a) w/c 6-Jan-14 Tumours/Repro Flashcards
p53 is an example of what type of gene?
Both p53 and Rb protein are examples of TUMOUR SUPRESSOR GENES (BRAKE ANAOLOGY).
For suppresion to be stopped, need both copies to be mutated/deleted
White haired cats are suspectible to which type of UV radiation induced cancer?
Squamous cell carcinoma (ear tips, nose)
The opposite of tumour supppressor genes are known as_____
mitogens Stimulate cell proliferation.
Aka proto-oncogenes e.g. Ras/Raf
5 hallmarks of cancer
- Resisting cell death
- Sustaining proliferative signalling
- Inducing angiogenesis
- Enabliing replicative immortaility
- Evading growth suppressors
- Activating invasion and metastasis
Two types of cancer boxers are predisposed to
Lymphoma and mast cell tumours = boxers are a walking neoplasm.
German shepherd dogs: haemangiosarcoma
3 ways cancer cells can undergon uncontrolled proliferation
- Secretion of endogenous growth receptors
- Mutation of growth factor receptors. Constitutively activate in absence of growth factor. e.g. canine mast cell tumour KIT mutation
- Mutation of intraceullar signalling molecules. Activating proto-oncogenes e.g. Ras/Raf
Rb protein transduces growth-inhibitory signals that originate largely _____
Rb protein OUTSIDE the cell. Determines whether or not the cell cycle progresses
p53, another tumour suppresor gene recieves input from ___ mechanisms
Intracellular mechanisms, if cell viability is suboptimal it calls a halt to cell cycle progression
Can Rb and p53 trigger apoptosis via the caspace cascade? If so, which pathway is involved?
ONLY P53 can trigger APOPTOSIS via the INTRINSIC PATHWAY leading to CASPASE cascade (i.e. intracellular)
What is the significance of the Bcl-2 family in oncogenesis?
Cancer cells need to resist cell death. Regulated cell death has two mechanisms. Intrinsic and Extrinsic pathway.
Cancer cells can downregulate death receptors or UPREGULATE Bcl-2 family which blocks the INTRINSIC pathway
How can tumour cells avoid the EXTRINSIC pathway of cell death?
Cancers can downregulate the death receptors on the cell surface (i.e. extrinsic pathway)
c.f. with intrinsic pathway –> p53 intracellularly. Cancer cells can UPREGULATE Bcl-2 family
Which specialised DNA polymerase is upregulated in cancer cells to enable replicative immortality?
Normal cells undergo cellular senescence due to shorted telomeres (protect end of chromosomes)
Cancer cells contained DNA polymerase Telomerase which adds telomere repeat segments = immortality
Why do tumour cells need to induce angiogenesis? How do they do this?
Once a tumour reaches a critical size, is at risk of hypoxia-induced cellular necrosis therefore requires a blood supply.
SECRETE ANGIOGENIC FACTORS such as Vascular Endothelial Growth Factor (VEGF).
Faciliates metastasis/ Haematogenious spread
What do CARCINOMA cells use to metastasise?
Loss of E-cadherin by carcinoma cells allows them to detach from primary tumour and spread.
- Local drainage LN
- Liver
- Lungs
- Bone Marrow
Significance of tumour-promoting inflammation?
Some tumours demonstrate a significant infiltration of inflammatory cells. Although its an attempt to eradicate it can be COUNTERPRODUCTIVE.
Inflammatatory cells can supply bioactive molecules e.g. growth factors, immunosuppressive mediators
DDx for cancer tumour?
Abscess (systemically ill? pyrexia?), grauloma, haematoma, seroma, cyst
How could a haematoma be differentiated from a tumour?
Painful? Hot? Fluid-filled? Well-defined or ill-define? Fixed to under lying tissue?
What steps should be undertaken when a tumour is identifed?
Cytotoly (fine needle aspirate), no negative pressure to start with, evaculate syreinge using air.
Why is Histopathology preferred to cytology?
Histopathology: Tissue- Gives information on cell type and morphology/ tissue architecqture
Cytology: Cells
Both cytology and histopathology can both examines cell morphology for signs of malignancy (mitotic index, megakaroyocyte)
A fast growing tumour is more likely to be ____
malignant than a slow growing tumour.
