0602 - Solid Tumor Development - PZ

Question 1

describe the characteristic of neoplasm growth

Answer 1

abnormal mass of tissue growth that exceeds and is uncoordinated with normal tissue.growth persists after cessation of the stimuli which invoked it.

Question 2

what are the 8 ingredients for successful tumor development?

Answer 2

1. self-sufficiency in growth signals (oncogenes)2. insensitivity to growth inhibitors3. evasion of apoptosis4. limitless replication potential5. angiogensis6. invasion capabilities7. ability to metastasise8. defective DNA repair

Question 3

what are the two components of a neoplasm

Answer 3

proliferating cells: determines behaviour and outcome of neoplasmstromal component: responsible for growth and evolution of the neoplasm

Question 4

what are the 4 steps in cell becoming a tumor cell

Answer 4

1. malignant transformation in target cell: bypasses division checkpoints (G1 - whether cell should divide, G2 - checks for DNA damage), divison not controlled or planned.2. proliferation and accumulation: inhibition of apoptosis + telomerase activity.3. local invasion: 4. distant metastasis

Question 5

what are the 3 factors that influence rate of tumour growth, briefly explain what each mean?

Answer 5

1. doubling time of cell - how long is the cell cycle2. amount of cell left in replicative pool - proportion of cells within tumor population that are in proliferative pool, only these cells are capable of mitosis (growth fraction).3. rate of cell loss from pool - cells leave proliferation pool due to: apoptosis, terminal differentiation, shedding, poor nutrition, reversion to G0 (resting phase of mitosis)

Question 6

what are the steps involved in local invasion by tumor cells

Answer 6

1. tumor cells lose their adhesion molecules2. detachment (loosening up of tumor cells)3. attachment to basement membrane matrix4. degradation of basement membrane via enzymes5. migration of tumor cells

Question 7

what are the 2 phases of metastasis, briefly describe each.

Answer 7

1. invasion of ECM - requires active enzyme degradation of ECM components, destruction of matrix leads to creation of path for invasion of tumor cells2. vascular dissemination and homing of tumor cells - aka intravasation, this can occur actively (seeks out vessel) or passively (stumble upon by chance). once cells get into bloodstream, they form tumor cell embolus (by combining with platelets). they migrate “downstream” and goes through the extravasation (same as invasion but going from vessel to tissue). this is followed by angiogenesis to keep the cells alive.

Question 8

define angiogenesis, why is it important in tumor growth.

Answer 8

angiogenesis is the formation of new blood vessel. it is important for tumor growth as without supply of oxygen and nutrients, tumor cells will undergo apoptosis.it also has 3 specific effects:1. delivery of oxygen and nutrients2. newly formed endothelial cells promote growth via growth factor release3. makes it easier for further metastasis

Question 9

how do tumors induced angiogenesis, what are the 2 main tumor associated angiogenic factors?

Answer 9

recruitment of endothelial precursors from bone marrow and inducing existing capillaries to form new capillary buds.the 2 main factors are:1. VEGF - vascular endothelial growth factor2. bFGF basic fibroblast growth factor