Oncology part 2
Table of Contents
Chapter 7: apoptosis ......................................................................................................... 1
Chapter 9: metastasis ..................................................................................................... 11
Chapter 13: infectious agents and cancer ........................................................................ 17
Chapter 10: Angiogenesis ............................................................................................... 24
Chapter 11: nutrients, hormones and gene interaction .................................................... 30
Chapter 12/13 Inflammation, immunotherapy, and cancer .............................................. 35
Chapter 14: technology and drug and diagnostics development ...................................... 46
Keynote lecture 1: proteomics (niet klaar) ....................................................................... 48
Keynote lecture 2: Lung cancer clinic ............................................................................... 51
Keynote lecture 3: quality of life...................................................................................... 56
Keynote lecture 4: MicroRNA from trash to treasure ....................................................... 59
Keynote lecture: molecular imaging ................................................................................ 63
Keynote lecture: functional oncogenomics ...................................................................... 69
Chapter 8: stem cells and differentiation ......................................................................... 74
Chapter 7: apoptosis
General introduction
Definition: apoptosis is the regulated and orderly destruction of a cell through a genetically
encoded process also known as programmed cell death.
Apoptotic process:
- Organized, neat and tidy, leaving behind little evidence of the pre-existing cell
- Cell is removed by macrophages and neighboring cells that recognizes molecular
flags
- Dysregulated during oncogenesis.
Function of apoptosis:
- Active ATP dependent process
- Physiological in many organs:
o Development morphogenesis → tenen aan elkaar
, o Controls cell numbers
o Removal of damaged cells → cellen die dood gaan na in de zon zitten
o Negative and positive selection of lymphocytes
o Cytotoxic effect of radio and chemotherapy
Mitosis per second: 25 miljoen
Apoptosis per second: 25 miljoen
2,2 kg cells per day
Apoptosis vs. Necrosis
Bij de tweede zijn drugs (chemo) gegeven en zie je dat de cellen apoptosis plegen
Apoptosis signalling:
- Induction of apoptosis:
o Programmed
o Loss of growth factors
o Death receptors of the TNFR family
o T and B cell antigen receptors
o CTLs
, o DNA damage
o Stress conditions
- Mitochondrial changes
- Activation of the caspase family
- Proteolytic cleavage of structural and functional proteins
- Induction of apoptosis morphology
Caspases:
- 3 types:
- Initiator: cleaving effector
- Effector: cleave important proteolytic and key
protein of cell
- Inflammatory: neurodegenerative diseases
- 14 family members cloned
- Caspases are cysteine-proteases synthesized as
zymogens
- Requirement for an aspartatic acid at the P1
position
Four apoptosis pathways
- Intrinsic/stress-induced or mitochondrial apoptosis pathway
- Extrinsic/Death receptor mediated apoptosis pathway
- Granzyme B mediated apoptosis pathway
- ER mediated apoptosis pathway
➢ Two major apoptosis pathways
o Apoptosis induced by internal signals: The intrinsic or mitochondrial pathway
o Apoptosis triggered by external signals: The extrinsic or death receptor
pathway
, When Caspase 3,6,7 are cleaved: they are activated: point of no return. They can also
recognize specific sequence on certain proteins that are involved in important processes:
- nuclear lamins
- Cytoskeletal proteins (actin)
- Intermediate filaments (cell structure)
- Specific kinases for cell signaling
- Other enzymes (caspase-activated DNAse)
Extrinsic apoptosis pathway:
Table of Contents
Chapter 7: apoptosis ......................................................................................................... 1
Chapter 9: metastasis ..................................................................................................... 11
Chapter 13: infectious agents and cancer ........................................................................ 17
Chapter 10: Angiogenesis ............................................................................................... 24
Chapter 11: nutrients, hormones and gene interaction .................................................... 30
Chapter 12/13 Inflammation, immunotherapy, and cancer .............................................. 35
Chapter 14: technology and drug and diagnostics development ...................................... 46
Keynote lecture 1: proteomics (niet klaar) ....................................................................... 48
Keynote lecture 2: Lung cancer clinic ............................................................................... 51
Keynote lecture 3: quality of life...................................................................................... 56
Keynote lecture 4: MicroRNA from trash to treasure ....................................................... 59
Keynote lecture: molecular imaging ................................................................................ 63
Keynote lecture: functional oncogenomics ...................................................................... 69
Chapter 8: stem cells and differentiation ......................................................................... 74
Chapter 7: apoptosis
General introduction
Definition: apoptosis is the regulated and orderly destruction of a cell through a genetically
encoded process also known as programmed cell death.
Apoptotic process:
- Organized, neat and tidy, leaving behind little evidence of the pre-existing cell
- Cell is removed by macrophages and neighboring cells that recognizes molecular
flags
- Dysregulated during oncogenesis.
Function of apoptosis:
- Active ATP dependent process
- Physiological in many organs:
o Development morphogenesis → tenen aan elkaar
, o Controls cell numbers
o Removal of damaged cells → cellen die dood gaan na in de zon zitten
o Negative and positive selection of lymphocytes
o Cytotoxic effect of radio and chemotherapy
Mitosis per second: 25 miljoen
Apoptosis per second: 25 miljoen
2,2 kg cells per day
Apoptosis vs. Necrosis
Bij de tweede zijn drugs (chemo) gegeven en zie je dat de cellen apoptosis plegen
Apoptosis signalling:
- Induction of apoptosis:
o Programmed
o Loss of growth factors
o Death receptors of the TNFR family
o T and B cell antigen receptors
o CTLs
, o DNA damage
o Stress conditions
- Mitochondrial changes
- Activation of the caspase family
- Proteolytic cleavage of structural and functional proteins
- Induction of apoptosis morphology
Caspases:
- 3 types:
- Initiator: cleaving effector
- Effector: cleave important proteolytic and key
protein of cell
- Inflammatory: neurodegenerative diseases
- 14 family members cloned
- Caspases are cysteine-proteases synthesized as
zymogens
- Requirement for an aspartatic acid at the P1
position
Four apoptosis pathways
- Intrinsic/stress-induced or mitochondrial apoptosis pathway
- Extrinsic/Death receptor mediated apoptosis pathway
- Granzyme B mediated apoptosis pathway
- ER mediated apoptosis pathway
➢ Two major apoptosis pathways
o Apoptosis induced by internal signals: The intrinsic or mitochondrial pathway
o Apoptosis triggered by external signals: The extrinsic or death receptor
pathway
, When Caspase 3,6,7 are cleaved: they are activated: point of no return. They can also
recognize specific sequence on certain proteins that are involved in important processes:
- nuclear lamins
- Cytoskeletal proteins (actin)
- Intermediate filaments (cell structure)
- Specific kinases for cell signaling
- Other enzymes (caspase-activated DNAse)
Extrinsic apoptosis pathway:
