Cancer: Cell Division Gone Wrong

1. Cancer: Cell Division Gone Wrong

2. Mutations

3. Cell division is regulated by bothpositive and negative signals.Positive signals start the processof cell division.Negative signals inhibit cell division.

4. CB 12.13

5. Cancer: • is the loss of control over cell division. • Tumors are normal cells that are dividing inappropriately. • They stop performing their “normal” function, and are dividing repeatedly.

6. GO! STOP! cancer CB 19.13

7. How do these incorrect signals arise? Multiple mutations are required for a single cell to become cancerous. CB 19.14

8. Causes of mutations: • Replication errors • Exacerbated by poor DNA repair

9. Causes of mutations: • Replication errors • Exacerbated by poor DNA repair • Other biological agents • Viruses • Transposons

10. Causes of mutations: • Replication errors • Exacerbated by poor DNA repair • Other biological agents • Viruses • Transposons • Environmental factors • Ultraviolet light • Mutagenic chemicals • smoking, industrial waste, natural toxins

11. Change in the US Death Rates* by Cause, 1950 & 2000 Rate Per 100,000 1950 2000 Cancer HeartDiseases Pneumonia/Influenza CerebrovascularDiseases * Age-adjusted to the 2000 US standard population. Source: US Mortality Volume 1950, National Vital Statistics Report, 2002, Vol. 50, No. 15.

12. 2003 Estimated US Cancer Cases* Men675,300 Women658,800 32% Breast 12% Lung & bronchus 11% Colon & rectum 6% Uterine corpus 4% Ovary 4% Non-Hodgkin lymphoma 3% Melanoma of skin 3% Thyroid 2% Pancreas 2% Urinary bladder 20% All Other Sites Prostate 33% Lung & bronchus 14% Colon & rectum 11% Urinary bladder 6% Melanoma of skin 4% Non-Hodgkin lymphoma 4% Kidney 3% Oral Cavity 3% Leukemia 3% Pancreas 2% All Other Sites 17% *Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder. Source: American Cancer Society, 2003.

13. 2003 Estimated US Cancer Deaths* Men285,900 Women270,600 Lung & bronchus 31% Prostate 10% Colon & rectum 10% Pancreas 5% Non-Hodgkin 4%lymphoma Leukemia 4% Esophagus 4% Liver/intrahepatic 3%bile duct Urinary bladder 3% Kidney 3% All other sites 22% 25% Lung & bronchus 15% Breast 11% Colon & rectum 6% Pancreas 5% Ovary 4% Non-Hodgkin lymphoma 4% Leukemia 3% Uterine corpus 2% Brain/ONS 2% Multiple myeloma 23% All other sites ONS=Other nervous system. *Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder. Source: American Cancer Society, 2003.

14. Change in the US Death Rates* by Cause, 1950 & 2000 Rate Per 100,000 1950 2000 Cancer HeartDiseases Pneumonia/Influenza CerebrovascularDiseases * Age-adjusted to the 2000 US standard population. Source: US Mortality Volume 1950, National Vital Statistics Report, 2002, Vol. 50, No. 15.

15. Cancer Death Rates*, for Men, US, 1930-1999 Rate Per 100,000 Lung Stomach Prostate Colon and rectum Pancreas Liver Leukemia *Age-adjusted to the 2000 US standard population. Source: US Mortality Public Use Data Tapes 1960-1999, US Mortality Volumes 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2002.

16. Cancer Death Rates*, for Women, US, 1930-1999 Rate Per 100,000 Lung Uterus Breast Colon and rectum Stomach Ovary Pancreas *Age-adjusted to the 2000 US standard population. Source: US Mortality Public Use Data Tapes 1960-1999, US Mortality Volumes 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2002.

17. Tobacco Use in the US, 1900-1999 Male lung cancer death rate Per capita cigarette consumption Female lung cancer death rate *Age-adjusted to 2000 US standard population. Source: Death rates: US Mortality Public Use Tapes, 1960-1999, US Mortality Volumes, 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2001. Cigarette consumption: Us Department of Agriculture, 1900-1999.

19. Tobacco Use in the US, 1900-1999 Male lung cancer death rate Per capita cigarette consumption Female lung cancer death rate *Age-adjusted to 2000 US standard population. Source: Death rates: US Mortality Public Use Tapes, 1960-1999, US Mortality Volumes, 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2001. Cigarette consumption: Us Department of Agriculture, 1900-1999.

20. Causes of mutations: • Replication errors • Exacerbated by poor DNA repair • Other biological agents • Viruses • Transposons • Environmental factors • Ultraviolet light • Mutagenic chemicals • smoking, industrial waste, natural toxins

21. Treating cancer: • Avoid it • Avoid mutagens • DNA repair gets less efficient as we age

22. Environment plays a large role in the chance of contracting cancer.

23. Our immune system protects us from cancer T-cells recognize and eliminate abnormal cells; such as cells with many mutations

24. Treating cancer: • Avoid it • Avoid mutagens • DNA repair gets less efficient as we age • Surgery • Must remove all cancer cells • Non-invasive

25. Treating cancer: • Avoid it • Avoid mutagens • DNA repair gets less efficient as we age • Surgery • Must remove all cancer cells • Non-invasive • Radiation • Directed at tumor; causes DNA damage -> cellular self-destruction • Mutagenic, side effects

26. Treating cancer: • Avoid it • Avoid mutagens • DNA repair gets less efficient as we age • Surgery • Must remove all cancer cells • Non-invasive • Radiation • Directed at tumor • Mutagenic, side effects • Chemotherapy • Toxins directed at rapidly dividing cells • Mutagenic, many side effects

27. Treating cancer: • Avoid it • Avoid mutagens • DNA repair gets less efficient as we age • Surgery • Must remove all cancer cells • Non-invasive • Radiation • Directed at tumor • Mutagenic, side effects • Chemotherapy • Toxins directed at rapidly dividing cells • Mutagenic, many side effects

28. Chemotherapy Toxin X X a rapidly dividing cell

29. Normal Multi-Drug Resistance protein toxin/hormone/etc MDR toxin/hormone/etc toxin/hormone/etc MDR MDR MDR toxin/hormone/etc

30. Some cancers over-express MDR toxin toxin toxin toxin Toxin MDR MDR MDR MDR I’m a cancer cell with over-expressing MDR. I laugh at your toxins. MDR toxin toxin MDR toxin MDR toxin MDR MDR MDR MDR MDR toxin toxin toxin toxin