neoplasia n.
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  1. Neoplasia Cancer

  2. Neoplasia A Disorder of Altered Cell Differentiation and Growth

  3. Cancer • The second leading cause of death in the United States • Estimated 1.45 million diagnosed • 559,650 die each year • Prostate is the most common cancer for men • Breast is the most common cancer for women • Excluding skin cancer • Lung cancer is the leading cause of death in both men and women

  4. Definitions • Benign – not capable of metastasizing and usually not capable of causing death • Malignant – capable of metastasizing and capable of causing death • Neoplasm – an uncontrolled growth of new cells, benign or malignant • Tumor – literally, a mass; however, in everyday language, a neoplasm • Cancer – any kind of malignant neoplasm • Carcinoma – a malignant neoplasm of epithelial cells • Sarcoma – a malignant neoplasm of mesenchymal cells

  5. Growth Layers

  6. More Definitions • -oma is used for benign tumors • There is a matching malignant variety for every benign variety • For example, adenoma – aden = gland and oma = swelling • A benign tumor of fibrous tissue is a fibroma

  7. Even More Definitions • Malignant tumors are named by adding carcinoma if the tumor is of epithelial origin • Breast duct epithelium, prostate epithelium, bronchial epithelium and so on • Sarcoma if the tumor is from mesenchymal tissue • Bone, cartilage, fat, muscle or fibrous tissue • Adenocarcinoma if the tumor is of glandular epithelial cells • Fibrosarcoma if the tumor

  8. Mutations • The root cause of all cancer is damaged (mutant) DNA • This causes the normal cycle of cellular reproduction to go awry

  9. Cell Cycle • Cell proliferation • Process of cell division • Inherent adaptive mechanism for replacing body cells • Sequence of events that occurs as a cell duplicates • Genetic information is also duplicated • Duplicated chromosomes are appropriately aligned for distribution between two genetically identical daughter cells • Process of specialization


  11. Interphase • G1 (gap 1) • From the end of the M phase until the beginning of DNA synthesis • Growth Phase • The cell determines its readiness to commit to DNA synthesis • S (DNA Synthesis) • DNA replication • G2 (gap 2) • DNA replication is assessed and errors are corrected • the gap between DNA synthesis and mitosis, the cell will continue to grow.

  12. Cell Cycle • M-Phase (Mitotic Phase) • The replicated chromosomes are separated and packaged into two new nuclei by mitosis • The cytoplasm is divided between the two daughter cells by cytokinesis • Prophase • Metaphase • Anaphase • Telophase


  14. Cyclins and CDK’s • Two key classes of regulatory proteins, Cyclinsand Cylin-Dependent Kinases (CDKs), determine a cell’s progress through the cell’s cycle

  15. Cell Cycle • Cyclins are proteins that control the entry and progression of cells through the cell cycle • Cyclins bind to cyclin-dependent kinases (CDK), which are enzymes that phosphorylate proteins • Cyclin-dependent kinase inhibitors-regulates cell cycle checkpoints to prevent DNA replication mistakes.

  16. Cyclins and CDK’s • Progression from one phase of the cell cycle to the next is controlled by the orderly activation of cyclin dependent kinases • Cyclin proteins bind to CDK’s to cause phosphorylation and activation


  18. Cell Growth Control Genes • All cells contain genes that function as “go” or “stop” switches (restrains cell growth) • The “go” genes are proto-oncogenes • Proto-oncogenes produce growth-promoting proteins that stimulate normal cell division • Oncogenes (cancer genes) come from mutations of proto-oncogenes • Their function is to stimulate uncontrolled cellular division

  19. Tumor Suppressor Genes • “stop” genes are the opposite of proto-oncogenes • Called Tumor suppressor genes • Produce proteins that inhibit cell division • Mutation of tumor suppressor genes leaves cell growth uninhibited


  21. Tumor Suppressor Genes • Retinoblastoma is a rare childhood cancer due to the inactivation of a specific tumor suppressor gene • Retinoblastoma (pRB) gene • Prevents cell division • Retinoblastoma tumor suppressor protein (pRB) • Phosphorylation of pRB causes progression of the cell into the S-phase • A point mutation renders the pRB pathway non-functional • Thought to occur in almost all human cancers

  22. Tumor Suppressor Genes • p53 gene • Found on the small arm of chromosome 17 • Its protein product is in virtually all normal tissues • Controls p53 protein levels • p53 proteins increase with damage to DNA • Initiates apoptosis of DNA-damaged cells

  23. p53 Gene • “Guardian of the genome” • Restricts uncontrolled cellular proliferation under circumstances in which cells with abnormal DNA might propagate • Deleted or mutated in 70% to 80% of cases of colorectal cancer, breast cancer, small cell carcinoma of the lung, hepatocellular carcinoma, astrocytoma and numerous other tumors

  24. Epigenetics • Involves changes of gene expression without a change in the DNA • “silence” genes such as tumor suppressor genes • Methylation of the promoter region • Prevents transcription to cause gene inactivity • Can be inherited

  25. Genetic and Molecular Basis of Cancer • Epigenetic factors • •

  26. The Spread of Neoplasms • Direct invasion and extension • Seeding of cancer cells in body cavities • Metastases

  27. Premalignant States and Conditions • Neoplasms evolve over time from normal tissue • Dysplasia • A pre-malignant state of tissue that is atypical and clearly abnormal but not yet malignant • Dysplasia does NOT always progress to malignancy • Carcinoma in situ • Cancer that never metastasizes

  28. Invasion • Cancer is latin for crablike • Cancer grows by sending crablike projections into the surrounding tissues • Cancers secrete enzymes to break down proteins to increase invasion and penetration of surrounding tissues • Prevents sharp demarcation for surgical removal

  29. Seeding • A tumor erodes and shed cells into body cavities • Peritoneal, pleural, pericardial cavity and joint spaces • Floating in body space from one surface to another • These cancers grow in masses and secrete fluids • Ascites, pleural effusion

  30. Metastasis • The ability to skip from one place to another • Via lymphatics or the bloodstream • Breast via lymphatics to lymph nodes • Via blood to bone • Metastases may occur by seeding

  31. Metastasis

  32. Nourishment of Tumors • Angiogenesis • Neoplasms develop their own blood supply

  33. Liver Metastasis

  34. Human Papilloma Virus • Infection in the cervix • Causes dysplasia, carcinoma in situ and invasive carcinoma • Takes many years and repeated infections to produce dysplasia or malignancy

  35. Grading and Staging of Malignancies • Cancer Grading • Microscopic assessment of the degree of differentiation, atypia and other features of malignancy • Cancer Staging • Evaluation of behavior by assessing size of the primary tumor and its spread • Assessed by physical exam, history and pathologic and diagnostic imaging