Intracranial solitary fibrous tumor with delayed symptomatic metastasis to the lumbar spine: illustrative case.

BACKGROUND: Intracranial solitary fibrous tumors (SFTs), formerly known as hemangiopericytomas, are rare, aggressive mesenchymal extra-axial tumors typically treated via resection, often with preoperative embolization and postoperative radiation and/or antiangiogenic therapy. Although surgery confers a significant survival benefit, local recurrence and distant metastasis are not uncommon and may occur in a delayed fashion. OBSERVATIONS: The authors describe the case of a 29-year-old male who initially presented with headache, visual disturbance, and ataxia, and was found to have a large right tentorial lesion with mass effect on surrounding structures. He underwent tumor embolization and resection with gross total resection achieved and pathology consistent with World Health Organization grade 2 hemangiopericytoma. The patient recovered well, but 6 years later presented with low back pain and lower extremity radiculopathy and was found to have metastatic disease within the L4 vertebral body causing moderate central canal stenosis. This was successfully treated with tumor embolization followed by spinal decompression and posterolateral instrumented fusion. Metastasis of intracranial SFT to vertebral bone is exceedingly rare. To our knowledge this is only the 16th reported case. LESSONS: Serial surveillance for metastatic disease is imperative in patients with intracranial SFTs given their propensity and unpredictable time course for distant spread.

Site-Specific Bioconjugation through Enzyme-Catalyzed Tyrosine-Cysteine Bond Formation.

The synthesis of protein-protein and protein-peptide conjugates is an important capability for producing vaccines, immunotherapeutics, and targeted delivery agents. Herein we show that the enzyme tyrosinase is capable of oxidizing exposed tyrosine residues into o-quinones that react rapidly with cysteine residues on target proteins. This coupling reaction occurs under mild aerobic conditions and has the rare ability to join full-size proteins in under 2 h. The utility of the approach is demonstrated for the attachment of cationic peptides to enhance the cellular delivery of CRISPR-Cas9 20-fold and for the coupling of reporter proteins to a cancer-targeting antibody fragment without loss of its cell-specific binding ability. The broad applicability of this technique provides a new building block approach for the synthesis of protein chimeras.

Efficient genome editing in the mouse brain by local delivery of engineered Cas9 ribonucleoprotein complexes.

We demonstrate editing of post-mitotic neurons in the adult mouse brain following injection of Cas9 ribonucleoprotein (RNP) complexes in the hippocampus, striatum and cortex. Engineered variants of Cas9 with multiple SV40 nuclear localization sequences enabled a tenfold increase in the efficiency of neuronal editing in vivo. These advances indicate the potential of genome editing in the brain to correct or inactivate the underlying genetic causes of neurological diseases.