Week 9 - Neoplasia Flashcards
what is the mnemonic for the stages of mitosis?
Portugese - prophase - chromosome condensation
Men - metaphase - chromosomes line up and spindle fibres attach
Are - Anaphase - sister chromatids pulled apart
Totally - Telophase - 2 new nuclear membranes form
Cool - cytokenesis - division of cytoplasm
Interphase is anything which isn’t M or G0
cell cycle stages
G1 - growth - protein synthesis G0 - quiescence - when the cell doesn't get signals to keep dividing S - synthesis - DNA replication G2 - growth - protein synthesis M - mitosis
where are the checkpoints?
The first checkpoint occurs between G1 and S, and is creatively named the G1/S checkpoint. It is also known as the restriction point. checks that all the proteins and energy necessary for the S phase are present, that the cell is large enough for the S phase, that its DNA isn’t damaged, and that there are signals from nearby cells, telling the cell to go ahead with division.
The second checkpoint occurs between G2 and M, and is called the G2/M checkpoint. involves checking that the cell has replicated all of its DNA and done any DNA repair that it needs to before entering mitosis
The final checkpoint occurs between metaphase and anaphase, and is called the “spindle checkpoint” or “spindle assembly checkpoint”
what are the two important cell cycle regulators?
cyclins - proteins
G1 cyclins, including cyclin Ds -CD4/CD6
G1/S cyclins, including cyclin Es -CD2
S cyclins, including cyclin As -CD2
M cyclins, including cyclin Bs -CD1
don’t eat any bacon
CDKs - cyclin dependent kinases - remember a kinase is an enzyme which phosphorylates something
these are intrinsic cell cycle factors
what do CDK inhibitors do?
bind to make a CDK-cyclin-inhibitor complex which deactivates the CDK
what is the importance of the retinoblastoma gene?
produces Rb which binds to E2Fs (transcription factors which are commitment factors - push the cell throught the checkpoint to promote entry to S phase) and inhibits them
thus Rb usually inhibits the progression of the cell cycle
a certain level of phosphorylation stops this, leading to cell cycle progression - cyclin D does this
what is atrophy?
either a reduction in number of cells or size of cells
what is dysplasia?
Dysplasia is the abnormal development of a tissue with proliferation of abnormal cells. It is pathological
precancerous
A disturbance in the regular organisation of the epithelium, with varied shapes and sizes of cell (this variation is called pleomorphism)
A larger nucleus:cytoplasm ratio (that is, the nucleus gets bigger within the cell), and hyperchromatic nuclei (these take up more stain than normal, appearing dark). So, big dark nuclei.
Increased mitosis - so they are proliferating faster than normal. This will be shown in a higher prevalence of mitotic figures.
loss of polarity
cell stratification - piling up on top of each other
what is metaplasia?
Metaplasia is the replacement of one type of differentiated cell with another in response to injury
Barrett’s esophagus which occurs when acid reflux disease means that stomach acid repeatedly comes up into the esophagus. The chronic injury and inflammation to the throat leads to the normal stratified squamous epithelium lining it to be replaced by simple columnar epithelium with goblet cells
exposure of the bronchial epithelium persistently to tobacco smoke which injures the epithelium of the bronchial tree and you get a change from the normal pseudostratified columnar epithelium to a squamous epithelium. This called squamous metaplasia as it’s named after the cell it turns into. Can go onto form squamous cancers in smokers.
what is hypertrophy?
increase in size of cells
what is hyperplasia?
increase in number of cells
can be normal such as lactating breast
what is neoplasia?
Neoplasia is the formation of a tumor. A tumor is an abnormal mass of tissue with excessive and uncoordinated growth that persists in the same excessive manner after the stimulus driving it is removed.
what is clonal evolution
cancerous cells have a high rate of mutation, so as the cells divide, they may all arise from a single founder, but certain cells will mutate and then give rise to their own clonal, mutated lines. Therefore the descendants of the same founder cell can be very different from each other.
what is a sessile tumor?
A sessile tumor is a low, flat tumor.
what is an ulcerating tumor?
An ulcerating tumor is one that breaks through the surface of the skin, appearing as a wound. You might also hear them described as fungating, though this just describes a tumor with a mushroom-like appearance which may or may not be true of any ulcerating tumor. Ulcerating tumors are more common in breast, head and neck cancer or in melanoma.
what is an annular tumor?
An annular tumor is most commonly found in colorectal cancer and grows around the surface of the colon and inwards. like build up on the inside of a pipe
what is the difference between an exophytic tumour and an endophytic on?
An exophytic is a tumor that grows outwards from the surface of whatever structure it originated on. Unsurprisingly, an endophytic tumor is one that grows inwards. Exophytic growth is more characteristic of benign growth, and endophytic of malignant, but this is not going to be true 100% of the time.
what is a polyp?
A polyp is a growth of tissue that projects from a mucus membrane (such as those we see in the colon, stomach, uterus, and nasal cavity, among other places). A pedunculated polyp is one which grows on a stalk, sitting on it above the epithelium. exophytic
what is a papillary tumor?
A papillary tumor occurs in finger-like projections, so is exophytic
what are the eight hallmarks of cancer?
- self-sufficiency in growth signaling (cell cycle control)
- evading apoptosis (death pathways)
- limitless replicative potential (immortalisation)
- insensitivity to anti-growth signals (signaling pathways)
- sustained angiogenesis (cytokines)
- tissue invasion & metastasis (adhesion, proteolysis & movement)
- deregulating cellular energetics - aerobic glycolysis
- avoiding immune destruction
what are oncogenes?
Proto-oncogenes are genes that are important in growth control normally, but if mutated, gain a function that drives cancer growth, becoming oncogenes. only need one allele. Ras is a proto-oncogene
what are tumor supressor genes?
Tumor suppressor genes are those which actively work to regulate tissue growth and action, for example by keeping the cell cycle in check. lose function in cancer
need both alleles to lose function
retinoblastoma is a tumor supressor gene
what are the two ways of tumor supressor gene inactivation?
one inherited, one normal - heterozygous - just one mutation needed in each cell. - multiple tumours in both eyes
also in BRCA 1 - breast cancer
BRCA 2 - ovarian cancer
FAP (familial adenomatous polyposis coli) - bowel cancer caused by one inherited mutation of APC gene
APC is a regulatory protein in the Wnt ligand pathway (signalling pathway in tissue organisation and cell-cell signalling). APC regulates β-catenin, which acts as a transcription factor for growth promoting genes. Therefore, mutated APC will not bind β-catenin and so growth becomes uncontrolled (especially in colon).
both sporadic mutation - much rarer - one tumour in one eye
benign tumours
exophytic more differentiated have a capsule do not invade smooth homogenous slow growing
malignant tumours
endophytic less differentiated no capsule invade and metastasise necrosis and irregular heterogenous grow quickly
how does burkitts lymphoma happen?
translocation between 8 and 14
gene for c-myc next to gene which codes for and promotes immunoglobulin G action. The c-myc is left under the control of the IgG enhancers, becoming constitutively active and leading to a cancer of B lymphocytes
what are competence factors?
Competence factors are those that trigger the cell to enter the cycle i.e. to go from g0 to g1
extrinsic cell cycle factor
what are commitment factors?
Commitment factors tend to push the cell through G1 and round the cell cycle. There’s a checkpoint at the end of g1 and the commitment factors are pushing the cell through this checkpoint so that it can complete the cycle once it’s entered the cycle.
extrinsic cell cycle factor
Papilloma
Surface squamous epithelia eg skin, cervix, oesophagus
benign
