GEP (Life Protection) Week 4 Flashcards
Identify the antomical points
Describe the mammary gland?
Alveoli- hollow structures with milk secreting cells
Lobules- collection of alveoli draining into one lactiferous duct
One mammary gland per breast
Collection of 15-20 lobules
Is a highly modified sweat gland
Describe the connective tissue stroma of the breast?
Connective tissue fascia- fatty and fibrous components for support, contains suspensory ligament of Cooper which attaches attaches breast to dermis and pectoral fascia and separates lobules
Retromammary space
Space where breast implants go
Between breast and pectoral fascia (deep fascia covering pec major)
Identify the anatomical parts
Pectoral=Anterior
Medial=Central
Breast is innervated by anterior and lateral cutaneous branches of 4th and 6th intercostal nerves
What the 3 main types of nodes around the breasts?
75%-> axillary
20%-> parasternal
5%-> posterior intercostal
What are the 3 main sources of blood supply to the breasts?
Medial mammary branch from the internal thoracic artery
lateral mammanry branches of lateral thoracic
Lateral Mammary branches of posterior intercostal arteries
Which veins are involved in the drainage system of the breast
Veins of breast drain into axillary vein + internal thoracic vein
What does Genotype and Phenotype mean?
-Genotype is the instructions written in your DNA
-Phenotype is the characteristics you get from the instructions in your DNA
What factors affect the ways the same genotype can present differently
-Epigenetics- how environment and behaviour cause genetic modifications/ how genes are expressed without changing the DNA sequence
-Incomplete penetrance- when genes in the genotype don’t get expressed in the phenotype
-Variable expression- when genes in the genotype don’t get expressed as strongly
Genetics basics:
-23 pairs of chromosomes (pair= 1 from mother, 1 from father)
-Gene locus- place on chromosome where instructions for gene are found
-Allele- one of the 2 forms of genes (ie one allele to code for same thing on each chromosome)
What is autosomal dominant?
This is where only one mutated allele needed to have disease (for example: huntington’s, Marfan’s, achondroplasia)
what is autosomal recessive?
Need both mutated allele to have disease (for example: CF, sickle cell trait, tay-sachs disease).
what is mitrochondrial inheritance pattern?
Mitochondrial DNA is passed maternally
Eg: mitochondrial myopathy
What is the purpose of the cell cycle?
-To replenish lost or old cells
-Increase cell numbers (like the immune cells during an infection)
-embryonic development
Describe the cell cycle and a brief overview of the different stages?
Interphase (The cell grows and copies its DNA):
-G1: Cell growth
-S: DNA synthesis
-G2: More growth, preparation for mitosis
Mitosis (M phase) (The cell divides its DNA and cytoplasm, forming two new cells) :
-Prophase
-Metaphase
-Anaphase
-Telophase
**G0 (Resting State): Where the cells performs in functions and is not preparing to divide. This done outside the cell cycle.
**
Mitosis: Devision of the neucleus
Cytokinesis: Devision of the cytoplasm and its content
What are cell cycle checkpoints and why are they important?
-Transition from one phase to another requires cells to pass checkpoints → make sure that all the necessary steps are completed and no errors occur
-If cells do not meet the conditions to pass the checkpoints → stop the cell cycle and try to correct errors/commit suicide (apoptosis)
Describe the G0 phase?
Resting phase that happens outside the cell cycle
Different types of cells have different relationships with G0.
Describe the G1 phase of the Interphase
-This is the longest phase of the cell cycle
-Cell accumulates necessary nutrients and proteins to be able to divide (e.g. nucleotides needed for DNA replication in S phase) → cell doubles in size
-Entry to the cell cycle (at G1) requires the stimulation of cells by e.g. growth factors
-Cells do not enter the cell cycle if:
There is no growth factor
The cell is not prepared (e.g. not enough nutrients)
-Checkpoints determine if cells are ready to enter S phase (see later)
Describe the S phase part of Interphase?
