16. Characteristics of Neoplasms Differentiation and Anaplasia Rate of Growth Invasion of Surrounding Tissue Metastatic Potential
17. Differentiation and Anaplasia Differentiation: How similar tumor cells are to normal cells Benign Tumors: Well-differentiated Malignant Tumors: Range of differentiation Anaplasia: The lack of differentiation
59. Epidemiology Second most common cause of death In the United States, one in five deaths is due to cancer In Pakistan, . . . .
60. Most Common Cancers Men Prostate Lung Colorectal Women Breast Lung Colorectal
61. Cancer Mortality Trends Decreased deaths in men from Ca Lung: Decreased smoking Prostate: PSA screening Ca Colon: Colonoscopy screening Decreased deaths in women from Ca Breast: Self exam, Mammography Ca Cervix: Pap Smear
62. Cancer Mortality Trends Increased deaths in men and women from Hepatocellular Ca: Hepatitis C Increased deaths in women: Ca Lung: Smoking
71. Inherited Cancer Syndromes Person inherits one autosomal dominant mutant gene Carriers of the mutated gene have a significantly increased risk of developing cancer Familial Adenomatous Polyposis Retinoblastoma
72. Defective DNA Repair Autosomal recessive Cells have decreased ability to recover from DNA damage Xeroderma pigmentosum Ataxia-Telangiectasia
73. Familial Cancers Clustering of certain cancers in families Early age at onset Two or more first-degree relatives with the same cancer Siblings: 2-3 X risk of cancer Multiple / Bilateral tumors Multiple low-penetrance genes
83. Growth Factors Normal: Paracrine stimulation Cancer cells: Synthesize the same growth factors to which they are responsive (Autocrine loop)
84. Growth Factor Receptors Normal: Receptors are transiently activated Mutated: Constitutive activation without the need for Growth Factor binding!
85. Signal Transducing Proteins Located on inner surface of plasma membrane Receive signals from Growth Factor Receptor Transmit signals to the cell nucleus Two most important members of this group: RAS ABL
86.
87. RAS Most commonly mutated oncogene One of a family of small GTP/GDP binding Proteins Normal activation is transient Upon Activation, GDP is replaced by GTP GTP is hydrolyzed to GDP by intrinsic GTPase GTPase activity is accelerated by GTPase- Activating Proteins
88. RAS Point mutations interfere with hydrolysis of GTP RAS is trapped in the activated state Cell ends up in a state of continuous proliferation
90. BCR-ABL Translocation ABL proto-oncogene: Limited tyrosine kinase activity Localizes to nucleus and promotes apoptosis in cells with DNA damage BCR-ABL Hybrid Protein: Much higher, uncontrolled tyrosine kinase activity Can’t move into nucleus, thus can’t cause apoptosis in cells with damaged DNA Chronic Myeloid Leukemia
93. Transcription Factors MYC proto-oncogene: Induced rapidly upon signal to divide Activate CDK’s Inhibits CDKI’s Levels decline to baseline when cell cycle begins
94. Transcription Factors Mutated MYC oncogene: Persistent expression / overexpression Leading to sustained proliferation
96. Cell Cycle Regulators Cyclins D, E, A and B appear sequentially and bind to various CDK’s Cyclin-CDK complexes drive the cell through the cel cycle CDKI’s exert negative control over the cell cycle
