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A Presentation From the American Cancer Society

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1 A Presentation From the American Cancer Society
Cancer Statistics 2005 A Presentation From the American Cancer Society The American Cancer Society presents Cancer Statistics 2005. ©2005, American Cancer Society, Inc.

2 US Mortality, 2002 No. of deaths % of all deaths Rank Cause of Death
1. Heart Diseases 696, 2. Cancer , 3. Cerebrovascular diseases 162, 4. Chronic lower respiratory diseases 124, 5. Accidents (Unintentional injuries) 106, 6. Diabetes mellitus 73, 7. Influenza and pneumonia 65, 8. Alzheimer disease 58, 9. Nephritis 40, 10. Septicemia 33, Cancer accounts for nearly one-quarter of deaths in the United States, exceeded only by heart diseases. In 2002, there were 557,271 cancer deaths in the US. Source: US Mortality Public Use Data Tape 2002, National Center for Health Statistics, Centers for Disease Control and Prevention, 2004.

3 Change in the US Death Rates* by Cause, 1950 & 2002
Rate Per 100,000 1950 2002 Compared to the rate in 1950, the cancer death rate was about the same in 2002, while rates for other major chronic diseases decreased during this period. Heart Diseases Cerebrovascular Diseases Pneumonia/ Influenza Cancer * Age-adjusted to 2000 US standard population. Sources: 1950 Mortality Data - CDC/NCHS, NVSS, Mortality Revised. 2002 Mortality Data: US Mortality Public Use Data Tape, 2002, NCHS, Centers for Disease Control and Prevention, 2004

4 The Hallmarks of Cancer
Hanahan and Weinberg, Cell 100:57-70 (2000)

5 Cell Regulatory Networks Important in Cancer Cells
Hanahan and Weinberg, Cell 100:57-70 (2000)

6 The Cell Cycle START or Restriction Point

7 The Main Jobs of the Cell Cycle:
To accurately transmit the genetic information! To maintain normal ploidy; i.e. diploidy! Euploidy: additions of whole chromosome sets e.g. n, 2n, 3n, 4n = haploid, diploid, triploid, tetraploid Aneuploidy: additions or subtractions of one or more single chromosomes e.g. 2n + 1, 2n -1, 2n + 2, etc.

8 Properties Required for Transmission of
Chromosomes During Cell Division 1. One and only one centromere 2. Functional telomere at both ends 3. Chromosomes must be fully replicated 4. Chromosomes cannot be too large or too small

9 S Phase of the Cell Cycle

10 Mitosis

11 Fibroblasts in Culture
blue = DNA green = microtubules

12 Mitosis in an Early Fruit Fly Embryo

13 Anaphase in a plant cell

14 Metaphase in a mammalian cell

15

16 G1-S and G2-M are the major control points in the cell cycle
Fuse M phase cell with interphase cell: Interphase nucleus enters M Fuse S phase cell with G1 cell: The G1 nucleus enters S phase Fuse S phase cell with G2 cell: The G2 nucleus does not enter S phase Rao and Johnson cell fusion experiments

17 Cyclin Dependent Kinases Regulate the Cell Cycle

18 Experimental Systems Important for Cell Cycle Studies
Saccharomyces cerevisiae Arbacia punctulata Schizosaccharomyces pombe Xenopus laevis

19 Fission yeast: Schizosaccharomyces pombe

20 Budding Yeast Saccharomyces cerevisiae

21 Isolating Temperature Sensitive Mutants in Haploid Yeast

22 Cdc Mutants Arrest at the Same Cell Cycle Phase
Permissive (low) temperature Restrictive (high) temperature

23 Phosphorylation of CDK Targets Changes Their Activity
Now performs a cell cycle function

24 The Behavior of a Temperature Sensitive cdc Mutant
cdc mutant growing at permissive temp (23C) cdc mutant growth arrested after 6 hrs at non-permissive temp (36C)

25 How to Clone cdc Genes in Yeast

26 Cdc Genes Encode Proteins Needed for DNA Replication
Studies in S. cerevisiae

27 Cdc Genes Encode Proteins Needed for the G2-M Transition:
Studies in S. pombe cdc2+ encodes a kinase Moreover = cdc28 in S. cerevisiae!

28 Cyclin was Discovered in Sea Urchin Embryos
can stimulate to lay lots of eggs Protein Level Time cyclin A cyclin B M

29 (Spisula is actually a clam.)
mitosis (Spisula is actually a clam.)

30 Overview of the frog life cycle
OOCYTE GROWS WITHOUT DIVIDING (MONTHS) FERTILIZED EGG DIVIDES WITHOUT GROWING (HOURS) FERTILIZATION 1 mm sperm tadpole feeds, grows and bcecomes an adult frog

31 The Maturation of Frog Eggs

32 The Maturation of Frog Eggs
An Assay for Maturation Promoting Factor (MPF) Yoshio Masui, 1971

33 MPF Activity Peaks Before Each Cell Division
Moreover, MPF has kinase activity

34

35 Purification of MPF: The Birth of Cyclin Dependent Kinases
This is cdc2+!! (Cdc28 in S. cerevisiae) This is cyclin!! Which = cdc13+ in S. pombe

36 Phosphorylation of CDK Targets Changes Their Activity
Now performs a cell cycle function

37 The Nobel Prize in Physiology or Medicine, 2001
“for their discovery of key regulators of the cell cycle”


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