100% tevredenheidsgarantie Direct beschikbaar na betaling Zowel online als in PDF Je zit nergens aan vast
logo-home
Samenvatting Oncobiology (G0W23A) €9,99   In winkelwagen

Samenvatting

Samenvatting Oncobiology (G0W23A)

1 beoordeling
 25 keer bekeken  2 keer verkocht

Biochemie en de Biotechnologie De powerpoint, samen met goede en zeer volledige lesnotities (!) worden samengevat tot een soort van cursus/samenvatting. Het volgt dus de structuur van de powerpoints! Behaald: 1ste zittijd , 20/20 Prof: Jan Cools

Voorbeeld 4 van de 67  pagina's

  • 3 oktober 2023
  • 67
  • 2022/2023
  • Samenvatting
Alle documenten voor dit vak (4)

1  beoordeling

review-writer-avatar

Door: nezqba • 5 maanden geleden

avatar-seller
feline2
ONCOBIOLOGY

Chapter 1 : Introduction hallmarks

1. The development of cancer

• The development of cancer
• Development of cancer
o = slow process
o 1) Start from Normal cells
▪ → cells accumulate mutations pure randomly due to cell division (making mistakes while
copying DNA & sometimes the repair mechanism does not work)
▪ → mutations can be enhanced by a cancer-causing agent: inherited genetic defect, chemical
carcinogens, viral infection, UV light etc
▪ → leads to genetic changes: activation of oncogenes, inactivation of tumor suppressor genes
▪ Opm: in 99% of the tumors, multiple genetic changes are needed for cancer cell
development from a normal cell
o 2) Transformed cells
▪ → metastasis etc.
o Opm: mostly multiple genetic changes are needed for cancer cell development from a normal cell (*)
▪ First mutation in 1 cell giving better proliferation & survival → division into 2 cells with same
first mutation → … → finally 1000 cells with same first mutation → some cells will
accumulate a second mutation (different in other cells: heterogeneity) → which gives more
advantage → …… → cancer development
• Tumor development in the gut
o Duration: 20-40yrs
o Consecutive steps:
▪ 1) Normal epithelium of the gut
▪ 2) losing APC (= tumorsupressor gene) → more proliferation
• = Early adenoma/dysplastic crypt
▪ 3) KRAS mutation → more proliferation
• = Late adenoma
▪ 4) losing TP53 → more proliferation
• = Carcinoma
▪ 5) Other changes → metastasis to spread through the body
• Acute leukemia cells contain 10 to 20 mutations (multiple mutations): targeting




o Notch mutations induce proliferation of cells
o Kinase and signaling protein mutations induce proliferation of cells (rood)
o Changes in epigenetic factors change gene expression
o Ribosomal defects change protein translation
1

, o Transcription factor mutations leading to overexpression etc.
• Proposed model for the development of leukemia
o = the transformation of a bloodcell into a leukemia cell by multiple mutations
o 1) Hematopoietic stem cells
o 2) Committed progenitor cells: myeloid and lymphoid
▪ 1 cell acquire a first mutation and becomes a pre-leukemic cell & multiplies (when the
mutation causes an advantage)
o 3) Differentiated hematopoietic cells & leukemia cells
▪ 1 cell acquire multiple mutations and become a leukemia cell & multiplies (when the
mutation causes an advantage)
▪ Leukemia cells contain:
• 1) major clones = have mutations that are the most effective to transform cells to
leukemia cells (most leukemia cells have these mutations)
• 2) minor clones = have slightly different mutations than major clone (1% of the
leukemia cells have these mutations)
▪ → This leads to Heterogenity of leukemia (similar for solid tumor)
• = same patient has different cells with different mutations
• Diagnosis & treatment of leukemia (similar for solid tumor)
o Diagnosis of leukemia happens through visualizing the major clones (leukemic stage), as the minor
close are more difficult to see
o However for treatment of leukemia it is important to treat both minor & major clones
▪ Reden: when only treating (chemo, drugs) major clones, the major clones are killed → but
the minor clones are less sensitive to the treatment & cause relapse
▪ Solution: use single cell analysis to also identify minor clones & study them
• Same principles apply for solid tumors ipv leukemia
• Accumulation and selection of mutations drive cancer development (solid tumor) (*)
o A solid tumor can have other mutations at the bottom vs the top
▪ → take into account during diagnosis & biopsy
• The evolution of new species = similar to evolution of the tumor: selection (of the fittest) is the key
• 6 hallmarks of cancer (proposed in 2000)
o 1) Sustaining proliferative signaling
o 2) Evading growth suppressors
o 3) Activating invasion and metastasis
o 4) Enabling replicative immortality
o 5) Inducing angiogenesis: new bloodvessel formation for delivering O2 to & removing toxic products
from growing tumor
o 6) Resisting cell death/apoptosis
o → all (most) hallmarks are present during diagnosis of a tumor
▪ Vb: small tumors & leukemia (floating in blood) do not need angiogenesis
o → hallmarks are linked to certain mutations:
▪ Mutation in p53 (inactive) → proliferation
▪ Mutation in Bcl2 (overexpression) → resisting apoptosis
o → order of acquiring the hallmarks can be different from tumor to tumor
• Establishing hallmarks by affecting signaling pathways in cancer cells by mutations
o Vb mutations in growth factors, activating receptors → signaling → proliferation & survival
o Vb: mutations in tyrosine kinase receptors, RAS, PTEN (neg regulator of PI3K), JAK/STAT
o Vb: mutations in Bcl2, bax, fas (all involved in apoptosis)
o Downstream of mutations in cancer cells, you get changes in gene expression (through TF etc)
▪ → used for diagnosis: cells with similar changes in gene expression have similar mutations
• Two additional hallmarks of cancer (proposed in 2011) & two characteristics of cancer

