Journal of Bone Oncology最新文献_第2页

Doxorubicin induces bone loss and modifies multiple cell populations in vivo – Implications for modelling of bone metastasis 阿霉素诱导骨丢失并改变体内多个细胞群-骨转移模型的意义

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2026-02-01 Epub Date: 2025-12-13 DOI: 10.1016/j.jbo.2025.100736

Veli Kaan Aydin , Lubaid Saleh , Penelope Dawn Ottewell , Ingunn Holen

Doxorubicin (DOX), commonly used to treat breast cancer, is associated with cardiotoxicity and has negative effects on other organ systems, including the skeleton. DOX-induced bone damage has been demonstrated in murine models; however, results are conflicting due to the use of different doses, schedules, and rat/mouse strains. As DOX is used to limit tumour progression in models of skeletal metastasis, it is paramount to determine how the agent affects the bone microenvironment in the relevant mouse strains, to enable correct interpretation of DOX effects in tumour studies. We have therefore investigated the effects of DOX on bone structure and a range of bone and bone marrow cell populations, comparing immunocompetent and immunocompromised mice.

Groups of 7-week-old female BALB/c and BALB/c Nude mice were treated with either saline (control), 4 or 6 mg/kg DOX weekly for four weeks. Effects on bone volume and structure was determined using ex vivo µCT, a panel of bone marrow cell populations were quantified by flow cytometry and osteoblast/osteoclast numbers were assessed using bone histomorphometry.

DOX caused trabecular bone loss, with immunocompetent BALB/c mice being more sensitive to DOX than the immunocompromised BALB/c nude counterparts. The 6 mg/kg dose of DOX altered the ratio of bone marrow immune and haematopoietic cell populations in both groups, increasing the numbers of hematopoietic cells and progenitors, decreasing B cells and increasing the number of neutrophils. Bone marrow macrophage and monocyte numbers were increased following DOX treatment in BALB/c nude mice only. Our data demonstrate that DOX impacts a number of cell types in the bone microenvironment, highlighting the importance of considering treatment-induced bone effects when using DOX in models of bone metastasis.

多柔比星（DOX）通常用于治疗乳腺癌，与心脏毒性有关，并对包括骨骼在内的其他器官系统产生负面影响。dox诱导的骨损伤已在小鼠模型中得到证实；然而，由于使用不同的剂量、时间表和大鼠/小鼠品系，结果是相互矛盾的。由于DOX在骨骼转移模型中用于限制肿瘤进展，因此确定药物如何影响相关小鼠品系的骨微环境是至关重要的，以便在肿瘤研究中正确解释DOX的作用。因此，我们研究了DOX对骨结构和一系列骨和骨髓细胞群的影响，比较了免疫功能正常和免疫功能低下的小鼠。将7周龄雌性BALB/c和BALB/c裸鼠分别给予生理盐水（对照）、4或6 mg/kg DOX，每周治疗4周。用离体微CT检测对骨体积和结构的影响，用流式细胞术定量骨髓细胞群，用骨组织形态术评估成骨细胞/破骨细胞数量。DOX引起骨小梁丢失，免疫功能正常的BALB/c小鼠比免疫功能受损的BALB/c裸小鼠对DOX更敏感。6mg /kg剂量的DOX改变了两组骨髓免疫细胞和造血细胞群的比例，增加了造血细胞和祖细胞的数量，减少了B细胞，增加了中性粒细胞的数量。仅在BALB/c裸小鼠中，DOX处理后骨髓巨噬细胞和单核细胞数量增加。我们的数据表明，DOX影响骨微环境中的多种细胞类型，强调了在骨转移模型中使用DOX时考虑治疗诱导的骨效应的重要性。

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引用次数: 0

Real-life use of bone-targeting agents for bone metastases in France between 2009 and 2018: Results of the OPTIMOS study 2009年至2018年间，法国骨转移的骨靶向药物的实际使用：OPTIMOS研究结果

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2026-02-01 Epub Date: 2026-01-04 DOI: 10.1016/j.jbo.2025.100738

Cyrille B. Confavreux , Béatrice Bouvard , Nicolas Girard , Pauline Bosco-Levy , Clarisse Marchal , Maeva Nolin , Eric Lehmann , Gaelle Desameric , Manon Belhassen

Aim

To determine the use of bone-targeting agents (BTAs) in clinical practice in France and the occurrence of skeletal-related events (SREs) in cancer patients with bone metastases.

Methods

This study analysed data, recorded prospectively in a French National Health Insurance database, for patients who had a first diagnosis of bone metastases between 2009 and 2018.

