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Phase 2 - P&I > Week 2 > Flashcards

Week 2 Flashcards

1
Q

What is metastasis?

A

Spread of tumour to- and growth at- ectopic sites, via blood, lymphatics, intra-epithelial route, or trans-coelomic

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2
Q

What is invasion?

A

Growth by infiltration and destruction of surrounding tissues

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3
Q

What is the tissue of origin of carcinoma?

A

Malignant tumour derived from epithelial cells

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4
Q

What is the tissue of origin of sarcoma?

A

Malignant tumours derived from mesenchymal cells

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5
Q

What is the tissue of origin of melanoma?

A

Malignant tumour derived from neural crest cells

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6
Q

What is the tissue of origin of leukaemia?

A

Malignant tumour derived from circulating WBCs

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7
Q

What is the tissue of origin of lymphoma?

A

Malignant tumour derived from lymphatic system

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8
Q

Describe the basement membrane (BM):

A
  • delineates epithelial or endothelial tissues
  • secreted by basal epithelial cells/endothelial cells
  • a layer of extracellular matrix (ECM)
  • fibronectin, type IV collagen, laminin, etc
  • a barrier to spread (esp. carcinoma cells)
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9
Q

What events makes up the metastatic cascade?

A

local invasion -> neovascularisation/angiogenesis -> detachment -> intravasation (into blood or lymph) -> transport -> lodgement/arrest -> extravasation -> growth at ectopic site -> local invasion

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10
Q

What are the main properties of metastatic tumour cells?

A
  1. reduced cell-cell adhesion
  2. altered cell-substratum adhesion
  3. increased motility
  4. increased proteolytic ability
  5. angiogenic ability
  6. ability to intravasate and extravasate
  7. ability to proliferate (locally and in ectopic sites)

1-4 common to invasion and metastasis, 5-7 specific to metastasis

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11
Q

What must be disrupted for cell-cell adhesion to be broken?

A

E-cadherin (e-CD) in adherens junctions

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12
Q

How does cell-cell adhesion occur?

A

Homotypic adhesion (ligand and receptor are same)- e-CD binds e-CD on adjacent cells (like a zip or a tent-peg)

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13
Q

What does e-CD attach to inside the cell?

A

alpha and beta catenin, and the actin-myosin cytoskeleton

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14
Q

What does e-CD require for adhesion?

A

Calcium (2+) in the extracellular space

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15
Q

What indirect mechanisms can disturb e-CD adhesion between cells?

A

Exon-skipping, methylation of e-CD promoter, mutations in proteins that interact with e-CD (beta-catenin, APC) and mutations in transcription factors that regulate e-CD (snail, slug, twist)

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16
Q

What are integrins?

A
  • Cell adhesion molecules (CAMs), integral to plasma membrane, bind to ECM molecules
  • Found in basal epithelial cells and in focal adhesions of migrating cells
17
Q

What are the possible mechanisms of integrins in metastasis?

A
  • decreased adhesion to BM surrounding epithelium
  • increased migration through stroma
  • increased adhesion to BM or endothelial cells of BVs
  • binding site for proteolytic enzymes
18
Q

What is HGF?

A
  • Hepatic growth factor or ‘scatter factor’ can induce epithelial cells to dissociate and scatter in culture
  • HGF is a mitogen (GF), a motogen (motility factor) and a morphogen
19
Q

What cells are associated with the tumour microenvironment (TME)?

A
  • Cancer-associated fibroblasts (CAFs)
  • Immune cells that have infiltrated the tumour
  • myofibroblasts
  • tumour-associated vasculature
  • pericytes
    Secreting;
  • GFs
  • chemokines
  • enzymes
20
Q

What are the site-specific metastasis for breast tumours?

A

Bone, lungs, liver and brain

21
Q

What are the site-specific metastasis for lung adenocarcinoma?

A

Brian, bones, adrenal gland, liver

22
Q

What are the site-specific metastasis for skin melanoma?

A

Lungs, brain, skin, liver

23
Q

What are the site-specific metastasis for colorectal tumours?

A

Liver and lungs

24
Q

What are the site-specific metastasis for pancreatic tumours?

A

Liver and lungs

25
Q

What are the site-specific metastasis for prostate tumours?

A

Bones

26
Q

What are the site-specific metastasis for sarcoma tumours?

A

Lungs

27
Q

What are the site-specific metastasis for uveal melanoma tumours?

A

Liver

28
Q

What are some of the possible mechanisms for organ tropism?

A
  • Selective adhesion to endothelium of target organs
  • Selective response to GFs at ectopic site
  • Selective migration to CK source
  • Factors released by tumour/other cells cause changes in prospective TME at secondary sites, creating pre-metastatic niche
  • Balance of local angiogenic factors versus systemic anti-angiogenic factors (angiostatin and endostatin)

Phase 2 - P&I (4 decks)

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