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Winkler Laboratory @winklerlab.bsky.social · 21h

Thank you, @danielazorin.bsky.social and @dirkchoffmann.bsky.social,
on behalf of all of us at the Winkler Lab, for driving this project! It’s exciting new work and the next step towards new therapeutic strategies against this horrific disease.

Winkler Laboratory @winklerlab.bsky.social · 21h

Thank you, @danielazorin.bsky.social and @dirkchoffmann.bsky.social,
on behalf of all of us at the Winkler Lab, for driving this project! It’s exciting new work and the next step towards new therapeutic strategies against this horrific disease.

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Reposted by Winkler Laboratory

Daniel D. Azorín @danielazorin.bsky.social · 21h

My main PhD project is out in #CancerDiscovery @theaacr.bsky.social

We found that PKC activators (TPPB) destroy tumor microtube networks that glioblastoma cells use to invade & resist therapy.

Huge thanks to my first co-author @dirkchoffmann.bsky.social , @winklerlab.bsky.social & all co-authors!

Winkler Laboratory @winklerlab.bsky.social · 1d

How to disconnect therapy-resistant tumor networks in glioblastoma?

In our paper, online @Cancer Discovery, we built an anti-tumor microtube (TM) screening pipeline and found that Protein Kinase C activators disrupt TMs, silence Ca²⁺ “pacemakers” and boost radiotherapy.
doi.org/10.1158/2159...

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Reposted by Winkler Laboratory

Nils Hebach @nilshebach.bsky.social · 21h

Very excited to see this out and happy to have contributed!

Winkler Laboratory @winklerlab.bsky.social · 1d

How to disconnect therapy-resistant tumor networks in glioblastoma?

In our paper, online @Cancer Discovery, we built an anti-tumor microtube (TM) screening pipeline and found that Protein Kinase C activators disrupt TMs, silence Ca²⁺ “pacemakers” and boost radiotherapy.
doi.org/10.1158/2159...

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Reposted by Winkler Laboratory

dirkchoffmann.bsky.social @dirkchoffmann.bsky.social · 1d

#Glioblastoma cells don’t just grow — they extend tumor microtubes that let them invade the brain 🧠 and link into multicellular networks that resist therapy ☢️.
We developed a strategy to inhibit these TMs — and make these cells vulnerable to therapy ☠️.
This study is now online @Cancer Discovery

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Winkler Laboratory @winklerlab.bsky.social · 1d

Thanks to collaborators, funders, and everyone involved. 🤝

Special thanks to patients and their families for donating samples.

Advancing #cancerneuroscience together.

#UNITE-GBM #disconnectGBM
@neurooncologyhd.bsky.social @aacrjournals.bsky.social @dkfz.bsky.social @cn-hd.bsky.social

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Winkler Laboratory @winklerlab.bsky.social · 1d

In summary, we introduce a scalable anti-TM #drugscreening platform and reveal PKC activation as a TM master-regulator.
TM targeting disconnects tumor networks and sensitizes #GBM to #therapy.

#Translational #CancerNeuroscience

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Winkler Laboratory @winklerlab.bsky.social · 1d

Spatial multi-omics analysis (with COMET) of brains revealed that cells in the TPPB/RT combination treatment group exhibited fewer and shorter TMs, reduced proliferation, increased cell death, and decreased TTYH1 expression (a driver of TM invasion)

#GBM #COMET #Lunaphore @bio-techne.bsky.social

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Winkler Laboratory @winklerlab.bsky.social · 1d

Intravital 2-photon microscopy shows how TPPB breaks tumor networks and boosts radiotherapy in mice.

Control+RT → network persists.
TPPB+RT → fewer tumor microtubes, network collapse, regional regression!

#Radiotherapy #IntravitalMicroscopy #preclinicalmodels #invivo

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Winkler Laboratory @winklerlab.bsky.social · 1d

The efficacy of TPPB was substantiated in 3D human glioma cortical spheroids and corroborated by longitudinal intravital imaging of mouse brains and histological analysis.

Precisely, application of TPPB in vivo with radiotherapy reduced tumor burden and conferred a survival benefit vs RT alone.

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Winkler Laboratory @winklerlab.bsky.social · 1d

Likewise, they inhibited global Ca²⁺ activity and pacemaker-like cells fell silent.

#PacemakerCell #calciumimaging #translationalresearch #periodicity

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Winkler Laboratory @winklerlab.bsky.social · 1d

PKC modulators emerged as the lead class of anti-TM drugs. Their members TPPB & PMA reduced TMs per cell and TM length without overt cytotoxicity.