Results

A total of 6,663 patients were analysed (mean age 69.7 ± 13.2 years, 53.2 % male) corresponding to 2,363 bone metastases only patients and 4,300 patients with SREs at inclusion. The most frequent primary cancers were breast (15.8 %), prostate (13.4 %), lung (12.6 %) and digestive cancer (10.6 %). Six-hundred and twenty-one patients (9.3 %) were treated with BTAs (52.7 % with denosumab). Median [IQR] time between inclusion and BTA initiation was similar with denosumab (3.3 months [1.2–7.9]) and bisphosphonates (3.3 months [1.2–8.7]). Patients with a SRE at inclusion and early BTA initiation (≤3 months) had a significative lower incidence of a second SRE at 12 months than those with late initiation (13.6 % [95 %CI: 8.1–20.4] vs. 21.6 % [14.8–29.2] respectively; p < 0.001).

Conclusion

BTAs are underused in bone metastases patients in France. There is an urgent need to optimise bone metastases management in accordance with ESMO 2020 guidelines.

目的了解骨靶向药物（bone-targeting agents, BTAs）在法国临床中的使用情况及骨转移癌患者骨相关事件（bone- relevant events, SREs）的发生情况。方法：本研究分析了2009年至2018年间首次诊断为骨转移的患者在法国国民健康保险数据库中前瞻性记录的数据。结果共纳入6663例患者（平均年龄69.7±13.2岁，男性53.2%），其中仅骨转移患者2363例，合并SREs患者4300例。最常见的原发癌症是乳腺癌（15.8%）、前列腺癌（13.4%）、肺癌（12.6%）和消化道癌（10.6%）。621例患者（9.3%）接受bta治疗（52.7%接受denosumab治疗）。denosumab（3.3个月[1.2-7.9]）和双膦酸盐（3.3个月[1.2-8.7]）的纳入和BTA起始之间的中位[IQR]时间相似。在纳入和早期BTA开始（≤3个月）时发生SRE的患者在12个月时发生第二次SRE的发生率显著低于开始较晚的患者（分别为13.6% [95% CI: 8.1-20.4]和21.6% [14.8-29.2];p < 0.001）。结论bta在法国骨转移患者中的应用不足。根据ESMO 2020指南，迫切需要优化骨转移管理。

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引用次数: 0

Pilot study of separation surgery with intraoperative radiotherapy (IORT) for spine metastasis 分离手术联合术中放疗治疗脊柱转移的初步研究

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2026-02-01 Epub Date: 2025-12-19 DOI: 10.1016/j.jbo.2025.100737

Baiyi Liu , Dongsheng Wang , Jian Zhang , Bo Huang , Mingying Geng , Peng Liu , Yaoyao Liu

Objective

This study aimed to introduce a novel modified separation surgery combined with intraoperative radiotherapy (MSS-IORT) treatment strategy for spinal metastasis and evaluate its efficacy and safety.

Methods

A prospective study was conducted from January 2023 to June 2024. Patients with spinal metastasis exhibiting epidural spinal cord compression (ESCC) ≥ 2 grades and spinal instability neoplastic score (SINS) ≥ 7 were enrolled and underwent MSS-IORT. During the procedure, a dose of 8–10 Gy of IORT was administered to the tumor-invaded vertebrae segments during modified separation surgery. Pain intensity was assessed using the visual analog scale (VAS) preoperatively and at 1 week, 3 months, 6 months, and 12 months postoperatively. Neurological function was evaluated via the Frankel grade system, and functional status was measured using the Karnofsky performance scale (KPS) preoperatively and at 3, 6, and 12 months after surgery. Local control was evaluated based on X-ray, CT, or MRI examination. Survival time and perioperative complications were also documented.

Results

A total of 38 patients (median age: 60 years) with 46 involved vertebrae were treated with MSS-IORT. The mean operation time was 277.5 min, and the mean blood loss was 750 ml. After a mean follow-up of 174.5 days, the VAS score decreased significantly postoperatively and continued to decline over time. The KPS score increased significantly at 6 and 12 months, and the Frankel grade significantly improved at 12 months. Local control failure occurred in 3 patients, and 13 experienced adverse events without IORT.

Conclusion

The MSS-IORT strategy demonstrates both safety and efficacy, representing a promising treatment option for spine metastases, particularly in patients with ESCC grades ≥ 2 and SINS ≥ 7.

