Integrated proteogenomic characterization of glioblastoma evolution.

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention.

Fusion rate of Escherichia coli-derived recombinant human bone morphogenetic protein-2 compared with local bone autograft in posterior lumbar interbody fusion for degenerative lumbar disorders.

BACKGROUND CONTEXT: The use of recombinant human bone morphogenetic proteins-2 (rhBMP-2) for spinal fusion has been reported to be effective. However, most studies have focused on posterolateral and anterior lumbar interbody fusion, and few have investigated posterior lumbar interbody fusion (PLIF). PURPOSE: This study aimed to determine the effectiveness and safety of the delivery of Escherichia coli-derived rhBMP-2 (E.BMP-2) with hydroxyapatite (HA) and ß-tricalcium phosphate (ß-TCP) poloxamer hydrogel composite carriers for PLIF. STUDY DESIGN: A retrospective study. PATIENT SAMPLE: Patients who underwent 1 to 3 levels of PLIF for lumbar degenerative disc disorders between 2015 and 2020 with a follow-up of ≥1 year were enrolled. In total, 254 patients (357 levels) were included in the analysis. The evaluation was performed at each segment level. In the E.BMP-2 group, 160 patients (221 levels) received autologous local bone with E.BMP-2 (maximum 0.5 mg/level), and in the control group, 94 patients (136 levels) received only local bone graft. OUTCOME MEASURES: The primary outcome of this study was to compare the X-ray and CT fusion rates between the two groups. Secondary outcomes included analysis of the patients' clinical outcomes and postoperative complications on CT scans. METHODS: Clinical evaluations were performed using a visual analog scale for back pain, the Oswestry Disability Index for disability, and physical and mental component summaries of the Short Form 36-Item Form Health Survey to assess functional effects and quality of life. The fusion was evaluated using radiography and CT. On radiography, solid fusion was defined when the difference between extension and flexion was less than 5°. On CT, solid fusion was defined when the upper and lower vertebral bodies were connected by the trabecular bone (bone bridge formation). In addition, complications such as osteolysis, cage subsidence, and screw loosening were investigated using CT. RESULTS: All clinical results for low back pain, disability, and quality of life in both groups were excellent and showed statistically significant improvements compared with baseline (p<.0001). According to the X-ray evaluations, fusion was achieved in 92.31% (204/221) of the patients in the E.BMP-2 group and 82.35% (112/136) of the patients in the control group (p=.0041). According to the CT evaluations, the fusion rates were 93.21% (206/221) and 88.24% (120/136) in the E.BMP-2 and control groups (p=.1048), respectively. Except for screw loosening, which had a significantly higher incidence in the control group (p=.0014), the rates of most postoperative complications were not significantly different between the groups. CONCLUSIONS: This study demonstrated that the adjunctive use of a low dose of E.BMP-2 with HA and ß-TCP hydrogel can effectively promote bone fusion, making it a promising option for patients with limited autograft availability or compromised bone quality in PLIF.

What Affects Segmental Lordosis of the Surgical Site after Minimally Invasive Transforaminal Lumbar Interbody Fusion?

PURPOSE: This study was undertaken to identify factors that affect segmental lordosis (SL) after minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) by comparing patients whose postoperative SL increased with those whose decreased. MATERIALS AND METHODS: Fifty-five patients underwent MIS-TLIF at our institute from January 2018 to September 2019. Demographic, pre- and postoperative radiologic, and cage-related factors were included. Statistical analyses were designed to compare patients whose SL increased with decreased after surgery. RESULTS: After surgery, SL increased in 34 patients (group I) and decreased in 21 patients (group D). The index level, disc lordosis, SL, lumbar lordosis, proximal lordosis (PL), and Y-axis position of the cage (Yc) differed significantly between groups I and D. The cage in group I was more anterior than that in group D (Yc: 55.84% vs. 51.24%). Multivariate analysis showed that SL decreased more significantly after MIS-TLIF when the index level was L3/4 rather than L4/5 [odds ratio (OR): 0.46, p=0.019], as preoperative SL (OR: 0.82, p=0.037) or PL (OR: 0.68, p=0.028) increased, and as the cage became more posterior (OR: 1.10, p=0.032). CONCLUSION: Changes in SL after MIS-TLIF appear to be associated with preoperative SL and PL, index level, and Yc. An index level at L4/5 instead of L3/4, smaller preoperative SL or PL, and an anterior position of the cage are likely to result in increased SL after MIS-TLIF.