In our osteosarcoma patient population, (18)F-FDG PET/CT indices (either combined metabolic/volumetric or metabolic indices) determined after neoadjuvant chemotherapy were useful in predicting tumour responses. This held true after only one chemotherapy course.
While transcription as regulated by histones and their post-translational modifications has been well described, the function of histone variants in this process remains poorly characterized. Potentially important insight into this process pertain to the frequently occurring mutations of H3.3, leading to G34 substitutions in childhood glioblastoma and giant cell tumor of the bone (GCTB). In this study, we have established primary cell lines from GCTB patients and used them to uncover the influence of H3.3 G34W substitutions on cellular growth behavior, gene expression, and chromatin compaction. Primary cell lines with H3.3 G34W showed increased colony formation, infiltration and proliferation, known hallmarks of tumor development. Isogenic cell lines with H3.3 G34W recapitulated the increased proliferation observed in primary cells. Transcriptomic analysis of primary cells and tumor biopsies revealed slightly more downregulated gene expression, perhaps by increased chromatin compaction. We identified components related to splicing, most prominently hnRNPs, by immunoprecipitation and mass spectrometry that specifically interact with H3.3 G34W in the isogenic cell lines. RNA-sequencing analysis and hybridization-based validations further enforced splicing aberrations. Our data uncover a role for H3.3 in RNA processing and chromatin modulation that is blocked by the G34W substitution, potentially driving the tumorigenic process in GCTB.
Background and Objectives
The three‐dimensional (3D)‐printed bone tumor resection guide can be personalized for a specific patient and utilized for bone tumor surgery. It is noninvasive, eidetic, and easy to use. We aimed to categorize the use of the 3D‐printed guide and establish in vivo accuracy data.
Methods
We retrospectively reviewed 12 patients, who underwent limb salvage surgery using the 3D‐printed guide at a single institution. To confirm the achievement of a safe bone margin, we compared the actual and planned distances between the cutting surface and tumor, which were reported in the final pathological report and measured from the same virtual cutting plane using graphical data of the cutting guide design, respectively.
Results
The use of the 3D‐printed guide was categorized as follows: (a) wide excision only, (b) wide excision and biological reconstruction with a structural bone allograft shaped in accordance with the 3D‐printed guide, and (c) wide excision and reconstruction with a 3D‐printed personalized implant. The maximal cutting error was 3 mm.
Conclusions
The 3D‐printed resection guide is easy to use and shows promise in the field of orthopedic oncology, with its application in bone tumor resection and reconstruction with a structural bone allograft or 3D‐printed implant.
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