phase 1 week 4 Flashcards
What is a tumour?
A tumour is formed by an excessive, uncontrolled proliferation of cells as a result of irreversible genetic change which is passed from one tumour cell to its progeny
What is cancer?
A neoplastic disease of which the natural course of which is (often) fatal
For epithelial tumours what is the normal way in which cells change to become cancerous?
normal > dysplasia > benign > pre-malignant > malignant
What is dysplasia?
“Bad growth” - loss of architectural orientation and development of cellular atypic. Cannot yet invade neighbouring tissue so is not cancer
What is metaplasia?
cells change from one differentiated tissue to another. Unstable environment so high chance of mutations in DNA - precursor to dysplasia and cancer
What are some modes of cancer spread?
local invasion
lymphatic spread
blood spread
transcolaemic spread
What do proto-oncogenes do?
Code for proteins that are needed for normal cell proliferation
What is a oncogene?
a mutated proto-ongogene
what are activating mutations?
only certain mutations in a proto-oncogene will convert it to the oncogenic form
What does the activation of proto-oncogenes do?
allows cells to bypass the need for extracellular growth signals
Why are porto-oncogenes described as dominant acting?
only one allele of a photo-oncogene needs to be acquire an activating mutation
What do oncogenes code for?
a hyperactive version of a protein product or normal protein BUT in abnormal quantities at the wrong time in the wrong cell type
What mutations can lead do hyperactive proteins being formed?
point mutation - e.g ras Ki-ras in colon cancer
deletion
chromosomal rearrangement e.g. ber-able in CML
What mutations can cause proteins to be formed in the wrong place, time or amount?
gene amplification (HER2) breast cancer Chromosomal rearrangement - places gene downstream of a promoter e.g lg-myc
What external signals for growth be mutated to lead to cancer?
hormones
peptide growth factors
Give examples of cell surface receptors that can be mutated
HER2
EGFR
Give examples of intracellular molecules that can be mutated?
signal transducers (ras) cyclins (cyclin D) transcription factors (myc)
What can constitutive telomerase expression do?
hay flick limit not reached so the cell is immortalised
What is a benign tumour?
stay localised at their site of origin
What is a malignant tumour?
able to invade and spread to different sites
What are the b and m endings for epithelial tumours?
oma and carcinoma
what are the b and m names for covering epithelium tissues?
papilloma and carconoma
what are the b and m names for glandular epithelial tumours?
adenoma, adenocarcinoma
What are the b and m names for tumours in the epithelium forming organs (e.g. liver)
adenoma
carcinoma e.g. hepatocarcinoma
What are the b and m endings for connective tissue tumours?
oma
sarcoma
what are the b and m names for smooth muscle tumours?
leiomyoma
leiomyosarcoma
what are the b and m names for skeletal muscle tumours?
rhabdomyoma
rhabdomyosarcoma
what are the b and m names for bone forming tumours?
osteoma
osteosarcoma
what are the b and m names for cartilage tumours
chondroma
chondrosarcoma
what are the b and m names for fibrous tumours?
fibroma
fibrosarcoma
what are the b and m names for tumours of blood vessels
angioma
angiosarcoma
what are the b and m names for adipose tissue tumours?
lipoma
liposarcoma
what are the b and m names for lymphoid tumours?
n/a
lymphoma
what are the b and m names for haematopoetic tumours?
n/a
leukaemia
what are the b and m names fir primitive nerve cell tumours?
n/a
neuroblastoma e.g. retinoblastoma
what are the b and m names fir glial cell tumours?
n/a
glioma e.g. astrocytoma
what are the b and m names for tumours in melanocytes?
pigmented naevi
malignant melanoma
what are the b and m names for tumours in the mesothelium?
n/a
malignant mesothelioma
what are the b and m names for tumours in germ cells
teratoma
teratoma, seminoma
How do tumours get an adequate nutrient supply once they are larger than 1-2mm?
secrete VEGF (vascular endothelial growth factor) promotes production of new vascular tubules
what are MMPs?
matrix metalloproteinases (chew up basement membrane)
what is uPA?
urokinase plasminogen activator
What are some risk factors for cancer?
age alcohol cancer-causing substances chronic inflammation diet hormones immunosuppression infectious agents obesity radiation sunlight tobacco
what happens during G1?
growth in mass, centrosome duplication
what happens during s phase?
chromosome duplication - synthesis of DNA
what happens during G2?
cell grows in size, duplicating organelles and preparing for division
what happens during cytokinesis?
cleavage of daughter cells
what are the 5 stages of mitosis?
prophase pro-metaphase metaphase anaphase telophase
what happens during prophase?
chromatin condensation
nucleolus disappears
centrioles move to the poles of the cell
what happens during pro-metaphase?
nuclear membrane dissolves
chromosomes attach to microtubules and begin moving
What happens during metaphase?
spindle fibres align the chromosomes along the middle of the cell nucleus (metaphase plate)
What happens during anaphase?
paired chromosomes separate and move to opposite sides of the cell
What happens during telophase?
chromatids arrive at opposite poles of the cell
new membranes form around the daughter nuclei
chromosomes decondense
spindle fibres disperse
What are cyclin-dependent kinases?
serine / threonine kinases that require the binding of cyclin for full activity
regulate progression through the cell cycle
activity must be tightly regulated
waves of expression of specific cyclins
phosphorylation / dephosphorylation
What are cyclins?
activator proteins that are up - or down - regulated depending on the phase of the cell cycle
What are cyclin-dependent kinase inhibitors?
small proteins that block cdk/cyclin activity either by forming an inactive complex or acting as a competitive CDK ligand
What is the cyclin / cdk complex needed at the end of G1?