The phase of the cell cycle when DNA replication happens (semi-conservative process).
There are 3 phases of DNA replication:
Initiation
Elongation
Termination
Characteristics of DNA:
Double helix
Made up of bases A, G, C and T
Two strands are held together by H-bonding between A-T and G-C
Runs from 5’ to 3’ direction
Antiparallel
Describe Initiation part of the DNA replication that occurs in the S phase?
-DNA is locally unwound at multiple origins of replication.
-DNA is further unwound by DNA helicase → creates the “replication fork” which move further away from each other.
-Unwinding creates supercoiling → supercoiling is relieved by topoisomerases
-ssDNA is stabilised → SSBs (single-stranded DNA-binding proteins)
Topoisomerases cut one or both strands to relieve tension from supercoiling
Describe Elongation part of the DNA replication that occurs in the S phase? (part 1)
-Elongation =replicate DNA
-DNA cannot be freely added to the strand → primase synthesises a short RNA primer complementary to the DNA sequence
-DNA Pol can now bind to the RNA primer → adds bases from 5’ to 3’ direction → continuous replication of the leading strand (5’→3’) & staggered replication of the lagging strand (3’→5’)
Characteristics of DNA Pol (polymerase):
Cannot bind free nucleotides → cannot synthesise DNA without an RNA primer
Can only synthesise DNA from 5’ to 3’ → need for Okazaki fragments (on lagging strand)
Describe Elongation part of the DNA replication that occurs in the S phase? (part 2)
DNA Pol can only synthesise DNA in the 5’→3’ direction → lagging strand is synthesised in the “opposite direction” in a staggered manner
RNA primer is made by primase → DNA Pol synthesises DNA 5’→3’ until it bumps into the previous RNA primer → resulting fragments are called Okazaki fragments
Describe Termination part of the DNA replication that occurs in the S phase?
Termination= Finish replication
-An endonuclease removes the RNA primers
-DNA Pol fills the gap
-DNA ligase joins the Okazaki fragments
-DNA Pol can proofread the resulting DNA copy → prevents mutation in most cases
What does Semi-conservative process mean in DNA Replication
Semi-conservative process → one strand of the newly replicated DNA is made up of the old DNA template, while the other strand is newly synthesized
Describe the G2 phase of the cell cycle?
-At the end of the S phase, the DNA content of the cell is doubled.
-So now the role of the G2 phase is Synthesis of cellular components for mitosis (e.g. centrioles, mitotic spindle)
Correct mistakes of DNA replication (or commit apoptosis)
A checkpoint at the end of G2 determines if the cell can continue to M phase and divide
Describe the M phase?
Mitosis → division of the nuclear content
Prophase
Metaphase → metaphase checkpoint
Anaphase
Telophase
Cytokinesis → division of the cytoplasm
What are cell cycle checkpoints and what are its goals?
-Cells only replicate when they need to
-DNA replication is done with high fidelity (i.e. no errors)
-Chromosomes are segregated accurately
-The cell cycle progresses in the correct order
Describe the different cell cycle checkpoints?
- Restriction point → entry into the cell cycle from G0
- G1/S checkpoint → initiation of S phase
Check for → cell size, nutrients, DNA damage, growth factors
Key proteins → Rb and p53 - Intra S phase checkpoint
Check for → DNA damage - G2/M checkpoint → entry into mitosis
Check for → DNA damage, presence of proteins needed for mitosis - Metaphase/mitotic spindle checkpoint
Check for → all chromosomes have spindles attached
Describe the cell cyle regulator Cyclins-Dependent (CDKs)?
-Kinases = proteins that add phosphate groups to other proteins → phosphorylation is one of the major ways of controlling protein function
-Stable levels during the cell cycle
-Get activated by cyclins binding to them → when the cyclin is degraded, CDKs become inactivated
Describe how INK4 family of CKIs work in the G1 phase?
How does CIP/KIP family of CKIs work in G1/S phase junction and S phase (part 1)?
