Cancer Cell Division Gone Wrong Mutations Cell division

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Cancer: Cell Division Gone Wrong

Cancer: Cell Division Gone Wrong

Mutations

Mutations

Cell division is regulated by both positive and negative signals. Positive signals start the

Cell division is regulated by both positive and negative signals. Positive signals start the process of cell division. Negative signals inhibit cell division.

CB 12. 13

CB 12. 13

Cancer: • is the loss of control over cell division. • Tumors are normal

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.

GO! STOP! cancer CB 19. 13

GO! STOP! cancer CB 19. 13

How do these incorrect signals arise? Multiple mutations are required for a single cell

How do these incorrect signals arise? Multiple mutations are required for a single cell to become cancerous. CB 19. 14

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

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

Causes of mutations: • Replication errors – Exacerbated by poor DNA repair • Other

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

Causes of mutations: • Replication errors – Exacerbated by poor DNA repair • Other

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

Change in the US Death Rates* by Cause, 1950 & 2000 Rate Per 100,

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

2003 Estimated US Cancer Cases* Men 675, 300 Women 658, 800 32% Breast Prostate

2003 Estimated US Cancer Cases* Men 675, 300 Women 658, 800 32% Breast Prostate 33% Lung & bronchus 14% Colon & rectum 11% Urinary bladder 6% 6% Uterine corpus Melanoma of skin 4% 4% Ovary 4% Non-Hodgkin lymphoma 3% Melanoma of skin 3% Thyroid 2% Pancreas 2% Urinary bladder Non-Hodgkin lymphoma 4% Kidney 3% Oral Cavity 3% Leukemia 3% Pancreas 2% All Other Sites 17% 12% Lung & bronchus 11% Colon & rectum 20% All Other Sites *Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder. Source: American Cancer Society, 2003.

2003 Estimated US Cancer Deaths* Lung & bronchus 31% Prostate 10% Colon & rectum

2003 Estimated US Cancer Deaths* Lung & bronchus 31% Prostate 10% Colon & rectum 10% Men 285, 900 Women 270, 600 25% Lung & bronchus 15% Breast 11% Colon & rectum Pancreas 5% 6% Pancreas Non-Hodgkin lymphoma 4% 5% Ovary Leukemia 4% 4% Non-Hodgkin lymphoma Esophagus 4% 4% Leukemia Liver/intrahepatic bile duct 3% 3% Uterine corpus Urinary bladder 3% 2% Brain/ONS Kidney 3% 2% Multiple myeloma All other sites 22% 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.

Change in the US Death Rates* by Cause, 1950 & 2000 Rate Per 100,

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

Cancer Death Rates*, for Men, US, 19301999 Rate Per 100, 000 Lung Stomach Prostate

Cancer Death Rates*, for Men, US, 19301999 Rate Per 100, 000 Lung Stomach Prostate Colon and rectum Pancreas Leukemia Liver *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.

Cancer Death Rates*, for Women, US, 1930 -1999 Rate Per 100, 000 Lung Uterus

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.

Tobacco Use in the US, 1900 -1999 Male lung cancer death rate Per capita

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.

Tobacco Use in the US, 1900 -1999 Male lung cancer death rate Per capita

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.

Causes of mutations: • Replication errors –Exacerbated by poor DNA repair • Other biological

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

Treating cancer: • Avoid it – Avoid mutagens – DNA repair gets less efficient

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

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

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

Our immune system protects us from cancer T-cells recognize and eliminate abnormal cells; such

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

Treating cancer: • Avoid it – Avoid mutagens – DNA repair gets less efficient

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

Treating cancer: • Avoid it – Avoid mutagens – DNA repair gets less efficient

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

Treating cancer: • Avoid it – Avoid mutagens – DNA repair gets less efficient

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

Treating cancer: • Avoid it – Avoid mutagens – DNA repair gets less efficient

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

Chemotherapy n xi To X X a rapidly dividing cell

Chemotherapy n xi To X X a rapidly dividing cell

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

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

Some cancers over-express MDR toxin MDR MDR xi To toxin MDR MDR MDR toxin

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