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Pt. IV: Cancer Initiation, Promotion, and Progression

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Pt. IV: Cancer Initiation, Promotion, and Progression

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    1. Pt. IV: Cancer Initiation, Promotion, and Progression

    2. Percival Pott & Chimney Sweeps 1775. Made the connection environmental toxins? scrotal cancer.

    3. Two-stage model of Cancer Development 1. Initiators: Mutagens (compounds that reacts with and cause mutations in DNA) that predispose cells to develop tumors 2. Promoters: Non-reactive compounds that stimulate tumor development ‘Complete Carcinogen’: a compound that can act as both an Initiator (mutagen) & Promoter

    4. Progression of Cancer Stepwise transformation of a benign tumor to a neoplasm and to malignancy Associated with a karyotypic change (aneuploid) Changes in growth rate, invasiveness, metastasis and an alteration in biochemistry and morphology

    5. Stages of Tumor Development I. Hyperplasia (Benign Tumor): The mutated cell keeps dividing leading to an excess of cells. They are still normal but there are too many of them! ie: Uterine Fibroid, Skin Mole II. Dysplasia (Pre-Malignant): More mutations lead to increasingly abnormal growth. The cells & tissue no longer look or act normal. ie: Abnormal PAP smear

    6. Stages of Tumor Development (con’t) III. Severe Dysplasia or Carcinoma in situ Additional mutations make the cells and tissues even more abnormal. Cells 'regress' / de-differentiated. But still contained within the initial location & have not spread. Often curable by surgery.

    7. Stages of Tumor Development (con’t) IV. Cancer (Malignant tumors): invade surrounding tissues and/or spread (metastasize) to areas outside the local tissue

    8. Angiogenesis The development of blood vessels is an essential step in the growth of a tumor Otherwise tumors cannot grow larger than a fraction of an inch When cells in a tumor get too far from a blood vessel, the oxygen & nutrient levels drop? Hypoxia This triggers tumor cells to produce angiogenesis factors (VEGF) The tumor 'tricks' the body into creating new blood vessels

    9. Angiogenesis as a Drug Target Surgeons observed that surgical removal of a large primary tumor led to the rapid development of metastatic growths This suggested that the primary tumor was producing some Tumor Inhibitor that kept small metastatic growths from progressing. When the large tumor was removed, the smaller tumors were free to grow. Endostatin—is currently in clinical trials as a cancer therapy

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