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Neoplasia

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Neoplasia

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  1. Neoplasia Cancer

  2. Cancer A Disorder of Altered Cell Differentiation and Growth = Neoplasia (new growth)

  3. Cancer • The second leading cause of death in the United States • Estimated 1.45 million diagnosed • 559,650 died • 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. 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 duplicated • Duplicated chromosomes are appropriately aligned for distribution between two genetically identical daughter cells • Process of specialization

  5. 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.

  6. 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

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

  8. 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.

  9. 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

  10. Tumor Suppressor Genes • Tumor suppressor genes inhibit the proliferation of cells in a tumor • Inactivate genes and get unregulated growth

  11. 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 • Genetic lesions that render the pRB pathway non-functional are thought to occur in almost all human cancers

  12. 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

  13. 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

  14. p53 • Acquired mutation in p53 is the most common genetic alteration found in human cancer • One p53 allele may be deleted while the other is mutated • Therapies are directed at re-establishing the p53 genes to cause massive apoptosis of cancer cells

  15. Telomerase • DNA polymerase can’t replicate the ends of chromosomes • Ends of chromosomes called telomeres • Telomeres • 15 to 20 kilobase pairs long • Cut off with each cell division • If pRB and p53 are nonfunctional, cells bypass non-growth function to become cancerous • Cancer cells can reactivate Telomerase

  16. Oncogene • A gene that has the potential to cause cancer • Activated oncogenes can cause cells that ought to die to survive and proliferate instead

  17. Proto-oncogenes • A normal gene that can become an oncogene due to mutations or increased expression • Proto-oncogenes code for proteins that help to regulate cell growth and differentiation. • Proto-oncogenes are often involved in signal transduction

  18. Types of Proto-Oncogenes • Examples of proto-oncogenes • RAS andMYC

  19. Genetic Events Leading to Oncogene Formation • Ras proto-oncogene family • Signal relaying proteins that transmit growth signals to the nucleus • Ras communicates signals from outside the cell to the nucleus • Mutations in ras genes can permanently activate it and cause inappropriate transmission inside the cell, even in the absence of extracellular signals • These signals result in cell growth and division, dyregulatedras signaling can ultimately lead to oncogenesis and cancer

  20. Genetic Events Leading to Oncogene Formation • Myc proto-oncogene • Encodes for growth signal proteins • Myc (c-Myc) codes for a transcription factor that is located on chromosome 8 in humans is believed to regulate expression of 15% of all genes • A mutated version of Myc is found in many cancers • Myc to be persistently expressed. This leads to the unregulated expression of many genes some of which are involved in cell proliferation and results in the formation of cancer

  21. 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

  22. Genetic and Molecular Basis of Cancer • Epigenetic factors • http://youtu.be/Xjq5eEslJhw • http://youtu.be/wFsxVkuChdU

  23. Neoplasia • Growth is uncoordinated and relatively autonomous • Lacks normal regulatory controls over cell growth and division • Tends to increase in size and grow after stimulus ceases or needs of organism are met

  24. BENIGN VERSUS MALIGNANT TUMORS Benign Tumors Do not penetrate (invade) adjacent tissue borders Do no spread (metastasize) to different sites. Malignant Tumors Invades contiguous tissues Metastasizes to distant sites Takes up residence, grows anew and invades again

  25. BENIGN VERSUS MALIGNANT TUMORS • BENIGN • Malignant tumors kill • Benign tumors don’t kill (mostly) • Benign intracranial tumor in the meninges (meningioma) can kill by exerting pressure on the brain • Benign mesenchymal tumor of the left atrium (myxoma) can kill by blocking the orifice of the mitral valve

  26. Benign Tumors • The primary descriptor of any tumor, benign or malignant is its cell or tissue of origin. • Bening tumors are identified by the suffix “oma” which is preceded by reference to the cell or tissue of origin • Chondroma, resembles chondrocytes • Epithelioma, tumor of squamous cells • Adenoma, arising from glandular epithelium such as in the colon or endocrine glands

  27. Normal Cartilage

  28. Benign Chondroma

  29. Benign Thyroid Adenoma

  30. Hemartoma of the Lung

  31. Malignant Tumors • Malignant tumors usually carry the same name, except the suffix “carcinoma” is applied to epithelial cancers and “sarcoma” to mesenchymal cancers • Gastric adenocarcinoma • Malignant tumor of the stomach • Squamous cell carcinoma • An invasive tumor of the skin • Transitional cell carcinoma • Malignant neoplasm of the bladder

  32. Squamous cell Carcinoma of the Skin

  33. Historically Important • Hepatoma of the liver, Melanoma of the skin, Seminoma of the tesis, Lymphoma or lymphoproliferation tumor are all highly malignant • “emia” – relationship with the blood • Leukemia

  34. Histologic Diagnosis of Benign Tumors • Benign tumors in general resemble their parent tissues both histologically and cytologically • The lining epithelium may resemble that of the normal tissue • May be surrounded by a connective tissue capsule (or not)

  35. Histologic Diagnosis of Malignant Tumors • Malignant tumors depart from the parent tissue morphologically and functionally • Anaplasia or cellular atypical • Lack of differentiated features in a cancer cell • The degree of anaplasia correlates with the aggressiveness of the tumor • MitotisActvity • Invasion • Metastases

  36. Anaplasia • 1. Variation in the size and shape of cells and cell nuclei (pleomorphism • 2. Enlarged and hyperchromatic nuclei with coarsely clumped chromatin and prominent nucleoli • 3. Atypical mitoses • 4. Bizarre cells

  37. Mitotic Activity • Abundant mitoses are characteristic of many malignant tumors but are not a necessary criterion

  38. Invasion • Invasion, particularly of blood vessels and lymphatics

  39. Metastases • The presence of metastases identifies a tumor as malignant

  40. Definitions • Neoplasia • uncontrolled growth of cells that is not under physiologic control. • Tumor or "mass lesion” • a "growth" or "enlargement" which may not be neoplastic (such as a granuloma). • Cancer • implies malignancy • neoplasms can be subclassified as either benign or malignant.

  41. Tumor • A swelling that can be caused by a number of conditions • Inflammation • Trauma • Mass of cells that arises because of overgrowth

  42. Tumors • Named by adding the suffix -oma to the parenchymal tissue type from which the growth originated

  43. Types of Tumors • Adenoma:benign tumor of glandular epithelial tissue • Adenocarcinoma:malignant tumor of glandular epithelial tissue • Carcinoma:malignant tumor of epithelial tissue • Osteoma:benign tumor of bone tissue • Sarcoma:malignant tumors of mesenchymal origin • Papilloma:benign microscopic or macroscopic fingerlike projection growing on a surface

  44. Tissue evidence of carcinogenic factors at work • The two forms of cellular transformation that are potentially reversible, but may be steps toward a neoplasm, are: • Metaplasia: the exchange of normal epithelium for another type of epithelium. • Metaplasia is reversible when the stimulus for it is taken away. • Dysplasia: a disordered growth and maturation of an epithelium, which is still reversible if the factors driving it are eliminated.