Benign tumours grow by expansion
Malignant tumours grow more rapidly and disrupt surrounding tissues
Difference between tumour GRADE and STAGE?
Grade: Assigned by the PATHOLOGIST. low, intermediate or high grade
Stage: Assigned by the clinician. EXTENT of the disease in the patient. Use the TNM system
What is the TNM system?
T: Primary tumour: Size, mobility, relationship to surrounding tissue
N: Node: Assess the drainage LN (can be internal)
M: Distant metastasis. Imaging inc CT.
Most common site for metastasis in small animals?
Lungs. Can present with dyspnoea/ cough
X-ray, inflated radiograph, ideally 3
A tumour 3-5cm in diameter would have which TNM grade/
T2
WHO system for staging canine lymphoma. Stage III is when….
Generalised lymph node involvement (both sides of diaphram)
If the liver is involved in canine lymphoma, the WHO classifcation is stage
IV
V: bone marrow/ blood/ other organ systems
(substage a= systemic signs, b= no ss)
Which canine tumour is TNM most commonly used>
Canine mammary tumours
When treating an anal sac carcinoma, what is it important to check for?
Paraneoplastic effect of tumour. DUE TO TUMOUR PRODUCTION OF PTH. Present with hypercalcemia, if untreated = Renal damage
Which other tumours have paraneoplastic effects?
Hypercalcemia? lymphoma, myeloma, lymphoid leukaemia, other carcinomas, thymoma
Hypoglycaemia: Insulinoma
Hyperglobulinema: Myeloma (gamma globulin)
Why can mast cell tumours present with gastric ulceration/ vomiting?
Canine mast cell tumours = histamine release, can also have gastrin secreting tumours
Define Eutocia?
Normal parturition
What happens is Stage 1 of parturition?
Positioning of the foetus for birth, dilation of cervix, exposure of foetus membranes through the vulva
How long should stage 2 last in the COW vs the MARE?
Cow: 0.5-4 hours for stage 2 (expulsion of calf)
Mare: 20 minutes- 30 minutes (expulsion of foal)
MUCH SHORTER.
Also Stage 3 (fetal membranes) much shorted in mare 1-2 hours. 6 hours for COW
Which breed of horse are most likely to have dystocia?
10% of draught breeds have dystocia incidence vs 1-2% of ponies.
Higher in beef than dairy
Why should the water bag not be popped?
The allantochorion provides tension/ pressure to help feedback mechanisms that result in stage 2 of parturition (expulsion of fetus)
The bursting of the bag removes this tension
How can the time at which cows CALVE (time of day) be manipulated?
Cows calve when QUIET
If feed during day–> calve at night
If feed during night –> calve during day
Which presentation is most likely to result in dystocia due to undilated cervic?
Backward presentation, no tapered pressure that the head normally provides.
Manually dilate the vulva, check umbilical cord.
Relative traction forces
- that cow provides=
- that 1 person provides=
- that calving jack provides=
Cow: 70 kg
1 Person: 75kg
Calving jack: 400kg
How do you determine if there is sufficient space in the pelvis for calving?
Hand fits on top of head in pelvis. STRAIGHT LEGS (make sure they don't cross)
A calf should fit if carpal joint is __cm outside cow.
Once head is out, what needs to be done?
carpal joints 10cm outside cow.
Once head is born, ROTATE 90 degrees for hips
When does HIP BLOCK occur?
If following birth of head, calf is not rotated 90 degrees.
to ensure the hips line up in OVAL pelvis . After rotation pull dorsally rather than downwards (as before)
Traction for a caudal presentation should be directed
Dorsally (same as following rotation in normal birth)
When a cow is calving in a longitudinal posterior presentation, what is the critical point?
i.e. backwards
10cm of hock outside vulva. Once get to this point have to deliver quickly by pulling dorsally; umbilical cord will break when head still inside
Difference between early embryonic loss and late embryonic loss?
Early: before maternal regognition (i.e. will cycle normally)
Late: After meteral recognition.
When does pregnancy loss be termed as foetal loss rather than embro loss?
Embryo loss: before day 42
Foetal loss: After day 42 (most mortality before this day)
The majority of early embryo loss is due to…
STRESS/ Environmental/ Genetic factors
NOT DUE TO INFECTIOUS AGENTS