PMID- 27982767
OWN - NLM
STAT- MEDLINE
DCOM- 20190815
LR  - 20190815
IS  - 1933-0693 (Electronic)
IS  - 0022-3085 (Linking)
VI  - 127
IP  - 3
DP  - 2017 Sep
TI  - Octreotide therapy in meningiomas: in vitro study, clinical correlation, and 
      literature review.
PG  - 660-669
LID - 10.3171/2016.8.JNS16995 [doi]
AB  - OBJECTIVE Meningiomas express somatostatin receptor subtype 2 (SST2), which is 
      targeted by the somatostatin analog octreotide. However, to date, using 
      somatostatin analog therapy for the treatment of these tumors in clinical 
      practice has been debated. This study aims to clarify the in vitro effects of 
      octreotide on meningiomas for precise clinical applications. METHODS The effects 
      of octreotide were analyzed in a large series of 80 meningiomas, including 31 
      World Health Organization (WHO) Grade II and 4 WHO Grade III tumors, using fresh 
      primary cell cultures to study the impact on cell viability, apoptosis, and 
      signal transduction pathways. RESULTS SST2 mRNA was detected in 100% of the 
      tested meningiomas at levels similar to those observed in other SST2-expressing 
      tumors, neuroendocrine tumors, or pituitary adenomas. Octreotide significantly 
      decreased cell proliferation in 88% of meningiomas but did not induce cell death. 
      On average, cell proliferation was more inhibited in the meningioma group 
      expressing a high level of SST2 than in the low-SST2 group. Moreover, octreotide 
      response was positively correlated to the level of merlin protein and inversely 
      correlated to the level of phosphorylated p70-S6 kinase, a downstream effector of 
      the PI3K/Akt/mammalian target of rapamycin (mTOR) pathway. Octreotide inhibited 
      Akt phosphorylation and activated tyrosine phosphatase without impacting the 
      extracellular regulated kinase (ERK) pathway. CONCLUSIONS Octreotide acts 
      exclusively as an antiproliferative agent and does not promote apoptosis in 
      meningioma in vitro. Therefore, in vivo, octreotide is likely to limit tumor 
      growth rather than induce tumor shrinkage. A meta-analysis of the literature 
      reveals an interest in octreotide for the treatment of WHO Grade I tumors, 
      particularly those in the skull base for which the 6-month progression-free 
      survival level reached 92%. Moreover, somatostatin analogs, which are 
      well-tolerated drugs, could be of interest for use as co-targeting therapies for 
      aggressive meningiomas.
FAU - Graillon, Thomas
AU  - Graillon T
AD  - Aix-Marseille Universite, CNRS, CRN2M, UMR 7286.
AD  - Departments of 2 Neurosurgery.
FAU - Romano, David
AU  - Romano D
AD  - Aix-Marseille Universite, CNRS, CRN2M, UMR 7286.
FAU - Defilles, Celine
AU  - Defilles C
AD  - Aix-Marseille Universite, CNRS, CRN2M, UMR 7286.
FAU - Saveanu, Alexandru
AU  - Saveanu A
AD  - Aix-Marseille Universite, CNRS, CRN2M, UMR 7286.
FAU - Mohamed, Amira
AU  - Mohamed A
AD  - Aix-Marseille Universite, CNRS, CRN2M, UMR 7286.
FAU - Figarella-Branger, Dominique
AU  - Figarella-Branger D
AD  - Pathology and Brain Pathology, and.
FAU - Roche, Pierre-Hugues
AU  - Roche PH
AD  - Department of Neurosurgery, Hopital Nord, AP-HM, Marseille, France.
FAU - Fuentes, Stephane
AU  - Fuentes S
AD  - Departments of 2 Neurosurgery.
FAU - Chinot, Olivier
AU  - Chinot O
AD  - Neuro-oncology, Hopital La Timone, AP-HM; and.
FAU - Dufour, Henry
AU  - Dufour H
AD  - Departments of 2 Neurosurgery.
FAU - Barlier, Anne
AU  - Barlier A
AD  - Aix-Marseille Universite, CNRS, CRN2M, UMR 7286.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
DEP - 20161216
PL  - United States
TA  - J Neurosurg
JT  - Journal of neurosurgery
JID - 0253357
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - RWM8CCW8GP (Octreotide)
MH  - Antineoplastic Agents, Hormonal/pharmacology/*therapeutic use
MH  - Cell Proliferation/drug effects
MH  - Correlation of Data
MH  - Humans
MH  - In Vitro Techniques
MH  - Meningioma/*drug therapy
MH  - Octreotide/pharmacology/*therapeutic use
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - BrdU = bromodeoxyuridine
OT  - ERK = extracellular regulated kinase
OT  - GEP-NET = gastroenteropancreatic neuroendocrine tumor
OT  - PBS = phosphate-buffered saline
OT  - PCR = polymerase chain reaction
OT  - PFS6 = 6-month progression-free survival
OT  - SST = somatostatin receptor
OT  - SST2
OT  - SST2 = SST subtype 2
OT  - VEGF = vascular endothelial growth factor
OT  - WHO = World Health Organization
OT  - mTOR = mammalian target of rapamycin
OT  - meningioma
OT  - merlin
OT  - octreotide
OT  - somatostatin
OT  - therapy
OT  - betaGus = beta-glucuronidase
EDAT- 2016/12/17 06:00
MHDA- 2019/08/16 06:00
CRDT- 2016/12/17 06:00
PHST- 2016/12/17 06:00 [pubmed]
PHST- 2019/08/16 06:00 [medline]
PHST- 2016/12/17 06:00 [entrez]
AID - 10.3171/2016.8.JNS16995 [doi]
PST - ppublish
SO  - J Neurosurg. 2017 Sep;127(3):660-669. doi: 10.3171/2016.8.JNS16995. Epub 2016 Dec 
      16.