ABSTRACT
N6-methylation of adenosine (m6A) is one of the most frequent chemical modifications in eukaryotic RNAs and plays a vital role in tumorigenesis and progression. Recently, emerging studies have shown that m6A modification by ALKBH5 was associated with immunotherapy response in various types of cancer. However, whether m6A demethylases ALKBH5 participate in regulating the tumor immune microenvironment and the efficacy of immunotherapy in glioblastoma remain unknown. Here, we found that deletion of ALKBH5 significantly inhibited the growth of glioma allografts, rescued the antitumoral immune response, and increased cytotoxic lymphocyte infiltration and proinflammatory cytokines in CSF while significantly suppressing PD-L1 protein expression. m6A-methylated RNA immunoprecipitation sequencing and RNA sequencing identify ZDDHC3 as the direct target of ALKBH5. Mechanically, ALKBH5 deficiency impairs the YTHDF2-mediated stability of ZDHHC3 mRNA, thereby suppressing PD-L1 expression by accelerating PD-L1 degradation in glioma. In addition, genetic deletion or pharmacological inhibition of ALKBH5 with IOX1 enhances the therapeutic efficacy of anti-PD-1 treatment in preclinical mice models. These data suggest that the combination of anti-PD-1 therapy and ALKBH5 inhibition may be a promising treatment strategy in glioma.
ABSTRACT
OBJECTIVE: To explore the value of the application of neuroendoscopy techniques in the treatment of ventriculoperitoneal (VP) shunt blockage. METHODS: Our study included 3 plans for revision surgeries for VP shunt blockage. In plan A, the choroid plexus or ependyma growing inside the ventricular catheter was completely removed. In plan B, the terminal part of the ventricular catheter was clipped and removed. In plan C, the ventricular catheter was carefully extracted with the aid of neuroendoscopy, and the tissues blocking the catheter were removed. The ventricular catheter was then reinserted into the lateral ventricle. RESULTS: The side holes of the tube may be blocked by cerebral tissue, granulation tissue, newly formed blood vessels, choroid plexus, or ependyma. Five patients successfully underwent plan A revision surgery, 8 patients underwent plan B revision surgery, and the remaining 22 patients underwent plan C revision surgery. After the operation, 34 patients experienced relief of symptoms of elevated intracranial pressure. In all patients, the shunt obstruction was resolved. CONCLUSIONS: Neuroendoscopy techniques can be used to reveal the various causes of shunt obstruction. Any attempt to extract the tube should be performed with the aid of a neuroendoscope. The 3 surgical revision strategies for a blocked catheter are described for the first time in the literature. These approaches can reduce the operation time, the incidence of intraventricular hemorrhage, and the risk of infection.
Subject(s)
Neuroendoscopes/statistics & numerical data , Postoperative Complications/surgery , Prosthesis Failure , Reoperation/instrumentation , Ventriculoperitoneal Shunt/adverse effects , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Reoperation/methods , Retrospective Studies , Treatment Outcome , Ventriculoperitoneal Shunt/instrumentation , Young AdultABSTRACT
AIM: We aimed to investigate the importance of early diagnosis and proper management of paradoxical herniation based on the data of 13 patients who had 14 occurrences of paradoxical herniation. MATERIAL AND METHODS: The characteristics and the effectiveness of treatments of 13 patients with paradoxical herniation were reviewed and analyzed retrospectively. RESULTS: Paradoxical herniation occurred in eight patients (61.54%) during the postoperative 2 weeks and they presented with typical symptoms of brain herniation and a tense skin flap without sinking at the region of decompressive craniectomy. On the other hand, six patients developed paradoxical herniation in the postoperative period of 2 weeks to 2 months and presented with sinking skin flaps and delayed neurological deficits. Furthermore, all patients received emergency treatments, including sufficient hydration, clamping cerebrospinal fluid (CSF) drainage, and being placed in the Trendelenburg position. Six patients achieved full neurologic recovery after successful cranioplasty. CONCLUSION: Intracranial hypotension causing paradoxical herniation can rapidly progress, especially along with CSF depletion. It is important for neurosurgeons to suspect paradoxical herniation in a subset of patients with large cranium defects and tense skin flap without sinking during the postoperative 2 weeks. Paradoxical herniation is rapidly reverted by improving CSF hydration, and performing early cranioplasty referred as the definitive treatment.