-Controls entry into S phase (DNA replication) - involves Rb and E2F
-If there are enough nutrients, the cell is big enough & there are growth factors present → activate the G1-specific cyclin/CDK complex
-This cyclin/CDK complex will phosphorylate the retinoblastoma protein (Rb)
-Rb releases E2F → it works as a transcription factor to synthesise the S phase-specific cyclin → beginning of S phase
Rb is a tumour suppressor which is mutated in retinoblastoma
How does CIP/KIP family of CKIs work in G1/S phase junction and S phase (part 2)?
Ensures that DNA damage is repaired and not passed on to the daughter cells.
p53 detects DNA damage → pauses the cell cycle
Correct replication errors (DNA repair)
Apoptosis
p53 is a tumour suppressor which is mutated in number of different cancers
Summary of the Cell Cycle 1 (Not a question)
Summary of the Cell Cycle 1 (Not a question)
Describe the process of carcinogenesis?
-Initiation → initiating mutation
-Promotion → selective growth advantage for other mutations in important genes (proto-oncogenes or tumour suppressor genes)
-Progression → enhanced cell division due to other mutations (invades the surrounding stroma)
-Metastasis → invasion of secondary tissues via the bloodstream/lymphatics
Cancer can be initiated by mutations in either proto-oncogenes (giving rise to oncogenes) or tumour suppressor genes.
What is Knudson’s two hit hypothesis?
= loss-of-function mutations need to affect both copies of the gene (recessive)
-Recessively inherited mutations can predispose to cancer → only need one more “hit” instead of two (e.g. familial retinoblastoma where Rb is mutated)
-Two hits needed for non-familial cancers
Describe the different repair mechanisms?
Summary of Oncogenesis (not a question)
What is Metaplasia?
-Metaplasia is the reversible replacement of one mature cell type by another (often in the transition zone).
-Squamous metaplasia → replacement of mucus-secreting columnar epithelium with non-keratinised, stratified squamous epithelium
Examples → cervix, bronchus of smokers
-Intestinal/glandular metaplasia → replacement of squamous epithelium with columnar epithelium
Examples → Barrett’s oesophagus
What is Neoplasia?
-Neoplasia is a state of autonomous cell division (i.e. cell proliferation in the absence of any continuing stimulus). Neoplasms are also called tumours.
-It is a clonal proliferation → originates from a single cell that has acquired specific mutations that allow it to proliferate unchecked
-Neoplasms may be benign or malignant (= cancer)
Describe gradings of tumours?
-Grade 1 (low grade)- cancer cells look like normal cells and are growing slowly
-Grade 2 (intermediate grade)- cells don’t look like normal cells, may be growing more quickly than normal
-Grade 3 (high grade)- cells look very abnormal and growing rapidly
What is the TNM system staging of breast cancer?
-T (tumour)- how big is the tumour?
-N (nodes)- has it spread to one or more lymph nodes?
-M (metastases)- has it metastasised?
-Also have hormone profiling to classify tumours and tailor treatment
-Some tumours express certain genes/ receptors which can be -targeted by drugs
-Herceptin (trastuzumab) targets HER2 oncogene in HER2-positive tumours, block oncogene-> slows growth
-Tamoxifen targets oestrogen receptors in breast tumours which stimulate growth of the tumour (is an ER antagonist in breast tissue)
-Nb: each type of cancer has its own staging system but generally follow TNM model (except blood cancers)
-X in TNM means cannot be assessed/ unknown eg Nx
How does cancer spread?
-Directly into adjacent tissues
-Through lymphatic system
-Through blood vessels
-Along nerves
Describe different cancer types and their cell type
Types of epithelium
Squamous: On the outside of body and areas connected with the outside eg vagina
Cuboidal : Ducts and glands
Columnar: Can have cilia!- resp tract, fallopian tubes/ Non ciliated- GI tract
Transitional/ urothelium: Places exposed to urine- bladder, ureters, urethra
What type of management is avaliable for breast cancer?
