Primary pulmonary osteosarcoma (PPOS) is an extremely rare extraskeletal osteosarcoma. Because its clinical and radiological features are nonspecific, establishing a diagnosis is challenging. We report the case of a 58-year-old man who presented with a 1-month history of cough and 5 days of dyspnea. Initial chest computed tomography showed destructive changes in the left lung and an endobronchial lesion in the left main bronchus. To relieve airway obstruction and obtain diagnostic tissue, a sequential strategy of bronchial artery embolization followed by bronchoscopic electrosurgical snare resection was used. Pathological examination showed a high-grade sarcoma with characteristic malignant osteoid matrix, chondroid differentiation, and numerous multinucleated tumor giant cells. Immunohistochemistry showed positivity for SATB2 and vimentin, with a Ki-67 proliferation index of approximately 30%. Whole-body bone scintigraphy, brain magnetic resonance imaging, and contrast-enhanced abdominal and pelvic computed tomography excluded a primary bone tumor and extrapulmonary metastasis, supporting the diagnosis of PPOS. After the procedure, dyspnea improved, follow-up chest computed tomography showed partial re-expansion of the left lung and disappearance of the left main bronchial lesion, and the patient was referred to a higher-level hospital for radiotherapy. He remained alive at 9-month follow-up after diagnosis. This case suggests that bronchial artery embolization-assisted bronchoscopic electrosurgical snare resection may provide a minimally invasive option for obtaining diagnostic tissue and relieving airway obstruction in selected hypervascular endobronchial tumors.

Background Malignant primary osseous neoplasms of the spine and sacropelvis are rare tumors whose outcomes rely heavily on specialized, guideline-driven care, which is concentrated in metropolitan referral centers. Investigations of rurality in this population have been limited by single-histology cohorts, small numbers of rural patients, and unadjusted comparisons, and none have weighed geographic disadvantage directly against the socioeconomic conditions with which it coexists. This study aimed to determine whether rural residence is independently associated with overall survival and cause-specific survival, and secondarily whether county-level median household income is independently associated with survival in the same models. Methodology This was a retrospective, population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2023. Patients with microscopically confirmed malignant chordoma, chondrosarcoma, osteosarcoma, or Ewing sarcoma of the vertebral column or the pelvic bones, sacrum, or coccyx with known survival time were included. Rurality was defined using SEER county attributes, with nonmetropolitan counties classified as rural. Multivariable Cox proportional hazards models for overall survival and cause-specific survival were adjusted for demographic, socioeconomic, tumor, and treatment characteristics, with time-based interaction terms added where Schoenfeld residuals indicated violation of the proportional hazards assumption. Results Of 3,631 patients (median age = 51 years; 59% male), 3,255 (90%) resided in urban counties and 376 (10%) in rural counties. Rural residence was concentrated in low-income counties (54% below $60,000 vs. 4.1% of urban patients). Rurality was not independently associated with overall survival (hazard ratio (HR) = 0.95, 95% CI (confidence interval) = 0.82-1.09; p = 0.449) or cause-specific survival (HR = 0.94, 95% CI = 0.80-1.11; p = 0.457). County income showed a graded association with overall survival relative to counties below $60,000, with HRs of 0.82 ($80,000-$100,000), 0.72 ($100,000-$120,000), and 0.68 (>$120,000), all with p-values <0.001, and no difference for $60,000-$80,000 (HR = 1.01). A similar gradient was observed for cause-specific survival. Surgery was associated with lower mortality (overall survival: HR = 0.76; cause-specific survival: HR = 0.80; both p < 0.001), whereas radiotherapy was not. Unadjusted differences by rurality in stage at presentation and treatment receipt were small. Conclusions Rural residence conferred no independent survival disadvantage once socioeconomic and clinical factors were accounted for, whereas county-level income remained independently associated with mortality in a graded fashion. Because rural residence and low county income overlap heavily in this cohort, the survival signal appears to be carried by socioeconomic context rather than by geography. These tumors are rare, are not amenable to screening, and are largely managed at specialized referral centers, which may explain the absence of the rural disadvantage described for screen-detectable cancers. Identifying at-risk patients by geography alone may overlook socioeconomically disadvantaged patients in urban counties, and direct assessment of financial and access-related barriers may be more informative than rural-urban classification.

