Flashcards
What is the most prevalent cancer in males?
prostate
what is the second most common cancer among males and females?
colorectal
what is the most common cancer among women?
titty
how many new cancer cases are detected each year world wide?
14 million
how many people die from cancer each year world wide?
8.2 million
what is neoplasia?
Literally means new growth. It is an excessive proliferation that occurs independently of physiologic growth-regulatory stimuli
Three key characteristics of neoplastic growth
- Unregulated by normal physiological mechanisms
- Irreversible
- Monoclonal–arises from a single abnormal cell
A neoplasm is colloquially called a ______
tumour
Is this hyperplasia or neoplasia?
Growth is regulated normally, growth is reversible, can originate in a single cell (monoclonal) or multiple cells
hyperplasia
Is this hyperplasia or neoplasia?
Growth is not regulated by normal physiological mechanisms, growth is not reversible by normal physiological mechanisms, originates in a single cell (monoclonal)
neoplasia
what is the main difference between hyperplasia and neoplasia?
hyperplasia involves a normal (non mutated cell), whereas neoplasia involves a mutated cell
Well-differentiated tumour cells?
bear a close resemblance to the tissue of origin
Poorly differentiated tumour cells?
minimal resemblance to the tissue of origin
Anaplastic tumour cells
(literally ‘backward formation’) = undifferentiated (very poorly differentiated) – no resemblance to tissue of origin
what would you prefer to have, a well-differentiated or poorly differentiated tumour?
The progosis is better for well-differentiated - they are less aggressive and closer to the tissue from where they originated. The drawback is they tend to be a bit harder to treat because of the slower growth rate.
what is the parenchyma?
The proliferating cells of a tumour
what is the supportive stroma?
Connective tissue and blood vessels surrounding tumour, provides the framework on which the parenchymal cells grow
describe a benign tumour
- Margins of the tumour well defined
- Does not invade surrounding tissue or spread distantly
- Generally has a good prognosis, and death is unusual
describe a malignant tumour
- Margins are poorly defined (locally invasive)
- Neoplastic cells destroy surrounding tissue, and spread distantly (metastasize)
- Generally has a poor prognosis
are benign tumours well or poorly differentiated?
well differentiated
do benign tumours have major abnormalities in growth regulation?
no
can benign tumours be fatal?
yes
how can a benign tumour be harmful?
- Compression of adjacent structures (e.g. meningioma)
- Endocrine tumours can secrete hormones (e.g. pituitary adenomas)
are malignant tumours well or poorly differentiated?
can be either
what does metastatize mean?
to spread distantly
what are the 4 mechanisms by which malignant neoplasms can spread? (metastasis)
- *1. Direct invasion** - may invade directly into adjacent organs, or through nerves
- *2. Spread by lymphatics** - to lymph nodes
- *3. Haematogenous spread** (by blood) - to distant sites (common sites
- *4. Transceolomic spread** – abdominal cavity tumours spread directly across peritoneal spaces by seeding of cells that migrate to the surfaces of other organs (technically not considered metastasis)
in metastasis, the tumour deposit is discontinuous with the primary tumour excluding what type of spread?
transcoelomic spread
what are the most typical types of metastasis?
haematogenous or lymphatic spread
what is the risk of basal cell metastasis following melanoma?
<0.1%
A categorically malignant tumour is a tumour that has all three malignant qualities of a cancer. What are they?
- Unlimited and uncontrolled growth
- Invasion of surrounding tissue (direct invasion)
- Potential for distant spread (metastasis)
what would a tumor with one or two malignant qualities be regarded as?
could be classed as benign or malignant - often there is disagreement
is breast fibroadenoma benign or malignant?
benign
is breast carcinoma benign or malignant?
malignant
is colonic polyp (tubular adenoma) benign or malignant?
benign.
event though it has uncontrolled growth and invades surrounding tissue, it does not have metastatic potential.
what is fibroma?
benign neoplasm of fibroblasts
what is adenoma?
benign neoplasm of glands
what is lipoma?
benign neoplasm of adipocytes or lipocytes
what is adenocarcinoma?
malignant epithelial tumour of the glands
what is fibrosarcoma?
malignant mesenchymal (connective tissue, fat, muscle, vessels) lesions of fibroblasts
what is liposarcoma?
malignant mesenchymal (connective tissue, fat, muscle, vessels) lesions of lipocytes
what is leukaemia?
non-epithelial, non-mesenchymal malignant neoplasm of the blood and bone marrow
for benign neoplasms, what suffix do you add?
oma
For malignant epithelial tumours, what suffix do you add?
carcinoma
For malignant mesenchymal (connective tissue, fat, muscle, vessels) lesions, what suffix do you add?
sarcoma
what is Lymphoma?
Non-epithelial, non-mesenchymal malignant neoplasms of lymphoid cells
what is Melanoma?
Non-epithelial, non-mesenchymal malignant neoplasm of melanocytes
what is Mesothelioma?
Non-epithelial, non-mesenchymal malignant neoplasms of mesothelial cells
what is carcinogenesis? (also called oncogenesis and tumorigenesis)
the formation of cancer by transformation of normal cells
how many mutations need to occur for cancer to develop?
multiple, usually at least 2 (ie a mutation in both copies of the gene to make a faulty protein)
Give 3 fundamental changes in cancer cell physiology
Could have picked any of the following:
- Self-sufficiency in growth signals
- Insensitivity to growth-inhibitory signals
- Evasion of apoptosis
- Limitless replicative potential
- Development of sustained angiogenesis
- Ability to invade and metastasize
- Genomic instability resulting from defects in DNA repair
self-sufficiency in growth signals play a part in _____
chose from: neoplasia, hyperplasia
neoplasia
what does TGF-B stand for?