CDK4/6 - cyclin D
What is the cyclin / cdk complex needed for progression through mitosis?
CDK1 - cyclin B
What is CDK1 - cyclin B also known as?
maturation promoting factor (MPF)
What are the four well established check points in the cell cycle?
restriction point (G1) DNA damage check points (end of G1 and G2) Metaphase check point
What is cell cycle progression dependent on?
growth factors
the accumulation of which cyclin means that no growth factors are required for the rest of the cell cycle and that cell is committed to cell division?
cyclin D
What acts as the gate keeper at the restriction point?
retinoblastoma (RB)
What is the function of p53?
cellular stress e.g. DNA damage leads to transcription of p53
at low levels this results in p21 expression which arrests the cell cycle and allows time for the DNA to be repaired
at high levels it promotes apoptosis of the cell
What are the benefits and limitations of X-rays?
good for bones
chest X-ray
abdomen limited
What are the benefits and limitations of CT scans?
excellent for bones
chest and abdomen
25 seconds
limited for soft tissues of spine, limbs and brain
What are the benefits and limitations of MRI?
great for brain, spine soft tissues, limbs
less good for abdomen / pelvis
no good for heart or lungs
25 minutes
What is CT?
A modern imaging tool that combines X-rays with computer technology to produce a more detailed, cross-sectional view of the body
How does an MRI work?
Magnetic field around the patient
pulses radio waves
radio waves cause tissues to resonate
a computer measures the rate at which various tissues give of vibrations and converts it into a 2D picture
What are the 3 main stages of life before birth?
pre-implantation
embryonic stage
foetal stage
When is the pre-implantation stage?
week 1
When is the embryonic stage and what does it involve?
weeks 2-8
organogenesis
When is the foetal stage and what does it involve?
weeks 9-38
growth and development
Describe cleavage
mitotic divisions of fertilised oocyte
overall size remains the same
allows passage down narrowest part of the uterine tube (isthmus)
surrounded by a glycoprotein coat - zona pellucida - to prevent premature implantation
Describe morula formation
around day 4, cells maximise contact with each other
a cluster of cells forms held together by tight junctions
enters the uterus
Describe blastocyst formation
first sign of cellular differentiation
inner cell mass - goes on to form embryo and extra-embryonic tissues
outer cells form trophoblast - contributes to placenta
fluid enters via the zona pellucida into the spaces of the inner cell mass
A fluid-filled blastocyst cavity forms
What causes the blastocyst to “hatch”
ICM cells undergo proliferation and fluid builds up in cavity
eventually blastocyst “hatches” from the zona pellucida to facilitate implantation
What happens in week 2?
implantation
what days does implantation occur?
7-12
Which cells implant first?
trophoblast
What does the trophoblast differentiate into?
cytotrophoblast
syncytotrophoblast
what makes up the bilaminal disk?
the epiblast and the hypoblast
Describe the amnion
continuous with the epiblast
persists until birth
cavity fills with amniotic fluid
protection for developing embryo
Describe the yolk sac
continuous with the hypoblast
important for nutrient transfer in weeks 2-3
disappears around week 20
Describe the chorion
trophoblast and extra embryonic mesoderm
forms foetal component of placenta
chorionic cavity seen early in pregnancy disappears when amnion expands
What is gastrulation?
a process of cell division and migration resulting in the formation of three germ layers
What are the three germ layers?
ectoderm
mesoderm
endoderm
Describe the formation of the three germ alters
once the cells have invaginated, some displace the hypoblast creating the endoderm and others between the epiblast and the newly created endoderm form the mesoderm
the remaining cells in the epiblast form the ectoderm
the cells in these layers give rise to all tissues and organs in the embryo
Describe gap junction communication
sieve like structure at plasma membranes of opposing cells
hemi-channels composed of connexin molecules
Hemi-Channels of one cell align with those of another
physical sharing of ions and small cytoplasmic molecules
cells behave as a syncytium
What is endocrine signalling?
long range (blood) e.g. oestrogen
What is paracrine signalling?
local - neighbouring cells (via diffusion)
e.g. epidermal growth factor
What is autocrine signalling?
same cell
insulin-like growth factor 1
what is juxtracrine signalling?
signal adjacent to receptor
e.g. laminin
What is intracrine signalling?
signal produced in cell acts on nuclear or internalised receptor
e.g. fibroblast growth factor 11
How do steroids work?
diffuse across plasma membrane
bind directly to intracellular receptors
hormone-receptor complex acts as a transcription factor
Affects gene expression directly
