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Cancer
 Diagnosed each year in one in every 250 men and one in
every 300 women(WHO).
 Clonal in origin
Six hallmarks
1. Immortality eg. HeLa cells
2. Produces GO signal, ie proto-oncogenic protiens
3. Override STOP signals (TSGs inactivation)
4. Resist cell death
5. Angiogenesis
6. Metastasis
Treatments available
 Radiotherapy
 Chemotherapy
 Hormone therapy
 Cytokines
 Monoclonal antibodies
 Gene therapy
Gives rise to all type of cells
present in an organism. E.g.,
embryonic stem cells derived from
blastocyst
INDUCED PLURIPOTENCY
iPSCs were first produced in
2006 from mouse epidermal
fibroblast cells
In 2007, iPSCs were derived
from human cells by Shinya
Yamanaka's team at Kyoto
University, Japan
Nobel Prize in Physiology or
Medicine for the discovery that
mature cells can be
reprogrammed to become
pluripotent
Mouse iPSCs
Human iPSCs
Takahashi and Yamanaka, Cell, Aug 25, 2006
iPSc Generation
Potentials of iPS cellsPotentials of iPS cells
 Ability to differentiate into many cell types
 Easily accessible
 Individual-specific i.e. personalized or non-immunogenic
 Vastly renewable
 Useful for studying mechanisms of disease
 Useful for drug, toxicity testing
Application of the hiPSCs
Application in cancer
Disease modeling
Immuno therapy
Immunotherapy
• Immune system fails to effectively fight
the tumor.
Tumor tolerence
Weak response
Defending property
• autologous immune enhancement
Dendritic cell vaccines(iPSDCs)
T-cell therapies
NK-cell therapies
Contd…..
• Antitumor monoclonal
antibodies
block growth signals
stops angiogenesis
Drug/radiation delivery
• Cancer vaccines
Disease modeling
• Best model to study cancer pathogenesis is primary patient
sample.
• iPSCs can be generated from cancer cells.
• Can use for
Pancreatic Ductal Adenocarcinoma(PDAC)
Chronic myeloid Leukemia(CML)
Juvenile Mylomonocytic Leukemia(JMML)
Obstacles in therapeutic
application of iPSCs in humans
• Use of harmful oncogenes as part of the reprogramming
factors.
• Use of viral vectors for gene delivery that carry the risk of
insertional mutagenesis.
• Low efficiency and slow kinetics of reprogramming.
• Lack of robust and reliable differentiation protocols for human
iPS cells
Conclusion
• Discovery of iPSC is a remarkable boost to research and
therapy
• Offered a new field for cancer research and future possible
applications in the clinical practice.
• use of hiPSCs may contribute to the development of future
personalized cell therapies and open new possibilities
References
1. Seung-Ick Oh, Chang Kyu Lee, Kyung Jin Cho,Kyung-Ok
Lee, Ssang-Goo Cho, and Sunghoi Hong; Technological
Progress in Generation of Induced Pluripotent Stem Cells
for Clinical Applications, The Scientific World Journal ,10
(2012),1-10
2. MartinezMatthias Stadtfeld and Konrad Hochedlinger;
Induced pluripotency: history, mechanisms and
applications, Genes & Development, 24 (2010), 2239–
2263
3. Timothy J Nelson, Almudena , Fernandez,
SatsukiYamada,Yasuhiro Ikeda, Carmen Perez-Terzic,
Andre Terzic; Induced pluripotent stem cells: advances
to applications, Stem Cells and Cloning: Advances and
Applications,3 (2010), 29-37
4. Eamon Geoghegan and Lucy Byrnes; Mouse induced
pluripotent stem cells, The International Journal of
Developmental Biology, 52, (2008), 1015-1022
5. Kazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi
Narita,Tomoko Ichisaka, Kiichiro Tomoda and Shinya
Yamanaka; Induction of Pluripotent Stem Cells from Adult
Human Fibroblasts by Defined Factors,Cell, 131, (2007), 1–
12
human induced pluripotent stem cells in cancer treatment

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human induced pluripotent stem cells in cancer treatment

  • 1.
