use-linear-accelerator-for-conducting-vitro-radiobiology

Use of a Linear Accelerator for Conducting In Vitro Radiobiology Experiments

Radiation therapy remains one of the cornerstones of cancer management. For most cancers, it is the most effective, nonsurgical therapy to debulk tumors. ...

Cleveland Clinic

In a new report, Bayin et al. described an ex vivo explant model to test the patient-specific response to transforming growth factor-β inhibition in high-grade gliomas.

Precision Medicine with TGF-β Inhibition Using Tumor Explants: Comment on "Patient-Specific Screening Using High-Grade Glioma Explants to Determine Potential Radiosensitization by a TGF-β Small Molecule Inhibitor" by N. Sumru Bayin et al.

Tumor hypoxia is associated with poor patient survival and is a characteristic of glioblastoma. Notch signaling is implicated in maintaining glioma stem-like cells (GSCs) within the hypoxic niche, although the molecular mechanisms linking hypoxia to Notch activation have not been clearly delineated. Here we show that Vasorin is a critical link between hypoxia and Notch signaling in GSCs. Vasorin is preferentially induced in GSCs by a HIF1α/STAT3 co-activator complex and stabilizes Notch1 protein at the cell membrane. This interaction prevents Numb from binding Notch1, rescuing it from Numb-mediated lysosomal degradation. Thus, Vasorin acts as a switch to augment Notch signaling under hypoxic conditions. Vasorin promotes tumor growth and reduces survival in mouse models of glioblastoma, and its expression correlates with increased aggression of human gliomas. These findings provide mechanistic insights into how hypoxia promotes Notch signaling in glioma and identify Vasorin as a potential therapeutic target.

Hypoxic Induction of Vasorin Regulates Notch1 Turnover to Maintain Glioma Stem-like Cells.

Neurodevelopmental programs are frequently dysregulated in cancer. Semaphorins are a large family of guidance cues that direct neuronal network formation and are also implicated in cancer. Semaphorins have two kinds of receptors, neuropilins and plexins. Besides their role in development, semaphorin signaling may promote or suppress tumors depending on their context. Sema3C is a secreted semaphorin that plays an important role in the maintenance of cancer stem-like cells, promotes migration and invasion, and may facilitate angiogenesis. Therapeutic strategies that inhibit Sema3C signaling may improve cancer control. This review will summarize the current research on the Sema3C pathway and its potential as a therapeutic target.

Article	Year
Precision Medicine with TGF-β Inhibition Using Tumor Explants: Comment on "Patient-Specific Screening Using High-Grade Glioma Explants to Determine Potential Radiosensitization by a TGF-β Sm... Neoplasia (New York, N.Y.)\| PubMed ID: 27978995	2016
Hypoxic Induction of Vasorin Regulates Notch1 Turnover to Maintain Glioma Stem-like Cells. Cell stem cell\| PubMed ID: 29198941	2018
Semaphorin 3C and Its Receptors in Cancer and Cancer Stem-Like Cells. Biomedicines\| PubMed ID: 29642487	2018

Jennifer S. Yu

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