scholarly journals The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma

Oncotarget ◽  
2015 ◽  
Vol 6 (14) ◽  
pp. 12141-12155 ◽  
Author(s):  
Sridevi Yadavilli ◽  
Joseph Scafidi ◽  
Oren J. Becher ◽  
Amanda M. Saratsis ◽  
Rebecca L. Hiner ◽  
...  
Keyword(s):  
Diffuse Intrinsic Pontine Glioma ◽  
Pontine Glioma

scholarly journals The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation

2021 ◽  
Vol 22 (17) ◽  
pp. 9165
Author(s):  
David Roig-Carles ◽  
Holly Jackson ◽  
Katie F. Loveson ◽  
Alan Mackay ◽  
Rebecca L. Mather ◽  
...  
Keyword(s):  
Large Family ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Locked Nucleic Acid ◽  
Normal Brain ◽  
Pontine Glioma ◽  
Incurable Cancer ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG. Herein, we studied the oncogenic role of the development-associated H19 lncRNA in DIPG. Bioinformatic analyses of clinical datasets were used to measure the expression of H19 lncRNA in paediatric high-grade gliomas (pedHGGs). The expression and sub-cellular location of H19 lncRNA were validated in DIPG cell lines. Locked nucleic acid antisense oligonucleotides were designed to test the function of H19 in DIPG cells. We found that H19 expression was higher in DIPG vs. normal brain tissue and other pedHGGs. H19 knockdown resulted in decreased cell proliferation and survival in DIPG cells. Mechanistically, H19 buffers let-7 microRNAs, resulting in the up-regulation of oncogenic let-7 target (e.g., SULF2 and OSMR). H19 is the first functionally characterized lncRNA in DIPG and a promising therapeutic candidate for treating this incurable cancer.

scholarly journals Characterization of the Blood–Brain Barrier Integrity and the Brain Transport of SN-38 in an Orthotopic Xenograft Rat Model of Diffuse Intrinsic Pontine Glioma

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 399 ◽  
Author(s):  
Catarina Chaves ◽  
Xavier Declèves ◽  
Meryam Taghi ◽  
Marie-Claude Menet ◽  
Joelle Lacombe ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Pontine Glioma ◽  
Anticancer Drug Delivery ◽  
Blood Brain ◽  
The Brain

The blood–brain barrier (BBB) hinders the brain delivery of many anticancer drugs. In pediatric patients, diffuse intrinsic pontine glioma (DIPG) represents the main cause of brain cancer mortality lacking effective drug therapy. Using sham and DIPG-bearing rats, we analyzed (1) the brain distribution of 3-kDa-Texas red-dextran (TRD) or [14C]-sucrose as measures of BBB integrity, and (2) the role of major ATP-binding cassette (ABC) transporters at the BBB on the efflux of the irinotecan metabolite [3H]-SN-38. The unaffected [14C]-sucrose or TRD distribution in the cerebrum, cerebellum, and brainstem regions in DIPG-bearing animals suggests an intact BBB. Targeted proteomics retrieved no change in P-glycoprotein (P-gp), BCRP, MRP1, and MRP4 levels in the analyzed regions of DIPG rats. In vitro, DIPG cells express BCRP but not P-gp, MRP1, or MRP4. Dual inhibition of P-gp/Bcrp, or Mrp showed a significant increase on SN-38 BBB transport: Cerebrum (8.3-fold and 3-fold, respectively), cerebellum (4.2-fold and 2.8-fold), and brainstem (2.6-fold and 2.2-fold). Elacridar increased [3H]-SN-38 brain delivery beyond a P-gp/Bcrp inhibitor effect alone, emphasizing the role of another unidentified transporter in BBB efflux of SN-38. These results confirm a well-preserved BBB in DIPG-bearing rats, along with functional ABC-transporter expression. The development of chemotherapeutic strategies to circumvent ABC-mediated BBB efflux are needed to improve anticancer drug delivery against DIPG.

scholarly journals TMIC-25. TUMOR MIGRATION AND ROLE OF MICROENVIRONMENT IN DIFFUSE INTRINSIC PONTINE GLIOMA

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi248-vi248 ◽  
Author(s):  
Madhuri Kambhampati ◽  
Eshini Panditharatna ◽  
Sridevi Yadavilli ◽  
Cheng-Ying Ho ◽  
Lindsay Kilburn ◽  
...  
Keyword(s):  
Diffuse Intrinsic Pontine Glioma ◽  
Pontine Glioma

scholarly journals The Role of Early Post Radiation MRI Scans in Children with Diffuse Intrinsic Pontine Glioma (DIPG)