Transforming growth factor beta
what does VEGF stand for?
Vascular endothelial growth factor
what is PDGF?
Platelet derived growth factor
what is EGF?
Epidermal growth factor
what is FGF?
Fibroblast growth factor
which types of cells are the primary producers of growth factors? where does this usually occur?
macrophages and platelets, in sites of injury
Give 3 actions of growth factors
Could have listed any of the followin:
- Chemotaxis (attract more macrophages in chronic and late acute inflammation)
- Fibroblast migration and proliferation
- Angiogenesis
- Increase synthesis of extra-cellular matrix collagen
- Stimulate epithelial proliferation (e.g. in the skin)
RAS/RAF activation is dependent on what?
extracellular signals from growth factors binding to growth factor receptors
a defect in the RAS inactivation protein (called GTPase activating proteins) will result in what?
uninhibited proliferation
what is the most important intracellular pathway affecting proliferation which is often defective in cancer cells?
The RAS/RAF cascade
What type of mutation is responsible for 90% of pancreatic cancers, 50% of colon cancer and 30% of non-small cell lung cancers
RAS mutations (there is usually a defect in the inhibitor binding site caused by a mutation in the 12th amino acid)
what type of mutation is responsible for 70% of melanomas and 0% of papillary thyroid cancers?
RAF mutations
what type of mutation is responsible for 10% of non-small cell lung cancer?
growth factor receptor alterations
what is a proto-oncogene
a normal gene coding for a protein that, when altered (e.g. by mutation), promotes autonomous cell growth
give some examples of proto-oncogenes
Growth factor receptors, RAS and RAF
what are oncogenes?
a mutated gene which codes for abnormal protein synthesis resulting in cancer
what is an oncoprotein?
a protein which has been transcribed and translated from an oncogene
In 20% of breast cancers, there is an overexpression of EGFR2 (epidermal growth factor receptor 2, also called HER2). How does this cause cancer?
It makes the cell sensitive to even tiny amounts of growth factor, resulting in hyperproliferation.
why is HER2 classed as an oncoprotein when overexpressed, even if it’s not mutated?
more HER2 receptors results in the cell being hyperresponsive to growth factor stimulation.
overexpression of _____ ____ ____ _____ is responsible for 20% of breast cancers and 80% of oesophageal cancers.
growth factor receptor alterations
which tumour suppressor gene acts during the G1-S phase checkpoint?
RB
which tumour suppressor gene acts during the G2-M phase checkpoint?
p53
which gene is described as the guardian of the genome?
p53
which gene is mutated in 70% of all cancers?
p53
which intracellular protein induces apoptosis in response to DNA mutations?
p53 (intrinsic apoptosis pathway)
cells with defective p53 tend to be slower or faster-growing cancers?
slower, they evade apoptosis but unless they have a defective proliferation gene (eg RAS) they do not grow faster than normal
give an example of a cancer caused by defective p53
follicular lymphoma
how many replications can most healthy cells undergo?
60-70
what is senescence?
the point at which a cell is no longer undergoing replication
why don’t the telomeres of stem cells shorten?
because they have telomerase
Telomere shortening is recognised by ___ and __
p53 and RB
what can happen if telomerase exists in a cell which is not a stem cell?
CANCER
the cells can undergo an unlimited amount of replications
what do tumours release to promote localised angiogenesis and improve their own blood supply?
VEGF
what are the two phases of metastasis?
- Invasion of extracellular matrix
- Vascular dissemination and homing of tumour cells
H____ I____ F____ helps cancer cells move into the extracellular matrix
Hypoxia inducing factor (also known as HIF)
list the 8 steps of vascular dissemination and homing
- Intravasation (invade into vessels)
- Interaction with immune cells and evasion of destruction
- Formation of tumour cell embolus
- Adhesion to basement membrane
- Extravasation
- Metastatic deposit
- Angiogenesis
- Growth
bet you didn’t get that right, did you?
what is intravasation?
invasion of blood vessels by the cancer cells
what is extravasation
tumour cells leaking from blood into tissues
name the 3 predictions of sites of metastases
- Regional lymph nodes
- Distant metastases based on anatomical relationships
- Non-anatomical tumour specific metastatic patterns
give an example of a type of cancer that usually metastasises in regional lymph nodes
breast carcinoma metastasizes to axillary lymph nodes
give an example of a type of cancer that forms distant metastases based on anatomical relationships
gastrointestinal tumours metastasize to liver
give an example of a type of cancer that has non-anatomical tumour specific metastatic patterns
some carcinomas are prone to bone metastases
give 3 examples of mutagens (things which cause DNA mutations)
sunlight, chemicals, radiation
why are individuals who have an inherited mutation in their BRCA1 or BRCA2 genes more likely to get cancer?
BRCA1 and BRCA2 are DNA repair genes
what type of cancer are people with defective BRCA1 or BRCA2 genes more susceptible to?
breast and ovarian
WHITE MALE PRIVILEGE STRIKES AGAIN
DOWN WITH THE PATRIARCHY
why do faster dividing tumours invade and metastasize earlier?
they develop stepwise genetic alterations faster
What determines a tumour’s growth rate?
- Doubling time of tumour cells
- Fraction of tumour cells in replicating pool (growth fraction)
- Rate at which cells are lost in growing lesion
- Adequate vascular/nutrient supply
what does doubling time mean?
The time taken for a doubling in cell numbers within a neoplasm
is doubling time constant or variable?
variable
what is the growth fraction of a tumour?
The proportion of cells within a tumour that are proliferating
which cells are mainly targeted by chemotherapy?
the ones that are in the growth fraction
