Renske de Veer (rdeveer)
MIN04 SUMMARY
1. Imaging techniques
UV light: can cause mutations/damage to samples.
Infrared light: warms up samples (enzyme → denatured)
Multiplexing: looking at more proteins at the same time.
Optical microscopy (mouse brain) vs electron microscopy (small molecule)
Principle of light microscopy vs transmission electron microscopy
Electron microscopy examples
,Renske de Veer (rdeveer)
Cancer cells mimic podosomes to invade
- Podosome: conical, actin-rich structures found on the outer surface of the plasma membrane
of animal cells. They display a pattern of distribution in migrating cells, situating at the frond
border between the lamellipodium and lamellum. Primary purpose is connected to cellular
motility and invasion: attachment and degradation along extracellular matrix.
- Invadopodia are sites of intense matrix degradation.
Metastatic cascade
- Tracking of 1/multiple (cancer) cells via 3D in vitro cultures (spheroids) or intravital
microscopy of tissues in living animal.
Quantification of tissue characteristics
- Vessel density or proliferation activity in tumour tissue: relevant for prognosis
o Vessel quantification: identification of immunostained objects. (vessel segmentation:
automatic recognition and outlining of stained structures).
- Amyloid burden in alzheimer brain tissue: analysis of treatment effects in animal models.
From human imaging to small animal imaging: positron emission tomography (PET) or single photon
emission computed tomography (SPECT). Useful in monitoring therapeutic effect of new anti-cancer
drug.
2. Cancer treatments
,Renske de Veer (rdeveer)
Transforming therapeutic landscape
Local treatment: surgery, radiation therapy
Systemically therapy: targeted therapy, immune therapy,
chemotherapy.
Targeted therapy: target specific signal (mutation)
- ERK pathway: BRAFi → cancers develop resistance to
Vemurafenib & Dabrafenib. Develop MEK inhibitor
(Trametinib and Cobimetinib).
o Vemurafenib
o Dabrafenib
Cancer immunity
, Renske de Veer (rdeveer)
Immunotherapy
- Non-antigen specific: stimulate immune system
o Non antigen specific stimulation of
cytokines/growth factors/chemokines
▪ BCG (Bacille Calmette-Guerin)
• Intralesional injection
• No effect in metastatic
melanoma
▪ IFNa
• PFS improved
• OS not improved
• Severe side effects
▪ IL-2
• Some patients respond
• Severe side effects
o Immune checkpoint inhibitors
▪ Anti-CTLA4
• APC & T-Cells
▪ Anti-PD1
• T-cell & tumour
o T-VEC (Talimogene Laherparepvec)
▪ Oncolytic immune therapy
▪ Genetically modified herpes simples type 1 virus (HSV-1)
▪ Antigen non-specific/specific
▪ Mechanism: Modified HSV-1 virus invades and replicates in tumour cell
selectively. Tumour cells produce GM-CSF and will be lysed.
MIN04 SUMMARY
1. Imaging techniques
UV light: can cause mutations/damage to samples.
Infrared light: warms up samples (enzyme → denatured)
Multiplexing: looking at more proteins at the same time.
Optical microscopy (mouse brain) vs electron microscopy (small molecule)
Principle of light microscopy vs transmission electron microscopy
Electron microscopy examples
,Renske de Veer (rdeveer)
Cancer cells mimic podosomes to invade
- Podosome: conical, actin-rich structures found on the outer surface of the plasma membrane
of animal cells. They display a pattern of distribution in migrating cells, situating at the frond
border between the lamellipodium and lamellum. Primary purpose is connected to cellular
motility and invasion: attachment and degradation along extracellular matrix.
- Invadopodia are sites of intense matrix degradation.
Metastatic cascade
- Tracking of 1/multiple (cancer) cells via 3D in vitro cultures (spheroids) or intravital
microscopy of tissues in living animal.
Quantification of tissue characteristics
- Vessel density or proliferation activity in tumour tissue: relevant for prognosis
o Vessel quantification: identification of immunostained objects. (vessel segmentation:
automatic recognition and outlining of stained structures).
- Amyloid burden in alzheimer brain tissue: analysis of treatment effects in animal models.
From human imaging to small animal imaging: positron emission tomography (PET) or single photon
emission computed tomography (SPECT). Useful in monitoring therapeutic effect of new anti-cancer
drug.
2. Cancer treatments
,Renske de Veer (rdeveer)
Transforming therapeutic landscape
Local treatment: surgery, radiation therapy
Systemically therapy: targeted therapy, immune therapy,
chemotherapy.
Targeted therapy: target specific signal (mutation)
- ERK pathway: BRAFi → cancers develop resistance to
Vemurafenib & Dabrafenib. Develop MEK inhibitor
(Trametinib and Cobimetinib).
o Vemurafenib
o Dabrafenib
Cancer immunity
, Renske de Veer (rdeveer)
Immunotherapy
- Non-antigen specific: stimulate immune system
o Non antigen specific stimulation of
cytokines/growth factors/chemokines
▪ BCG (Bacille Calmette-Guerin)
• Intralesional injection
• No effect in metastatic
melanoma
▪ IFNa
• PFS improved
• OS not improved
• Severe side effects
▪ IL-2
• Some patients respond
• Severe side effects
o Immune checkpoint inhibitors
▪ Anti-CTLA4
• APC & T-Cells
▪ Anti-PD1
• T-cell & tumour
o T-VEC (Talimogene Laherparepvec)
▪ Oncolytic immune therapy
▪ Genetically modified herpes simples type 1 virus (HSV-1)
▪ Antigen non-specific/specific
▪ Mechanism: Modified HSV-1 virus invades and replicates in tumour cell
selectively. Tumour cells produce GM-CSF and will be lysed.
