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Principles of oncology Carcinogenesis Is the process whereby external influence causes cancer. Classified to: 1.Initiation in which the cells undergo transformation to a premalignant stage. 2.Promotion in which these cells are induced to form a cancer. The agents which causes cancer are termed carcinogens. 1.Chemical carcinogens, eg : tobacco causing lung cancer, Asbestos causing pleural cancer, Alcohol causing ca. esophagus. 2.Physical carcinogens eg: Uv. Light causing skin cancer , X-ray damaging bone marrow. 3.Viruses eg: papilloma virus causing CX. Cancer , E.B virus causing Burkitt’s Lymphoma. 4.Diet eg: heavily cooked meat is rich in hetero cyclic Amine which is a potent carcinogen , on contrary high vegetable intake is associated with low rate of cancer, both vegetables and fruits are rich in anti-oxidants , they have protective effect. 5.Obesity increases risk of cancer , exercise decreases risk of cancer explained by caloric restriction decrease the rate of cellular division. Molecular genetics of cancer Tumor genesis is a multi-step process the genes which are known to play a vital role are two major categories. 1.Onco genes they promotes cell –growth and proliferation if activated can disturb the regulations of many intracellular path ways leading to cancer,eg: K-ras leading to colorectal cancer. 2.tumour-suppressor genes in contrast to onco genes if .inactivated they will lead to cancer. Inherited cancer syndromes 1.Approximatly 1% of all cancer pt. 2.Mostly due to inactivation of T.S.G. 3.Although uncommon it is of great clinical and scientific importance. 4.Off springs can have genetic counseling and screening. 5.Examples F.A.P familial adenomatous polyposis. The kinetics of tumours The tumour is composed of : 1.The growth fraction; these cells which are actively dividing. 2.The clonogenic fraction : cells which are not proliferating but obtain to do so under appropriate stimuli . 3.End cell fraction : cells which have no capacity to divide and so will die. Cell death As in normal tissue the commonest form of cell death in tumour is by apoptosis this physiological process involves a series of steps which consists of condensation and fragmentation of chromatin and sub sequent shrinkage of the cell. Cell remnant is taken by macrophage without involving an inflammatory reaction. The other sort of cell death is by necrosis which does involve an inflammatory reaction. There is a balance in normal tissue between cell loss and cell proliferation . In the tumour either the cell proliferation is more than normal or cell death is slower than normal. Cell cycle We have five stages in the cell cycle ,G1 ,S,G2,M,and Go. M:- mitosis G1:- gap phase S:- synthesis , DNA replication G2:- 2nd gap phase Go:-resting or clonogenic cells Gompertzian curve 1.Small tu. Grow rapidly large tu. Grow slowly because of decrease in blood supply . 2.Small tu. Have large growth fraction , large tu. Have small G.F. 3.Small tu. More sensitive to C.T and R.T. Invasion and metastases Is the ability of the tu. To invade locally or to distant organs. Causes : 1.Increased pressure caused by rapidly dividing cells . 2.Lack of cell to cell adhesion. 3.Increased motility of malignant cells caused by some onco genes. 4.Proteolytic enzymes enables cancer cells to pass through basement membrane.