PMID- 37284626
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230608
IS  - 2699-4445 (Electronic)
IS  - 2699-4445 (Linking)
VI  - 2
DP  - 2021 Jan
TI  - The neurovascular unit in diffuse intrinsic pontine gliomas.
LID - 2-17 [pii]
LID - 10.17879/freeneuropathology-2021-3341 [doi]
AB  - Aims: Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with 
      a median overall survival of eleven months. Lack of chemotherapy efficacy may be 
      related to an intact blood-brain barrier (BBB). In this study we aim to 
      investigate the neurovascular unit (NVU) in DIPG patients. Methods: DIPG biopsy 
      (n = 4) and autopsy samples (n = 6) and age-matched healthy pons samples (n = 20) 
      were immunohistochemically investigated for plasma protein extravasation, and the 
      expression of tight junction proteins claudin-5 and zonula occludens-1 (ZO-1), 
      basement membrane component laminin, pericyte marker PDGFR-beta, and efflux 
      transporters P-gp and BCRP. The mean vascular density and diameter were also 
      assessed. Results: DIPGs show a heterogeneity in cell morphology and evidence of 
      BBB leakage. Both in tumor biopsy and autopsy samples, expression of claudin-5, 
      ZO-1, laminin, PDGFR-beta and P-gp was reduced compared to healthy pontine tissues. 
      In DIPG autopsy samples, vascular density was lower compared to healthy pons. The 
      density of small vessels (<10 microm) was significantly lower (P<0.001), whereas the 
      density of large vessels (>/=10 microm) did not differ between groups (P = 0.404). The 
      median vascular diameter was not significantly different: 6.21 microm in DIPG autopsy 
      samples (range 2.25-94.85 microm), and 6.26 microm in controls (range 1.17-264.77 microm). 
      Conclusion: Our study demonstrates evidence of structural changes in the NVU in 
      DIPG patients, both in biopsy and autopsy samples, as well as a reduced vascular 
      density in end-stage disease. Adding such a biological perspective may help to 
      better direct future treatment choices for DIPG patients.
FAU - El-Khouly, Fatma E
AU  - El-Khouly FE
AD  - Emma Children's Hospital, Amsterdam UMC - location VUmc, Department of Pediatric 
      Oncology, Cancer Center Amsterdam Netherlands.
AD  - Princess Maxima Center for Pediatric Oncology, Utrecht Netherlands.
FAU - Haumann, Rianne
AU  - Haumann R
AD  - Emma Children's Hospital, Amsterdam UMC - location VUmc, Department of Pediatric 
      Oncology, Cancer Center Amsterdam Netherlands.
AD  - Princess Maxima Center for Pediatric Oncology, Utrecht Netherlands.
FAU - Breur, Marjolein
AU  - Breur M
AD  - Amsterdam UMC - location VUmc, Department of Pathology, de Boelelaan 1117, 
      Amsterdam Netherlands.
FAU - Veldhuijzen van Zanten, Sophie E M
AU  - Veldhuijzen van Zanten SEM
AD  - Emma Children's Hospital, Amsterdam UMC - location VUmc, Department of Pediatric 
      Oncology, Cancer Center Amsterdam Netherlands.
AD  - Princess Maxima Center for Pediatric Oncology, Utrecht Netherlands.
FAU - Kaspers, Gertjan J L
AU  - Kaspers GJL
AD  - Emma Children's Hospital, Amsterdam UMC - location VUmc, Department of Pediatric 
      Oncology, Cancer Center Amsterdam Netherlands.
AD  - Princess Maxima Center for Pediatric Oncology, Utrecht Netherlands.
FAU - Hendrikse, N Harry
AU  - Hendrikse NH
AD  - Amsterdam UMC - location VUmc, Department of Clinical Pharmacology & Pharmacy, 
      Amsterdam Netherlands.
AD  - Amsterdam UMC - location VUmc, Department of Radiology & Nuclear Medicine, 
      Amsterdam Netherlands.
FAU - Hulleman, Esther
AU  - Hulleman E
AD  - Emma Children's Hospital, Amsterdam UMC - location VUmc, Department of Pediatric 
      Oncology, Cancer Center Amsterdam Netherlands.
AD  - Princess Maxima Center for Pediatric Oncology, Utrecht Netherlands.
FAU - van Vuurden, Dannis G
AU  - van Vuurden DG
AD  - Emma Children's Hospital, Amsterdam UMC - location VUmc, Department of Pediatric 
      Oncology, Cancer Center Amsterdam Netherlands.
AD  - Princess Maxima Center for Pediatric Oncology, Utrecht Netherlands.
FAU - Bugiani, Marianna
AU  - Bugiani M
AD  - Amsterdam UMC - location VUmc, Department of Pathology, de Boelelaan 1117, 
      Amsterdam Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20210705
PL  - Germany
TA  - Free Neuropathol
JT  - Free neuropathology
JID - 101768755
PMC - PMC10227752
OTO - NOTNLM
OT  - Blood-brain barrier (BBB)
OT  - Brainstem
OT  - Diffuse intrinsic pontine glioma (DIPG)
OT  - Neurovascular unit (NVU)
OT  - Pons
OT  - Tight junctions
EDAT- 2021/07/05 00:00
MHDA- 2021/07/05 00:01
PMCR- 2021/07/05
CRDT- 2023/06/07 09:52
PHST- 2021/04/24 00:00 [received]
PHST- 2021/06/27 00:00 [accepted]
PHST- 2021/07/05 00:01 [medline]
PHST- 2021/07/05 00:00 [pubmed]
PHST- 2023/06/07 09:52 [entrez]
PHST- 2021/07/05 00:00 [pmc-release]
AID - 2-17 [pii]
AID - 10.17879/freeneuropathology-2021-3341 [doi]
PST - epublish
SO  - Free Neuropathol. 2021 Jul 5;2:2-17. doi: 10.17879/freeneuropathology-2021-3341. 
      eCollection 2021 Jan.