更新日：2023年3月22日

北条雅人脳神経外科科長と谷垣健二専門研究員が執筆した論文が、PlosOne に掲載されました

• 日付
  2023年3月22日
• 発行日
  2023年3月20日
• 雑誌名
  PlosOne2023 Mar 16；18(3):e0279634. doi: 10.1371/journal.pone.0279634. eCollection 2023.
• 題名
  Inhibition of VEGF receptors induces pituitary apoplexy: An experimental study in mice
• 執筆者
  SugitaY, Takada S, Tanigaki K, Muraki K, Uemura M , Hojo M, Miyamoto S
• 要旨
  Anti-vascular endothelial growth factor (VEGF) therapy has been developed for the treatment of a variety of cancers.
  Although this therapy may be a promising alternative treatment for refractory pituitary adenomas and pituitary carcinomas, the effects of anti-VEGF agents on the pituitary gland are not yet well understood.
  Here, we found that mice administered with OSI-930, an inhibitor of receptor tyrosine kinases including VEGF receptor 1 and 2, frequently exhibited hemorrhage in the pituitary gland. This is the first report that anti-VEGF therapy can cause pituitary apoplexy.
  Pituitary glands were immunohistochemically examined. Four of six mice treated for three days and all of five mice treated for six days exhibited hemorrhage in the pituitary gland.
  C57BL/6 mice were daily injected intraperitoneally with 100 mg/kg body weight of OSI-930 for one to six days. In all cases, the hemorrhage occurred just around Rathke’s cleft.
  In OSI-930-administered mice, the vascular coverage and branching were reduced in the anterior lobe, and capillary networks were also decreased in the intermediate lobe in a treatment-day dependent manner.
  Few blood vessels around Rathke’s cleft of the intermediate lobe express VE-cadherin and are covered with platelet-derived growth factor receptor-β (PDGFR-β)-positive cells, which suggests that capillaries around Rathke’s cleft of the intermediate lobe were VE-cadherin-negative and not covered with pericytes.
  The reduction of capillary plexus around Rathke’s cleft was observed at the site wherehemorrhage occurred, suggesting a causal relationship with the pathogenesis of pituitary hemorrhage.
  Our study demonstrates that anti-VEGF agents have a risk of pituitary apoplexy. Pituitary apoplexy should be kept in mind as an adverse effect of anti-VEGF therapy.
• 要旨(日本語要約)
  悪性神経膠腫を始め多くの悪性腫瘍の治療にVEGF阻害薬が使用されている。この研究では、動物モデルを用い、高濃度のVEGF阻害剤OSI930投与が高率に下垂体出血を起こすことを見出した。この研究結果はVEGF阻害剤の副作用として下垂体卒中が起こる可能性があるか検討する意義があることを示唆しています。