  • 2. Cancer  Diagnosed each year in one in every 250 men and one in every 300 women(WHO).  Clonal in origin
  • 3. Six hallmarks 1. Immortality eg. HeLa cells 2. Produces GO signal, ie proto-oncogenic protiens 3. Override STOP signals (TSGs inactivation) 4. Resist cell death 5. Angiogenesis 6. Metastasis
  • 4. Treatments available  Radiotherapy  Chemotherapy  Hormone therapy  Cytokines  Monoclonal antibodies  Gene therapy
  • 5. Gives rise to all type of cells present in an organism. E.g., embryonic stem cells derived from blastocyst
  • 7. iPSCs were first produced in 2006 from mouse epidermal fibroblast cells In 2007, iPSCs were derived from human cells by Shinya Yamanaka's team at Kyoto University, Japan Nobel Prize in Physiology or Medicine for the discovery that mature cells can be reprogrammed to become pluripotent Mouse iPSCs Human iPSCs
  • 8. Takahashi and Yamanaka, Cell, Aug 25, 2006
  • 10. Potentials of iPS cellsPotentials of iPS cells  Ability to differentiate into many cell types  Easily accessible  Individual-specific i.e. personalized or non-immunogenic  Vastly renewable  Useful for studying mechanisms of disease  Useful for drug, toxicity testing
  • 12. Application in cancer Disease modeling Immuno therapy
  • 13. Immunotherapy • Immune system fails to effectively fight the tumor. Tumor tolerence Weak response Defending property • autologous immune enhancement Dendritic cell vaccines(iPSDCs) T-cell therapies NK-cell therapies
  • 14. Contd….. • Antitumor monoclonal antibodies block growth signals stops angiogenesis Drug/radiation delivery • Cancer vaccines
  • 15. Disease modeling • Best model to study cancer pathogenesis is primary patient sample. • iPSCs can be generated from cancer cells. • Can use for Pancreatic Ductal Adenocarcinoma(PDAC) Chronic myeloid Leukemia(CML) Juvenile Mylomonocytic Leukemia(JMML)
  • 16. Obstacles in therapeutic application of iPSCs in humans • Use of harmful oncogenes as part of the reprogramming factors. • Use of viral vectors for gene delivery that carry the risk of insertional mutagenesis. • Low efficiency and slow kinetics of reprogramming. • Lack of robust and reliable differentiation protocols for human iPS cells
  • 17. Conclusion • Discovery of iPSC is a remarkable boost to research and therapy • Offered a new field for cancer research and future possible applications in the clinical practice. • use of hiPSCs may contribute to the development of future personalized cell therapies and open new possibilities
  • 18. References 1. Seung-Ick Oh, Chang Kyu Lee, Kyung Jin Cho,Kyung-Ok Lee, Ssang-Goo Cho, and Sunghoi Hong; Technological Progress in Generation of Induced Pluripotent Stem Cells for Clinical Applications, The Scientific World Journal ,10 (2012),1-10 2. MartinezMatthias Stadtfeld and Konrad Hochedlinger; Induced pluripotency: history, mechanisms and applications, Genes & Development, 24 (2010), 2239– 2263 3. Timothy J Nelson, Almudena , Fernandez, SatsukiYamada,Yasuhiro Ikeda, Carmen Perez-Terzic, Andre Terzic; Induced pluripotent stem cells: advances to applications, Stem Cells and Cloning: Advances and Applications,3 (2010), 29-37
  • 19. 4. Eamon Geoghegan and Lucy Byrnes; Mouse induced pluripotent stem cells, The International Journal of Developmental Biology, 52, (2008), 1015-1022 5. Kazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi Narita,Tomoko Ichisaka, Kiichiro Tomoda and Shinya Yamanaka; Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors,Cell, 131, (2007), 1– 12