Cell cycle transitions are driven by cyclins in complex with cyclin-dependent kinases (CDK). Here, we demonstrate that cyclin B3, an evolutionarily divergent B-type cyclin previously thought to function exclusively in female meiosis, is expressed in mitotic cells and interacts with both CDK1 and CDK2. We show that cyclin B3-CDK1/2 is essential for timely mitotic progression by ensuring proper chromosome alignment and stable kinetochore-microtubule interactions, while its overexpression accelerates mitosis and improves chromosome alignment kinetics. Through phospho-mass spectrometry, we identify several kinetochore and mitotic spindle components as substrates of cyclin B3-CDK1/2 in mitosis. Notably, cyclin B3 depletion disrupts mitotic progression in most cancer cell lines tested - including colorectal, osteosarcoma, and breast cancer models - while non-transformed cells are largely unaffected. These findings identify cyclin B3-CDK1/2 as a novel driver of mitotic progression and reveal a preferential dependency in a subset of cancer cells that may represent a potential therapeutic vulnerability.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the cell invasion assay data shown in Figs. 2A and 5A on p. 107 and p. 100 respectively, the '0 µM gambogic acid (GA)' data panel in Fig. 2A (upper left panel) contained overlapping sections of data with the 'SiRNA TIMP‑1' and the 'SiRNA + GA (1 µM)' data panels in Fig. 5A; furthermore, upon analyzing the data in this paper independently in the Editorial Office, it came to light that the '0 µM GA' and the '0.5 µM GA' data panels in Fig. 2A also contained an overlapping edge of data, suggesting that these data, which were intended to show the results from differently performed experiments, had apparently been derived from a smaller number of original sources. The authors have been contacted by the Editorial Office to offer an explanation for the apparently incorrect assembly of this pair of figures, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 31: 105‑112, 2013; DOI: 10.3892/ijmm.2012.1192].

A novel electrochemical immunosensor was designed for the ultrasensitive and selective detection of osteocalcin (OCN) normally overexpressed by osteosarcoma cells. The immunosensing was performed using anti-osteocalcin antibody (anti-OCN) modified probe along with a bio-conjugate, where the probe was fabricated by the covalent assembly of anti-OCN with conducting polymer poly-o-aminobenzoic acid (poly-o-ABA) formed over a layer of gold nanostar (AuNS). Bio-conjugates comprised of hydrazine (Hyd) along with anti-OCN was covalently immobilized on citrate capped AuNPs, reveals the immunoreaction at the sensor probe, where Hyd in bioconjugate was used to reduce hydrogen peroxide for direct signal amplification. The osteocalcin was quantitively analyzed using cyclic voltammetry. This technique exhibited an excellent diagnosis tool for the sensitive and selective detection of OCN, and shows broad dynamic range 2 to 64 ng mL[-1] with the detection limit of 0.19 ng mL[-1]. More importantly, it could distinguish osteocalcin from normal and other cancerous proteins, which indicated the promising applications in clinical diagnosis and treatment of osteosarcoma.

DNA2 is a combined nuclease and helicase that processes long 5' flaps and other structures that occur during DNA replication and repair. Current models invoke an essential function of DNA2 in processing stalled replication forks to dampen toxic recombination based restart. As an essential replication stress response factor, DNA2 has been proposed as an anti-cancer drug target with several tool compounds developed. Here we sought to model inhibited DNA2 states using dominant genetics with separation-of-function alleles to identify the optimal mechanisms for DNA2 targeting. We find that expression of DNA2 nuclease-dead alleles exert dominant effects on fitness and DNA damage repair that are dependent on its helicase and RPA binding activities. These mutants are retained on chromatin, suggesting a protein trapping mechanism, perhaps associated with extensive helicase activity. Furthermore, we find an imperfect but interesting link wherein a subset of ALT tumor models are hypersensitive to the presence of DNA2-nuclease dead protein. Together, our data suggests that selectively targeting the nuclease activity of DNA2 in particular cancers may be an effective therapeutic strategy through a protein trapping mechanism.

While recent research has increasingly focused on the role of fibroblasts and macrophages in osteosarcoma, the tumor vasculature remains poorly understood, particularly in metastatic disease. To address this gap, we performed single-nuclei multi-ome (RNA+ATAC) sequencing on 24 human metastatic osteosarcoma specimens. We found that endothelial cells adopt a hybrid endothelial-mesenchymal state resembling endothelial-to-mesenchymal transition (EndMT) and that a subset of diploid endothelial cells expresses osteoblastic transcriptional profiles and gene regulatory networks (GRN). Joint copy-number analysis further identified osteosarcoma cells with endothelial transcriptional programs and GRNs, consistent with vascular mimicry. In vitro assays and syngeneic lineage-tracing experiments validated that tumor educated endothelial cells acquire osteoblast-like features. Together, these findings reveal substantial plasticity among endothelial and osteosarcoma cells in human and murine metastatic osteosarcoma, provide new insight into the how the metastatic microenvironment shapes the tumor vasculature, and challenge current models of osteosarcoma biology.