Cancers of the GIT Flashcards
what are the hallmarks of cancer?
Evasion of apoptosis Self sufficiency in growth signals Insensitivity to anti growth signals Tissue invasion and metastasis Limitless replicative potential Sustained angiogenesis
What are the two types of oesophageal cancer?
SCC - Squamous cell carcinoma
ADC - Adenocarcinoma
What is the survival chance of oesophageal cancer?
8% 5 year survival
What are the risk factors for ADC?
Barrettts metaplasia
about a 0.5% conversion rate from BM to lead to ADC
10% of GORD patients have BM
What are the risk factors for Oesophageal adenocarcinoma?
Gender Age Reflux LOS relaxing drugs Obesity
Helicobacter-pylori (less likely to develop ADC when present)
Fruit and Veg
Anti-oxidants
What is an important cause for hypergastrinaemia and duodenal ulcers in the antrum?
Helicobacter Pylori
Prevents the stomach from making acid but causes inflammation leading to the production of gastric ulcers
What is a major cause for Gastritis?
Helicobacter pylori
How is Hp treated?
Triple therapy consisting of antibiotics amoxicillin and clarithromycin and a proton pump inhibitor
How does Hp evolve to colonise the stomach?
Expresses Urease - neutralising gastric acid
Expresses Mucinase - allowing the bacteria to drill into the mucous layer and therefore cause mucosal injury
Expresses Adhesion receptors allowing the bacteria to bind to cells
Expresses exotoxins causing mucosal damage
What is the cause of Hereditary diffuse-type gastric carcinoma (HDGC)?
germline mutation in CDH1 gene which encodes for E-cadherin
How does a CDH1 mutations lead to cancer?
Abrasion in E-cadherin and therefore leads to cells becoming more motile as they are not adhered to their neighbours. This leads to metastasis and hence can lead to the cells invading new tissues and hence cause cancer.
Why is E-cadherin negative more likely to cause cancer?
More likely for cells to become motile and metastasise
Therefore more likely for cells to invade other tissues
Therefore lead to cancers
What causes E-cadherin repression?
Epigenetic events
Promoter Hypermethylation (silencing of genes)
EMT regulators
What are the main EMT regulators?
Snail and slug
They suppress expression of E-cadherin and instead induce factors associated with mesenchymal transition.
What induces snail and slug expression and why is this important?
If we know what induces them then we can prevent their expression leading to EMT and furthermore cancer..
FGF, Wnt, BMP, TGF-beta
What are some risk factors associated with colorectal cancer?
Disease of the aged
Meat and fish
Obesity
Lack of physical activity
What is the incidence of colorectal cancer?
40,000 per year
What is the mortality rate of colorectal cancer?
19,000 per year
What is the survival rate of Colorectal cancer?
50%
What geographical correlation is related to colorectal cancer?
Associated with western lifestyle
40% of patients may have colorectal cancer prevented if they had adopted a better lifestyle
What are the types of colorectal cancer?
Sporadic - 80-90%
Familial - 10%
What are the 2 main types of Familial colorectal cancer?
FAP - Familial adenomatous polyposis
HNPCC (leech syndrome) -
What is a treatment for FAP?
Colectomy
What is the tumour suppressor for FAP?
ACP - adenomatous polyposis coli
How does APC work?
When the APC is lost it leads to FAP.
Beta catenin can enter cells and induce oncogenes
APC is involved in the mechanism in regulation of Beta catenin.
GSK-3beta phosphorylates Beta catenin leading to its degradation.
Why does a patient with a mutation in APC lead to FAP?
Mutant APC cannot be phosphorylate and degrade Beta-catenin and therefore it is able to enter the nucleus and induce oncogenes leading to cancer.
How do sporadic colorectal cancers develop?
Through Adenoma carcinoma sequences
How does the adenoma carcinoma sequence lead to cancer?
APC is randomly mutated and this may lead to genomic instability and thus more alterations in other alleles can be caused and hence lead to metastasis and cancers.
How is the 5 year survival rate of colorectal cancer being improved?
By the development of an Asymptomatic screening program.
Looking for diseased individuals without symptoms and therefore find disease early and hence should be more curable.
How does the screening program work?
Over the ages of 60 are sent a stool smear test kit and where they send off stool to be examined for blood to see if they have disease.
What is a surveillance program?
Where disease has been Identified and the patients are now being monitored for other disease.
What is personalised medicine?
Tailored treatment of a disease to an individual to ensure that the persons treatment is responsive.
How is personalised medicine being produced?
Tumours removed are genomically sequenced to therefore be tested to see which drugs they respond to and hence are able to therefore tailor new medicines to people with similar genomical tumours.
