Case Report: Successful Use of BRAF/MEK Inhibitors in Aggressive BRAF-mutant Craniopharyngioma.

BACKGROUND: Although a benign intracranial tumor, craniopharyngioma treatment has always been considered a challenging clinical problem. Recently, BRAF V600E mutation in the pathogenesis of papillary craniopharyngioma (PCP) has been further revealed. Thus, BRAF inhibitors (BRAFi) serve as an applicable treatment for patients with PCP. METHODS: Two patients with recurrent PCP were treated with combined BRAFi dabrafenib (150 mg, orally twice daily) and MEK inhibitors (MEKi) trametinib (2 mg, orally twice daily). A follow-up exceeding 2 years was conducted. We meticulously scrutinized the treatment's safety and efficacy profiles by delving into existing literature. RESULTS: One patient harboring a solid tumor achieved a complete tumor response devoid of any adverse events and encountered no recurrence over 2 years subsequent to discontinuation. Moreover, within a mere month of commencing targeted therapy, the tumor demonstrated observable shrinkage. This finding substantiates the considerable potential inherent in targeted therapy for PCP cases marked by the somatic BRAF V600E mutation. CONCLUSIONS: Under specific conditions, individuals diagnosed with PCP can attain a complete tumor response following combined treatment with BRAFi/MEKi.

Expression and clinical significance of VISTA, B7-H3, and PD-L1 in glioma.

Immune checkpoint (IC) therapy has led to a breakthrough in cancer treatment. However, the interaction of ICs is controversial in glioma. We detected features of ICs using transcriptome data and a multicolor immunofluorescence assay. We discovered that B7-H3 increased with grade and age and predicted worse overall survival (OS) at the transcriptional and proteomic levels. VISTA and PD-L1 were associated with OS and grade at the RNA level. At the protein level, VISTA was primarily expressed in tumor cells and TAMs. B7-H3 and VISTA were positively correlated with PD-L1. There was a strong correlation between PD-L1 and CD3 and between VISTA and IBA-1. PD-L1 was coexpressed with T cells. VISTA was coexpressed with TAMs. In T cells, we found a strong correlation in ICs, which worsened in TAMs and tumor cells. In conclusion, B7-H3 is a vital prognostic target for immunotherapy. We provided a potential mechanism for the immunosuppressive microenvironment in glioma.

Preparation and properties of g-TTCP/PBS nanocomposites and its in vitro biocompatibility assay.

In an effort to decrease the aggregation of tetracalcium phosphate (TTCP, Ca4(PO4)2O) in composites and develop better bone substitute materials, a series of poly(l-lactic acid) (PLLA)-grafted TTCP (g-TTCP) particles were prepared by a ring-opening polymerization with l-lactide (the monomer for synthesizing PLLA) in the presence of catalyst stannous octoate [Sn(Oct)2]. The g-TTCP/poly(1,4-butylene succinate) (PBS) composites with the different g-TTCP contents were prepared via melting processing. The bonding between the PLLA and the TTCP particles was analyzed by FTIR, TG, (1)H NMR and XPS. The results confirmed that the PLLA was grafted on the surface of the TTCP particles. Time-dependent phase monitoring indicated that the g-TTCP had enhanced dispersion in the PBS solution. Water contact angle measurement and cell culture were also used to investigate the properties of the g-TTCP/PBS composites. The g-TTCP in composites provided more favorable environments for rat osteoblast to attach and grow on the surface of the g-TTCP/PBS composites. Cell proliferated well in the extracted solution of the g-TTCP/PBS composites with different g-TTCP content, and there was no necrotic or suspended cells appeared.