PBL Week 10 Flashcards
What is the biochemistry of the different checkpoints of the cell cycle?
Cell cycle goes G1 - S - G2 - Mitosis. Some cells move from G1 to G0, where no more division takes place; for example, in nerve cells. There are 2 checkpoints which regulate the cell cycle - one at the end of G1 and one at the end of G2. There are 2 proteins that regulate these; cyclins and cyclin-dependant kinases (CDK). The cyclin-dependant kinases add phosphate groups onto other proteins/enzymes, activating or deactivating them. The kinases are themsevles activated by specific cyclins, which are created at specific points in the cell cycle. This allows a cell to determine if a phase is working; the checkpoints can only be passed when the specific cyclins are made.
P53 is a protein that inhibits CDK and blocks cell cycle progression. It is made from tumour supressor genes which, if defective, can lead to cancer (over half of tumours have a defect in p53). This is because the cell cycle must have checkpoints and blocking proteins so that the cell doesn’t continually divide and instead go through all the phases; this unregulated division is what forms tumours.
What is the role of receptors and cell signalling in the cell cycle?
Many growth factors bind to receptors on the cell surface, stimulating cells to progress through the cell cycle and divide. Several of these receptors are kinsases that phosphorylate other proteins and genes when binding to a ligand, activating or deactivating them, altering the progression of the cell cycle.
What is molecular basis of cancer?
Tumour supressor genes are those that have a halting effect on the cell cycle or cause apoptosis. 2 types: DNA repair genes recognise DNA damage and either repair or initiate apoptosis and cell cycle repressors suppress the genes and proteins that cause the coninuation of the cell cycle. P53 is an example of a cell cycle repressor.
Oncogenes are genes that code for proteins that direct cell growth, potentially uncontrollably. They form from proto-oncogenes, which code for proteins that regulate cell growth and differentiation. These proteins are involved in signal transduction and the execution of mitogenic (causes mitosis) signals.
Proto-oncogenes can turn into oncogenes through: Deletion/point mutuation - happens in the gene or in a regulatory protein, can lead to overexpressed proteins.
Gene amplication/mRNA stability - mRNA stays in the cell for longer, leads to overexpressed proteins.
Chromosomal rearrangement - involves translocation of a gene to a nearby regulatory sequence, leading to overexpressed proteins.
How does a tumour form and how can cancer cells spread to other parts of the body?
Cell ususally stop growing due to contact inhibition and initiate apoptosis when they detect an error within the cell. However, if a mutation stops apoptosis from occurring, forming a cluster of mutated cells called a neoplasm/tumour. If the cell grows at the same speed of neighbouring cells and stays in one place, it’s considered benign. If it develops a mutation that causes it to grow quickly and become invasive (spreading to other cells) it is considered malignant or cancerous. The rapid growth can lead to further mutation. If a piece of the tumour cell breaks off and spreads to another part of the body, the cell has metastasised.
What are the different types of cell death and how are they related to tumour cells?
3 types of cell death: Apoptosis is programmed cell death, occurring for homeostatic reasons. Autophagy is also programmed usually occurs due to nutrient deficiency reasons and involves the creation of large vacuoles that eat away at the cell. Finally, necrosis happens due to external factors, causing the cell to die.
Tumour cells occur when a mutation stops apoptosis from occurring, leading to uncontrolled growth.
What is the role of the histopathology department in the diagnostic biopsy and excision of breast cancer?
After a mammogram (2 views, cradiocaudal and mediolateral, taken of each breast) reveals an abnormal lump, an ultrasound is taken to assess the tumour size and determine if the cancer has spread to the lymph nodes, where it usually spreads to first. The patient then has an ultrasound-guided biopsy, where a needle is inserted into the breast to take a sample of the cancerous tissue. After being placed in formulin (to prevent it from breaking down) and encasing in molten paraffin (to take thin sections of the biopsy). These are then analysed under a microscope and a report is generated, which contains all the information about the tumour and therefore how it can be treated.
