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A micro-environmental mode of carcinogenesis Xu Zhou Max Planck Institute for Complex Physics SEMINAR "Principles of ...
What causes Cancer? – cellular view <ul><li>Once it was taken as infectious disease </li></ul><ul><li>Genetic disease of m...
What microenvironment is important?  <ul><li>Clone is cell reprogramming by changing microenvironment  </li></ul><ul><li>N...
What causes Cancer?  – Environmental view <ul><li>Tumour microenvironment in driving tumorigenesis depend on somatic genet...
Cancer develops with the change of its microenvironment <ul><li>Cell with oncogene turning on => extra growth => still ben...
Hypothesis of micro-environment selection model <ul><li>There is no cancer programming </li></ul><ul><li>cancer gene mutat...
A warm-up: predator-prey model
Cancer Evolution model (I)  <ul><li>A kinetic model with parameters Start  </li></ul><ul><li>Xi – number of different phen...
Cancer Evolution model (II)  <ul><li>Cancer evolution - proliferation away from base membrane - invasive </li></ul><ul><li...
Evolution barriers vs. Cancer mutations
Tumorigenesis vs. Dynamic system evolutions
The good of the Model <ul><li>A mathematical framework to explain why phenotypes appear in certain pattern  </li></ul><ul>...
What’s bad in the model <ul><li>This is not new derived from this model </li></ul><ul><li>Each phenotype change is trigger...
Conclusions <ul><li>Cancer is caused by genetic mutations and environmental selections </li></ul><ul><li>Cancer developmen...
Some key questions about cancer <ul><li>Multi-cellular disease   </li></ul><ul><li>Sth wrong with coordination of cells </...
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Math Model for Cancer Micro Env Model

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This is a Journal club PPT for a math model for Cancer and its micro-Environment

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Math Model for Cancer Micro Env Model

  1. 1. A micro-environmental mode of carcinogenesis Xu Zhou Max Planck Institute for Complex Physics SEMINAR &quot;Principles of cancer development“, November 10, 2008
  2. 2. What causes Cancer? – cellular view <ul><li>Once it was taken as infectious disease </li></ul><ul><li>Genetic disease of multi-cellular organism - Oncogenes - tumor suppressor genes </li></ul><ul><li>Evolution vs. de-evolution </li></ul>
  3. 3. What microenvironment is important? <ul><li>Clone is cell reprogramming by changing microenvironment </li></ul><ul><li>Normal breast epithelium cells => cancer cell by ECM-degrading enzyme </li></ul><ul><li>Tumour microenvironment’s roles in in tumor development, start in 1960’s, now revived </li></ul>“ The tumour microenvironment—Introduction”, Seminars in Cancer Biology , 12, 2, 87-155, (2002)
  4. 4. What causes Cancer? – Environmental view <ul><li>Tumour microenvironment in driving tumorigenesis depend on somatic genetic alterations? </li></ul><ul><li>Tumour microenvironment is independent from cancer cell gene mutation </li></ul>“ Tumour microenvironment: No changes necessary”, Nature Reviews Cancer   8 , 324 – 325, (2008)
  5. 5. Cancer develops with the change of its microenvironment <ul><li>Cell with oncogene turning on => extra growth => still benign </li></ul><ul><li>Balance with ECM structures destroyed => Cancer </li></ul><ul><li>Cancer stem cells, epithelial-mesenchymal transition, increased angiogenesis and unrestrained cell growth may result from deregulation of tissue microenvironment </li></ul>
  6. 6. Hypothesis of micro-environment selection model <ul><li>There is no cancer programming </li></ul><ul><li>cancer gene mutation under selection pressure of microenvironment </li></ul>Waddinton’s epigenetic landscape
  7. 7. A warm-up: predator-prey model
  8. 8. Cancer Evolution model (I) <ul><li>A kinetic model with parameters Start </li></ul><ul><li>Xi – number of different phenotypes </li></ul><ul><li>Ki – need to contact with base memberane </li></ul>
  9. 9. Cancer Evolution model (II) <ul><li>Cancer evolution - proliferation away from base membrane - invasive </li></ul><ul><li>Evolution dynamics change, leads to different phenotypes </li></ul>
  10. 10. Evolution barriers vs. Cancer mutations
  11. 11. Tumorigenesis vs. Dynamic system evolutions
  12. 12. The good of the Model <ul><li>A mathematical framework to explain why phenotypes appear in certain pattern </li></ul><ul><li>Parameters to associate hallmark of cancer mutations </li></ul><ul><li>Cure cancer by re-engineering its microenvironment </li></ul>
  13. 13. What’s bad in the model <ul><li>This is not new derived from this model </li></ul><ul><li>Each phenotype change is triggered by changing those parameters manually. </li></ul><ul><li>i.e. I know what’s happening, then I put it into the model </li></ul>
  14. 14. Conclusions <ul><li>Cancer is caused by genetic mutations and environmental selections </li></ul><ul><li>Cancer development can be modeled as evolution dynamic system, each phenotype corresponds to a certain evolution advantage in the micro-environment </li></ul><ul><li>Cure cancer by re-engineering its microenvironment </li></ul>
  15. 15. Some key questions about cancer <ul><li>Multi-cellular disease </li></ul><ul><li>Sth wrong with coordination of cells </li></ul><ul><li>Of old age </li></ul>

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