Week 4 Flashcards
How common is colorectal cancer in both men and women ?
- 2nd most common cancer in females in 3rd most common in males.
What is an adenocarcinoma?
Cancer that grows in the epithelial cells of glands.
Where does colorectal cancer develop?
In the GI tract, rectal and colon adenocarcinomas develop in the cells of the lining of the large intestine (crips). They often start in the inner lining and then spread to other layers
Describe the make-up of mucinous adenocarcinomas and how they spread compared with normal adenocarcinomas.
60% made up of mucus. This causes cancer cells to spread more quickly and become more aggressive that normal adenocarcinomas.
Why are mucinous adenocarcinomas hard to treat?
o Mucous layer surrounds cancer – hard to be treated by chemotherapy
Use more intense / aggressive therapy
Where do carcinoid tumours develop and what does this make them?
develop in nerve cells – neuroendocrine cells that help regulate hormone production…. So are neuroendocrine tumours (NETs).
May also develop in the lungs or GI tract.
Where do primary colorectal lymphomas develop?
Develop in the lymphatic system in lymphocytes. Usually in narrow areas such as the lymph nodes, bone marrow, spleen, thymus, and digestive tract.
Where do Gastroinetinal stromal tumours form? And what type of tumour are they classed as and why?
o Form in interstitial cells of Cajal (ICCs) in the GI tract.
o Classified as sarcomas
Cancers that begin in the connective tissues.
What is a Leiomyosarcoma? And Where do they affect?
A sarcoma which is a cancer of the smooth muscle.
Leiomyosarcomas can affect three layers of muscle in the colon and rectum. These muscles usually work together to guide waste through the digestive tract.
Why have incidence rates of adenocarcinomas stayed fairly constant over years?
Incidents rates have stayed fairly constant due to lifestyle factors, eating processed foods and red meats, drinking alcohol, obesity etc.
- These are increasing in recent years.
However, survival rates are positive for colorectal cancer, especially if it is found early.
What % of cancers are considered fully preventable?
55%
What age sees the peak rate of bowel cancer cases and why?
85-89 - The older generation have more time to develop mutations which lead to bowel cancer.
Outline some of the symptoms of colorectal cancer.
Change in bowel habits.
Bleeding from the anus.
Blood in your stool.
abdominal pain.
Loss of appetite.
Persistent lethargy and looking pale or jaundice.
Weight loss
Explain why patients with colorectal cancer may have altered faeces.
o Faces is exceptionally thin due to decrease in the width of the colon.
Why do patients with colorectal cancer experience a loss of appetite and lethargy / jaundice.
Intestines are being compacted so makes the patient feel full.
There may also be a lack of vitamins such as B12 which means insufficient erythrocytes are being produced. This leads to jaundice and anaemia.
Name some of the risk factors for developing colorectal cancer.
Hereditary factors - positive family history.
Modifiable risk factors - smoking, processed meats, alcohol intake, red meat, low intake of vegetables, body fat and obesity.
Name a couple of diseases which increase risk of colorectal cancer.
Long term inflammatory bowel disease.
Diabetes
Explain how eating red meat and processed food increases the risk of getting colorectal cancer.
These food contains lots of nitrates. Nitrates are converted to nitric oxides within the mouth. There nitric oxides react with secondary amines within the body to form n-nitroso compounds.
N-nitroso compounds and carcinogenic and so can cause mutations.
Explain how consuming a westernised diet with high processed foods, red meats and low fibre can cause risk of colorectal cancer.
A lack of fibre means that n-nitroso compounds (formed due to eating too much red) are not moved out of the bowels very quickly and so are in contact with the intestines for a long time. They are then able to cause damage.
Explain how consuming excessive alcohol levels contributes to colorectal cancer.
Oxidative metabolism of alcohol produces acetaldehyde using ADH from the cytosol.
This is couples with the reduction of NAD to NADH.
NADH is then re-oxidised to NAD+ using reactive oxygen species.