After receiving the report, the treatment can then be created for the patient. The standard treatment for a breast carcinoma is a wide excision that aims to remove the tissue with a good margin of normal tissue. At the same time, a sentinel lymph node biopsy is carried out to determine if it has spread to the lymph nodes or not. Then, radiotherapy is done on the tumour bed to prevent reoccurence. The removed tumour is dyed to preserve the orientation and encased in paraffin. The different margins of the tumour are then tested to confirm that no tumour cells were left behind and that there is no chance of reoccurence. The size and size of the margins is included in a seperate report, furthermore a computer algorithm (PREDICT model) is used to determine the risk of reoccurence, using the different traits of the cancer. Depending on the cancer, chemotherapy can be used (for high grade tumours and for reducing the risk of systemic reoccurence).
What is included in a tumour report created by the histopathology department and how is it relevant to the patient’s treatment?
The report contains 6 things:
Tumour type - an example is “invasive ductal carcinoma of no special type”. Carcinoma means a cancer originating in the cells of the skin or tissue lining organs (in this case, breast tissue). Tumours that originate from glands are called invasive adenocarcinoma, of which invasive ductal carcinomas are a type that originate in milk ducts of the breast. Special type tumours are rarer.
Tumour grade - refers to how closely the tumour resembles the tissue it comes from; high grade tumours grow quicker, are more agressive and are more likely to spread. An example is “tumour grade of 3 (T3, P3, M3)”. T stands for how well tubules are forming (tubules), P stands for how large and variable the nuclei is compared to regular cells (nuclear pleomorphism) and M stands for how rapidly the cells are dividing (mitotic rate). The higher the grade, the lower the survival.
In-situ component - refers to if the tumour is invasive or not. An in-situ carcinoma means that the cancer is not invasive and is still benign, however the grade (can be low, intermediate or high) is a measure for how long it will take for the cancer to become invasive/malignant (e.g 5 years for a low grade ductal carcinoma in situ compared to 15 years for a high grade).
Vascular invasion - refers to if the tumour has spread to the lymphatics or venous channels, making it more likely to spread to other areas. Vascular invasion could be a sign of metastasis.
Oestrogen receptors - oestrogen is a driver of breast cancer growth when the carcinoma has oestrogen receptors. The quick score refers to how strongly the tumour expresses these receptors, with a max score of 8.
Her 2 - stands for human epidermal growth factor receptors, which area family of 4 surface receptors that transmit signals relating to cell growth. When overexpressed, Her 2 leads to stronger cell signalling, leading to increased reponsive to growth factors. Scored on a scale of 0 - 3+; 0-1+ is negative for Her 2, 2+ is boderline, 3+ is positive.
How do current treatment options for cancer target cancer cells?
Certain drugs can target receptors on cancer cells, slowing or stopping their growth. For example, Tomoxifen block oestrogen receptors in breast carcinomas.
Surgery and radiotherapy are both used in local areas to remove or destroy cancer cells. In order to avoid damaging regular cells during radiotherapy, shaped radiation beams are aimed from several angles of exposure to intersect at the tumour, giving it a much larger absorbed dose than the surrounding tissues.
Chemotherapy targets cancer cells by using a mixture of drugs that target rapidly dividing cells to destroy the cell or stop mitosis from occurring. As a side effect, the chemotherapy also targets other rapidly-dividing cells, such as cells in bone marrow, the digestive tract and hair follicles.
Why are cancer rates on the rise and what is the doctor’s role in cancer prevention?
Cancer rates are on the rise due to an aging population (cancer rates increase with age, as body becomes less effective at filtering out errors), obesity (causes many types of cancer), smoking (is the largest form of preventable cancer), UV rays (suns rays can cause skin cancer without protection) and more.
Doctors can encourage patients to maintain a healthy lifestyle and BMI, encourage patients to stop smoking and protect themselves while in the sun. They can also educate patients on the risks involved with these. Furthermore, GPs can invite those deemed vulnerable in for regular cancer screenings, e.g regular mammograms in females or prostate exams in males.