2

, o Emerging hallmarks
▪ 1) Deregulating cellular energetics (metabolism) (both cause & consequence of cancer)
▪ 2) Avoiding immune destruction
o Enabling characteristics
▪ 1) Genome instability and mutation
• → cancer cells have no stable genome, thus keep on accumulating mutations
▪ 2) Tumor-promoting inflammation
• Ten hallmarks of cancer: implications for therapy




• Cancer is a heterogenous tissue
o 1) Cancer cells (CC) with different mutations
o 2) Cancer stem cell (CSC)
o 3) Cancer-Associated fibroblast (CAF)
o 4) Normal cells (stromal cells/stroma)
▪ 1) Endothelial cells (EC)
▪ 2) Pericyte (PC)
▪ 3) Immune, inflammatory cells (ICs) (B & T cells)
o Examples
▪ Hodgkin lymphoma: contains 1% tumor cells (with mutations), 99% normal cells reacting to
the tumor
▪ Leukemia, solid tumors: contains > 99% tumor cells, few normal cells




3

, • Interactions between the cancer cells and the normal cells (an between each other)




o 1) CC produce Hedgehog factor (Hh) & PDGF → stimulating proliferation & production of HGF by
Cancer-associated fibroblast → HGF induces own CC proliferation
o 2) CC produce VEGF → stimulating endothelial cells (for BV formation)
o 3) Tumor-promoting-inflammatory cells produce EGF → stimulating CC
o 4) Tumor-promoting-inflammatory cells produce VEGF → stimulating endothelial cells
o → normal cells can help CC to grow by interaction
o → normal cells can help CC to not be recognized by the IS
o → some growth factors (interaction) are thus target for therapy (using antibodies)
• Interactions between the cancer cells and the normal cells are needed at all stages of cancer development




o 1) Incipient CC & CSC = have few mutations → start already to interact with normal cells
o 2) When CC grow more & more → still interact with normal cells
o 2) When CC move via blood to diff tissue (metastasis) → still interact with normal cells in new tissue




4

Voordelen van het kopen van samenvattingen bij Stuvia op een rij:

√  	Verzekerd van kwaliteit door reviews

√ Verzekerd van kwaliteit door reviews

Stuvia-klanten hebben meer dan 700.000 samenvattingen beoordeeld. Zo weet je zeker dat je de beste documenten koopt!

Snel en makkelijk kopen

Snel en makkelijk kopen

Je betaalt supersnel en eenmalig met iDeal, Bancontact of creditcard voor de samenvatting. Zonder lidmaatschap.

Focus op de essentie

Focus op de essentie

Samenvattingen worden geschreven voor en door anderen. Daarom zijn de samenvattingen altijd betrouwbaar en actueel. Zo kom je snel tot de kern!

Veelgestelde vragen

Wat krijg ik als ik dit document koop?

Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.

Tevredenheidsgarantie: hoe werkt dat?

Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.

Van wie koop ik deze samenvatting?

Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper feline2. Stuvia faciliteert de betaling aan de verkoper.

Zit ik meteen vast aan een abonnement?

Nee, je koopt alleen deze samenvatting voor €9,99. Je zit daarna nergens aan vast.

Is Stuvia te vertrouwen?

4,6 sterren op Google & Trustpilot (+1000 reviews)

Afgelopen 30 dagen zijn er 84251 samenvattingen verkocht

Opgericht in 2010, al 14 jaar dé plek om samenvattingen te kopen

Start met verkopen
€9,99  2x  verkocht
  • (1)
  Kopen