CYP2E1 metabolises to acetaldehyde at elevated ethanol (alcohol) concentrations.
Accumulation of reactive oxygen species from alcohol oxidation leads to the formation of lipid peroxides. These cause modifications of proteins and DNA.
Explain how acetaldehyde can cause mutations that can lead to colorectal cancer.
Acetaldehyde is a toxic carcinogen and is broken down to produce lots of reactive oxygen species. If these are in the cells lining to colon for too long, due to build-up, DNA damage is caused.
Explain how lack of fibre in the diet may lead to colorectal cancer.
- Usually acts as a fuel source for ‘helpful’ bacteria which make short chain fatty acids. These protect the intestines by producing mucous. They also ‘switch-off’ inflammation when necessary.
o Fibre also bulks out the faeces to help remove bacteria and toxic material.
In terms of colorectal cancer, explain what happens if inflammation occurs in the GI tract.
The ROS barrier becomes damaged and becomes porus allowing n-nitrosocompounds to reach the intestinal cells and cause mutational changes.
What does ‘NSAIDS’ stand for?
Nonsteroidal anti-inflammatory drug
What current info do we have proving that NSAIDS reduce risk of colorectal cancer?
- Protective medicine that was not originally designed for patients of colorectal cancer. Initially for people with cardiovascular disease.
o Patients on these medicines has a lower incidence of colorectal cancer than those not on the medication.
How is the effectiveness of NSAIDS affected by the inhibitor of COX?
Effectiveness of NSAIDS is contributed to by their potent inhibitor of cyclooxygenase (COX) enzymes. This is because COX-2 expression and prostaglandin E2 synthesis are elevated in CRC.
COX-1 has a low expression in normal human colorectal tissue.
Whereas Cox-2 is elevated in tissue involved in inflammation and cancer.
Explain how COX expression is different in cancerous cells compared with normal cells.
COX-1 has a low expression in normal human colorectal tissue.
Whereas Cox-2 is elevated in tissue involved in inflammation and cancer.
Name the mechanisms by which Aspirin reduces risk of getting colorectal cancer?
- Interrupts nuclear factor kappa B
- Interrupts extracellular signal regulated kinases
- Induces caspase 8 and 9
- Inhibits beta-caetin signalling
Why are patients with cardiovascular disease given aspirin?
This stops COX-2 and prevents thromboxins causing bloodclots via homeostasis.
How is aspirin used to TREAT colorectal cancer?
Aspirin stops PGE2 being formed which is supposed to help aid colorectal cancer given PGE2 causes cell proliferation, angiogenesis, invasion and metastasis.
How do statins inhibit cell growth?
Ras and G-proteins normally progress the cell cycle. Statins lower activation of these within tumour cells and therefore act as an anti-proliferative medication.
How do statins work for treating colorectal cancer in terms of NF Kappa B?
Statins ‘switch off’ NF Kappa B which means reduced migration of cancer cells, no formation of MMP and reduced communication between cancer and stromal cells. This reduced communication prevents more cancerous tissue being formed given cancer uses stromal cells to increase its tissue mass.
From what mechanisms can colorectal cancer arise?
Chromosomal instability.
CpG island methylator phenotype (CIMPs).
Micro-satellite instability
What is chromosomal instability?
Essentially, sister chromatids are not separated evenly within cells. Mis-segregation then leads to a detrimental effect accounting for around 85% of all sporadic CRC cases.
Outline how the CIN pathway works to cause colorectal cancer.
The CIN pathway inactivates mutations in tumour suppressor genes which leads to increase clonal expansion of cells.
This results in loss of heterozygosity and loss of tumour suppressor TP53. This causes expanding cells to have additional growth advantages which ultimately leads to invasive cancers.
What is P53 and what effect would its loss within a genome have?
It is a tumour suppressor gene, so its loss would result in large scale proliferation, de-maturation and inflammation of cancerous cells. Ultimately lack of cellular regulation.