2010 ◽  
Vol 78 (3) ◽  
pp. S594-S595
Author(s):  
A. Kaushal ◽  
C. Ko ◽  
D. Hammoud ◽  
E. Steffan-Smith ◽  
D. Citrin ◽  
...  
Keyword(s):  
Diffuse Intrinsic Pontine Glioma ◽  
Pontine Glioma ◽  
Mri Scans ◽  
Post Radiation

scholarly journals Role of Early Postradiation Magnetic Resonance Imaging Scans in Children With Diffuse Intrinsic Pontine Glioma

2012 ◽  
Vol 83 (4) ◽  
pp. 1252-1256 ◽  
Author(s):  
Christine Ko ◽  
Aradhana Kaushal ◽  
Dima A. Hammoud ◽  
Emilie A. Steffen-Smith ◽  
Robyn Bent ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Resonance Imaging ◽  
Pontine Glioma

scholarly journals The long non-coding RNA H19 drives the proliferation of diffuse intrinsic pontine glioma with H3K27 mutation

2021 ◽  
Author(s):  
Francesco Crea
Keyword(s):  
Large Family ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Locked Nucleic Acid ◽  
Normal Brain ◽  
Pontine Glioma ◽  
Incurable Cancer ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying molecular drivers of DIPG progression is of utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not been yet elucidated in DIPG. Here, we study the oncogenic role of the development-associated H19 lncRNA in DIPG. Bioinformatic analyses of clinical datasets were used to measure the expression of H19 lncRNA in paediatric high-grade gliomas (pedHGG). Expression and sub-cellular location of H19 lncRNA was validated in DIPG cell lines. Locked nucleic acid antisense oligonucleotides were designed to test the function of H19 in DIPG cells. We found that H19 expression was higher in DIPG vs normal brain tissue and other pedHGGs. H19 knockdown resulted in decreased cell proliferation and survival in DIPG cells. Mechanistically, H19 buffers let-7 microRNAs, resulting in up-regulation of oncogenic let-7 target (e.g SULF2, OSMR). H19 is the first functionally characterized lncRNA in DIPG and a promising therapeutic candidate to treat this incurable cancer.

scholarly journals The H3K36me2 writer-reader dependency in H3K27M-DIPG

2021 ◽  
Vol 7 (29) ◽  
pp. eabg7444
Author(s):  
Jia-Ray Yu ◽  
Gary LeRoy ◽  
Devin Bready ◽  
Joshua D. Frenster ◽  
Ricardo Saldaña-Meyer ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Cellular Proliferation ◽  
Pediatric Brain Tumor ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Pontine Glioma ◽  
Chemically Modified ◽  
Functional Pathway ◽  
Pediatric Brain ◽  
Global Inhibition

Histone H3K27M is a driving mutation in diffuse intrinsic pontine glioma (DIPG), a deadly pediatric brain tumor. H3K27M reshapes the epigenome through a global inhibition of PRC2 catalytic activity and displacement of H3K27me2/3, promoting oncogenesis of DIPG. As a consequence, a histone modification H3K36me2, antagonistic to H3K27me2/3, is aberrantly elevated. Here, we investigate the role of H3K36me2 in H3K27M-DIPG by tackling its upstream catalyzing enzymes (writers) and downstream binding factors (readers). We determine that NSD1 and NSD2 are the key writers for H3K36me2. Loss of NSD1/2 in H3K27M-DIPG impedes cellular proliferation and tumorigenesis by disrupting tumor-promoting transcriptional programs. Further, we demonstrate that LEDGF and HDGF2 are the main readers mediating the protumorigenic effects downstream of NSD1/2-H3K36me2. Treatment with a chemically modified peptide mimicking endogenous H3K36me2 dislodges LEDGF/HDGF2 from chromatin and specifically inhibits the proliferation of H3K27M-DIPG. Our results indicate a functional pathway of NSD1/2-H3K36me2-LEDGF/HDGF2 as an acquired dependency in H3K27M-DIPG.

scholarly journals Role of Radiation Therapy in the Management of Diffuse Intrinsic Pontine Glioma: A Systematic Review

2019 ◽  
Vol 4 (3) ◽  
pp. 520-531 ◽  
Author(s):  
Matthew Gallitto ◽  
Stanislav Lazarev ◽  
Isaac Wasserman ◽  
James M. Stafford ◽  
Suzanne L. Wolden ◽  
...  
Keyword(s):  
Systematic Review ◽  
Radiation Therapy ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Pontine Glioma
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