#PKC #tumornetworks

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Winkler Laboratory @winklerlab.bsky.social · 1d

We built a machine-learning based 2D/3D morphometry pipeline to quantify TMs and network activity in 2D GB stem-like cells, 3D human brain spheroids (hGliCS), and mice.

Using this platform, we screened 71 compounds to identify the most potent ones.

#TumorMicrotubes #drugrepurposing

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Winkler Laboratory @winklerlab.bsky.social · 1d

Glioblastoma cells extend TMs to invade and wire into resilient networks.
Particularly these network-integrated cells communicate via Ca²⁺waves and resist standard therapy.
Thus, targeting TMs holds promise to overcome the resistance.

#Glioblastoma #CancerNeuroscience #cancerresearch

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Winkler Laboratory @winklerlab.bsky.social · 1d

How to disconnect therapy-resistant tumor networks in glioblastoma?

In our paper, online @Cancer Discovery, we built an anti-tumor microtube (TM) screening pipeline and found that Protein Kinase C activators disrupt TMs, silence Ca²⁺ “pacemakers” and boost radiotherapy.
doi.org/10.1158/2159...

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Winkler Laboratory @winklerlab.bsky.social · 1d

Thanks to collaborators, funders, and everyone involved. Special thanks to patients for donating their samples. Advancing cancer neuroscience together #GBM #CancerNeuroscience @neurooncologyhd.bsky.social @aacrjournals.bsky.social @dkfz.bsky.social ky.social @cn-hd.bsky.social

ky.social

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Winkler Laboratory @winklerlab.bsky.social · 1d

We introduce a scalable anti-TM drug screening platform and reveal PKC activation as a TM master-regulator. TM targeting disconnects tumor networks and sensitizes GBM to therapy. #Translational #CancerNeuroscience #glioblastoma

1

Winkler Laboratory @winklerlab.bsky.social · 1d

Spatial multi-omics analysis (with COMET) of brains revealed that cells in the TPPB/RT combination treatment group exhibited fewer and shorter TMs, reduced proliferation, increased cell death, and decreased TTYH1 expression (a driver of TM invasion)
#GBM #COMET #Lunaphore @bio-techne.bsky.social

1

Winkler Laboratory @winklerlab.bsky.social · 1d

Intravital 2-photon microscopy with RT: TPPB breaks tumor networks and boosts radiotherapy in mice. Control+RT → network persists. TPPB+RT → fewer tumor microtubes, network collapse, regional regression. #Radiotherapy #IntravitalMicroscopy

1

Winkler Laboratory @winklerlab.bsky.social · 1d

The efficacy of TPPB was substantiated in 3D human glioma cortical spheroids and corroborated by longitudinal intravital imaging of mouse brains and histological analysis. Precisely, application of TPPB in vivo with radiotherapy reduced tumor burden and conferred a survival benefit vs RT alone.

1

Winkler Laboratory @winklerlab.bsky.social · 1d

Likewise, they inhibitied global Ca²⁺ activity and pacemaker-like cells fell silent. #PacemakerCell #calciumimaging #periodicity

1

Winkler Laboratory @winklerlab.bsky.social · 1d

PKC modulators emerged as the lead class of anti-TM drugs. Their members TPPB & PMA reduced TMs per cell and TM length without overt cytotoxicity. #PKC #TMs #cancerneuroscience #cancer

1

Winkler Laboratory @winklerlab.bsky.social · 1d

We built a machine-learning based 2D/3D morphometry pipeline to quantify TMs and network activity in 2D GB stem-like cells, 3D human brain spheroids (hGliCS), and mice. Using this platform, we screened 71 compounds to identify the most potent ones. #TumorMicrotubes

1

Winkler Laboratory @winklerlab.bsky.social · 1d

Glioblastoma cells extend TMs to invade and wire into resilient networks. Particularly these network-integrated cells communicate via Ca²⁺waves and resist standard therapy. Thus, targeting TMs holds promise to overcome the resistance. #Glioblastoma #CancerNeuroscience

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Reposted by Winkler Laboratory

Health + Life Science Alliance Heidelberg Mannheim @hlsalliance.bsky.social · 1d

#CancerNeuroscience Seminar with
Elizabeth Repasky from Roswell Park Comprehensive Cancer Center in Buffalo, NY.
🧠Chronic adrenergic stress and thermoregulation: critical neuro-immune interactions that promote cancer in laboratory mice🐭
🐁Virtual seminar on 10/21 from 5-6 PM, CET, register on zoom.

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