0602 - Pathophysiology of solid tumour development - EG Flashcards
Define neoplasm
An abnormal mass of tissue growth which exceed and is uncoordinated with that of normal tissues and persists in the same excessive manner after the cessation of the stimuli which evoked it.
List the factors for tumour development (8).
(1) self-sufficiency in growth signals (oncogenes). (2) insensitivity to growth inhibitory signals (tumour suppressor genes). (3) evasion of apoptosis. (4) limitless replicative potential (telomerase). (5) sustained angiogenesis. (6) ability to invade (proteases). (7) ability to metastasise. (8) defective DNA repair.
What monitors the G2 restriction checkpoint and what is it monitoring?
monitored by “the guardian of the genome” p53. The checkpoint makes sure that the DNA replication of S phase was conducted with fidelity before mitosis occurs. Prevents abhorrent division, as if DNA infidelity occurred in S will initiate apoptosis.
What is monitored at the G1 restriction checkpoint?
The decision of whether the cell should begin S phase to copy information and later divide, or if theis should be delayed, or if the cell should enter a resting stage.
What is the limited ability of a cell to divide known as?
Hayflick limit. roughly 50-70 divisions are able for a non-stem cell, this is due to and affected by the activity of telomerase to lengthen the telomeres on chromosomes.
What tumour has one of the fastest replicating rates?
breast tumour with an approximate doubling time of 30 days.
What is the rough doubling time of a tumour once it becomes clinically apparent?
about 2-3 months
What 3 factors determine the rate of tumour growth?
(1) doubling time of tumour cells. (2) the fraction of cells in the replicative pool. (3) the rate of cell loss from the growing tumour.
What is the growth fraction of a tumour?
The proportion of cells within the tumour population that are in the proliferative pool. By the time a tumour is clinically detectable the majority of cells are not in the replicative pool = Low Growth Fraction. Varies 5-20% with rapidly growing tumours about 20%.
What are some reasons that cells leave the proliferative pool?
shedding, lack of nutrients, apoptosis, differentiation, reversion of G0.
Is chemotherapy more effective on tumours with high or low growth fraction? What affect can radiation have?
High growth fraction. radiation can push cells from G0 phase to G1 phase and thus become susceptible to treatment.
What are the steps that enable malignant cells to invade other tissues?
(1) tumor cells loose their adhesion molecules. (2) detach (3) attach to basement membrane matrix components (4) degrade ECM by production of proteolytic enzymes (5) migration of tumour cells.
Describe the four steps in epithelial to mesenchymal transition.
(1) tumour induces hypoxic and inflammatory response in surrounding tissue. (2) normal tissue induces EMT in the tumour. (3) EMT produces cancer stem cell traits. (4) cancer stem cell with invasion and metastatic spread.
List some common sites and symptoms of cancer metastasis.
Brain: headaches, seizures, vertigo. Respiratory: cough, hemoptysis, dyspnea. Lymph: lympatenopathy. Liver: hepatomegaly, jaundice. Skeletal: pain, fractures, spinal cord compression.
What are the 2 phases of a metastatic cascade?
(1) invasion of extracellular matrix, require enzymatic degradation of ECM by proteolytic enzymes such as collagenase. (2) vascular (veins>lymph and arteries) dissemination and homing of tumour cells.
