powerpoint

1. Limitless replicative
potential
Gnanika R
2nd year MBBS

2. Synopsis
Introduction
Factors
Examples
Conclusion
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3. Introduction
Normal cells have limited replicative potential
and have regulatory process that leads to
cell death.
All cancers contain cells that are immortal
and have limitless replicative potential.
3

4. FACTORS
 Evasion of
senescence
 Evasion of
mitotic crisis
 Self renewal
capacity

5. Evasion of senescence
Normal cell Cancer cell
• Capacity to divide 60-70 times
• Accumulates DNA damage over
time
• Upregulation by p53 and INK4a
• Reach senescence
• Limitless capacity to divide
• Acquired genetic and epigenetic
aberrations
• Not regulated
• Bypass senescence
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6. Evasion of mitotic crisis
• Mitotic crisis has been ascribed to progressive
shortening of telomeres special DNA sequence
at the ends of the chromosomes that bind several
types of protective protein complexes.
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Cells
divide
Telomeres
shorten
Apoptosis
NORMAL CELL

7. Evasion of mitotic crisis
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8. Evasion of mitotic crisis
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9. Evasion of mitotic crisis
• In cells with dysfunctional p53, Nonhomologous
end-joining pathway (NHEJ) is activated.
• This cycle on repetition eventually produces
mitotic crisis and cell death
• In 85% to 95% of tumours it is due to the
expression of telomerase, the remaining use other
mechanisms that depends on DNA recombination.
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Dysfunctional
p53
NHEJ
Pathway
Cell
death

10. Evasion of mitotic crisis
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11. Self renewal
• Self renewal means that each time a stem cell divides at least one of
the two daughter cells remains a stem cell.
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Symmetrical division 2 stem cells (embryogenesis)
Asymmetrical division 1 stem cell + 1 normal cell which
undergoes apoptosis
• Example: formed elements of bone marrow and blood, epithelial
cells of GIT and skin
• Tumours too must contain cells that self-renew cancer stem cells.

12. Self renewal
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• Cancer stem cells arise from both
the transformation of tissue stem
cell and from the conversion of
conventional somatic cells to
transformed cells with the acquired
property of “stemness”.
• Example: Chronic myeloid
leukemia (CML) and acute
promyelocytic leukemia.

13. Conclusion
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• Cancers can repopulate their stem cell pools from non-stem cell
populations, further complicating efforts to precisely define and
selectively target cancer stem cells.
• Cancer stem cells also have high intrinsic resistance to
conventional therapies due to a low rate of cell division and the
expression of factors like multiple drug resistance-1(MDR1) that
counteract the effects of chemotherapeutic drugs

14. Thank you
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