Overview:
- Overview of metastasis
- Define each of the general stages of metastasis
- Provide some examples of genes involved in each stage
- Different metastasis models
- Examples of therapeutic options
Temporal course of metastasis:
The latency period of BREAST CARCINOMA is generally
Respuesta
Years to decades
Months
Pregunta 3
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Temporal course of metastasis:
The latency period of COLORECTAL CARCINOMA is generally
Respuesta
Years to decades
Months
Pregunta 4
Pregunta
Temporal course of metastasis:
The latency period of LUNG ADENOCARCINOMA is generally
Respuesta
Months
Years to decades
Pregunta 5
Pregunta
Does stiffening of the ExtraCellular Matrix (ECM) promote or inhibit tumourigenesis?
Respuesta
Promote
Inhibit
Pregunta 6
Pregunta
True or false:
MMPs (Matrix MetalloProteinases) play a role in Intravasation.
Respuesta
True
False
Pregunta 7
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Angiopoietin-like 4 ("ANGPTL4") is involved in:
Respuesta
Extravasation
Intravasation
Both of the above
[none of the above]
Pregunta 8
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The "Cell-of-Origin" model of metastasis progresses as follows:
Respuesta
Normal epithelial cell (already has activated metastasis virulence genes due to its normal cellular differentiation program) > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > Metastatic colonisation
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > Viable partially metastasis-competent disseminated tumour cell > [mutations in metastasis virulence genes]
> Metastatic colonisation
Normal epithelial cell > [series of mutations, including stochastic mutations in metastasis virulence genes] > Primary tumour > [dissemination to a foreign microenvironment] > Metastatic colonisation
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > [additional mutations] > Metastatic colonisation > [re-infiltration of the primary tumour by metastatic cells] > Primary tumour that has undergone self-seeding
Normal epithelial cell > [mutation] > Quasi-normal epithelial cell > [early dissemination to a foreign microenvironment] > Viable disseminated quasi-normal epithelial cell > [series of mutations, including mutations in metastasis virulence genes] > Metastatic colonisation
Pregunta 9
Pregunta
The "Partial-Competence" model of metastasis progresses as follows:
Respuesta
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > Metastatic colonisation
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > Viable partially metastasis-competent disseminated tumour cell > [mutations in metastasis virulence genes]
> Metastatic colonisation
Normal epithelial cell > [series of mutations, including stochastic mutations in metastasis virulence genes] > Primary tumour > [dissemination to a foreign microenvironment] > Metastatic colonisation
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > [additional mutations] > Metastatic colonisation > [re-infiltration of the primary tumour by metastatic cells] > Primary tumour that has undergone self-seeding
Normal epithelial cell > [mutation] > Quasi-normal epithelial cell > [early dissemination to a foreign microenvironment] > Viable disseminated quasi-normal epithelial cell > [series of mutations, including mutations in metastasis virulence genes] > Metastatic colonisation
Pregunta 10
Pregunta
The "Stochastic" model of metastasis progresses as follows:
Respuesta
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > Metastatic colonisation
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > Viable partially metastasis-competent disseminated tumour cell > [mutations in metastasis virulence genes]
> Metastatic colonisation
Normal epithelial cell > [series of mutations, including stochastic mutations in metastasis virulence genes] > Primary tumour > [dissemination to a foreign microenvironment] > Metastatic colonisation
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > [additional mutations] > Metastatic colonisation > [re-infiltration of the primary tumour by metastatic cells] > Primary tumour that has undergone self-seeding
Normal epithelial cell > [mutation] > Quasi-normal epithelial cell > [early dissemination to a foreign microenvironment] > Viable disseminated quasi-normal epithelial cell > [series of mutations, including mutations in metastasis virulence genes] > Metastatic colonisation
Pregunta 11
Pregunta
The "Tumour Self-seeding" model of metastasis progresses as follows:
Respuesta
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > Metastatic colonisation
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > Viable partially metastasis-competent disseminated tumour cell > [mutations in metastasis virulence genes]
> Metastatic colonisation
Normal epithelial cell > [series of mutations, including stochastic mutations in metastasis virulence genes] > Primary tumour > [dissemination to a foreign microenvironment] > Metastatic colonisation
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > [additional mutations] > Metastatic colonisation > [re-infiltration of the primary tumour by metastatic cells] > Primary tumour that has undergone self-seeding
Normal epithelial cell > [mutation] > Quasi-normal epithelial cell > [early dissemination to a foreign microenvironment] > Viable disseminated quasi-normal epithelial cell > [series of mutations, including mutations in metastasis virulence genes] > Metastatic colonisation
Pregunta 12
Pregunta
The "Parallel Progression" model of metastasis progresses as follows:
Respuesta
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > Metastatic colonisation
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > Viable partially metastasis-competent disseminated tumour cell > [mutations in metastasis virulence genes]
> Metastatic colonisation
Normal epithelial cell > [series of mutations, including stochastic mutations in metastasis virulence genes] > Primary tumour > [dissemination to a foreign microenvironment] > Metastatic colonisation
Normal epithelial cell > [series of mutations] > Primary tumour > [dissemination to a foreign microenvironment] > [additional mutations] > Metastatic colonisation > [re-infiltration of the primary tumour by metastatic cells] > Primary tumour that has undergone self-seeding
Normal epithelial cell > [mutation] > Quasi-normal epithelial cell > [early dissemination to a foreign microenvironment] > Viable disseminated quasi-normal epithelial cell > [series of mutations, including mutations in metastasis virulence genes] > Metastatic colonisation