Een uitgebreide samenvatting van alle colleges van Oncology (AB_1184) uit jaar 2 van Gezondheid en Leven. Het vak wordt in het Engels gegeven (samenvatting is ook Engels). Bevat alle stof voor deeltentamen 2 bestaat uit de hoofdstukken 7 - 14 uit Molecular Biology of Cancer by
Pecorino, 5th editio...
Hoorcollege introduction/planning/explanation group assignment (02-04-2024)
• Exam 1 will contain questions on the practical
• Exam 1 30% of final mark
• Digital online exam with multiple choice questions
• Exam 2 is 60% of the grade
• Workgroup assignment is 10% of the final grade
Workgroup assignment
• Each group assesses an AI generated science journalism article on an oncological topic.
• You will assess and answer questions about this article, rewrite the article; and critically assess
the rewritten article of another student group.
• The assignment contains 6 steps...
1. Receive 2 articles: the AI-generated article, and the original publication it is based on
2. Answer a series of questions about the AI-generated article. Substantiate your answers
3. Rewrite parts of the article, as indicated in the assignment details
Deadline: Friday 26/04 -> Hand in 2 documents on Canvas (assignments)
4. Receive 1 article: the rewritten article from another group
5. Rewrite one part of the article, and explain how you changed it and why
6. Make a table with all the contributions of each team member
Deadline: Friday 31/05 -> Hand in 2 documents on Canvas (assignments)
Important dates/deadlines
• 17/18/19 April 2024: Practical
• 22 April 2024: Exam 1: Chapter 1-6 + Practical
• 26 April 2024: Deadline submission assignment - 1
• 28 May 2024: Exam 2: Chapter 7-14 + Keynote lectures
• 31 May 2024: Deadline submission assignment - 2
• 18 June 2024: Deadline final marks registered in Vunet
• 02 July 2024: Resit exam: entire subject matter
HC1 apoptosis (chapter 7 – week 5)
Definition of apoptosis
• Apoptosis is the regulated and orderly destruction of a cell through a genetically encoded
process also known as programmed cell death (PCD)
• Apoptosis is a type of “cell suicide” that is intrinsic to the cell
• Apoptosis is organized, neat, and tidy, leaving behind little evidence of the preexisting cell
• The cell undergoing apoptosis is swept clean during phagocytosis by macrophages, neighboring
cells that recognize molecular flags (phosphatidyl serine → flipflops outside the cell and iduces
apoptosis)
Function of apoptosis
Active ATP dependent process. Physiological in many organs:
• developmental morphogenesis
• controls cell numbers
• removal of damaged cells. In the intestine after 3-5 days cells will be replaced.
• negative and positive selection of lymphocytes
• cytotoxic effect of radio- and chemotherapy
Estimation of apoptosis in a human:
25 x 106 mitoses per second
25 x 106 apoptosis per second
2,2 kg cells per day
,Apoptosis versus necrosis
Macrophages recognize apoptotic bodies.
Apoptosis morphology in a lymphocyte
A = normal lymphocyte →
small surrounding of
cytoplasm)
C = membrane blebbing
D = condensation
G = apoptotic bodies
Apoptosis signalling
• Induction of apoptosis:
– Programmed
– Loss of growth factors, of adhesion → vaak te zien in the intestine
– Death receptors of the TNFR family
– T- and B cell antigen receptors
– CTLs (cytotoxic T cells)
– DNA damage (irradiation, chemotherapy)
– Stress conditions
• Mitochondrial changes
• Activation of the caspase family
• Proteolytic cleavage of structural and functional proteins
• Induction of apoptosis morphology
, Caspases
• Caspases are cysteine-proteases synthesized as zymogens
• Requirement for an aspartatic acid at the P1 position
• 14 family members cloned
• Caspases 2, 3, 6, 7, 8, 9 and 10 are involved in apoptosis
• Divided into:
o initiators → 2, 8, 9 and 10. Initiator caspases: cleave effector caspases
o effectors → 3, 6 and 7. Cleave key proteins/proteolytic enzymens.
o inflammatory → 1,4 and 5. Manly involved in neurodegenerative diseases (AD or PD)
→ they can cleave because they recognize the specific amino acid sequence.
Caspase activation
Caspase bestaat uit een
1. pro domain
2. large subunit domain
3. spacer
4. small subunit domain
Four Apoptosis pathways
Two major apoptosis pathways:
1. Intrinsic/stress-induced or mitochondrial apoptosis pathway. Apoptosis induced by internal
signals.
2. Extrinsic/Death receptor mediated apoptosis pathway. Apoptosis triggered by external signals.
3. Granzyme B mediated apoptosis pathway
4. ER mediated apoptosis pathway
Intrinsic and Extrinsic apoptosis pathway
Upregulate p53 → stabilization of p53 →
bcl is activated (BH3) → activate BAK and
BAX.
Initiator caspases: 8 & 9
Effector caspases: 3, 6 & 7. When these are
activated there is no point of return
Fas ligand trimerizes in order to cause the
downstream pathway
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