目的介绍一种新的改良分离手术联合术中放疗（MSS-IORT）治疗脊柱转移的策略，并评价其疗效和安全性。方法于2023年1月至2024年6月进行前瞻性研究。纳入硬膜外脊髓压迫(ESCC)≥2级、脊柱不稳定肿瘤评分(SINS)≥7级的脊髓转移患者，并进行MSS-IORT。在手术过程中，在改良分离手术中，对肿瘤侵入的椎节段给予8-10 Gy的IORT剂量。术前、术后1周、3个月、6个月、12个月采用视觉模拟评分法（VAS）评估疼痛强度。术前、术后3、6、12个月采用Frankel评分系统评估神经功能，并采用Karnofsky性能量表（KPS）测量功能状态。根据x线、CT或MRI检查评估局部控制情况。并记录了生存时间和围手术期并发症。结果38例患者（中位年龄60岁），46个受累椎接受MSS-IORT治疗。平均手术时间277.5 min，平均失血量750 ml。平均随访174.5 d，术后VAS评分明显下降，且随时间持续下降。KPS评分在6个月和12个月时显著升高，Frankel评分在12个月时显著提高。3例发生局部控制失败，13例发生不良事件，未进行IORT。结论MSS-IORT策略具有安全性和有效性，是一种有希望的脊柱转移治疗选择，特别是对于ESCC≥2级和SINS≥7级的患者。

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引用次数: 0

Mri-based habitat and peritumoral radiomics for predicting the proliferative activity of stromal cells in giant cell tumor of bone 基于mri的栖息地和肿瘤周围放射组学预测骨巨细胞瘤中基质细胞的增殖活性

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2026-02-01 Epub Date: 2025-12-08 DOI: 10.1016/j.jbo.2025.100733

Jie Xia , Kunming Jiang , Jinyi Zhou , Lei Cao , Fan Xiao , Jingxuan Jiang

Purpose

This study aims to explore the feasibility of MRI-based habitat and peritumoral radiomics for predicting the proliferative activity of stromal cells in giant cell tumor of bone (GCTB).

Material and methods

A retrospective study was performed on 133 patients (102 in training cohort and 31 in validation cohort) diagnosed with GCTB from four centers. The tumor was meticulously segmented into three distinct habitat subregions using K-means clustering, incorporating a 1-pixel peritumoral expansion to capture the microenvironments surrounding the tumor. After feature extraction and selection, habitat, intratumoral and peritumoral models integrating three different machine learning classifiers were constructed respectively to identify GCTB patients with high and low proliferation. The performance of the models was assessed by receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). SHAP analysis was utilized to enhance model interpretability.

Results

Among the eligible patients, 43 (32.3 %) diagnosed with high proliferative activity of stromal cells in GCTB by pathological diagnosis. Among all models tested in the validation cohort, the Logistic Regression (LR) algorithm for habitat model exhibited superior performance in the validation cohort (AUC: 0.956, 95 % CI: 0.887–1.000). The calibration curves and DCA exhibited fit for the habitat model while providing great clinical net benefit.

Conclusion

MRI-based habitat radiomics had the potential to predict the proliferative activity of stromal cells in GCTB. This model may help determine optimal treatment strategies and improve patient outcomes.

目的探讨mri栖息地和瘤周放射组学预测骨巨细胞瘤（GCTB）基质细胞增殖活性的可行性。材料与方法对来自4个中心的133例确诊为GCTB的患者（训练组102例，验证组31例）进行回顾性研究。使用K-means聚类将肿瘤精心分割为三个不同的栖息地亚区，并结合1像素肿瘤周围扩展来捕获肿瘤周围的微环境。经过特征提取和选择，分别构建融合三种不同机器学习分类器的栖息地、肿瘤内和肿瘤周围模型，识别高增殖和低增殖的GCTB患者。通过受试者工作特征（ROC）曲线、校正图和决策曲线分析（DCA）评估模型的性能。利用SHAP分析提高模型的可解释性。结果在符合条件的患者中，43例（32.3%）经病理诊断为GCTB间质细胞高增殖活性。在验证队列的所有模型中，栖息地模型的Logistic回归（LR）算法在验证队列中表现优异（AUC: 0.956, 95% CI: 0.887 ~ 1.000）。校正曲线和DCA均符合生境模型，临床净效益显著。结论基于mri的生境放射组学可预测GCTB基质细胞的增殖活性。该模型可以帮助确定最佳治疗策略并改善患者的预后。

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引用次数: 0

Soft tissue recurrence in giant cell tumor of Bone: A comprehensive review of pathogenesis, imaging features, and clinical management 骨巨细胞瘤的软组织复发：发病机制、影像学特征和临床治疗的综合综述

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-12-01 Epub Date: 2025-11-08 DOI: 10.1016/j.jbo.2025.100725

Khodamorad Jamshidi , Hamed Naghizadeh , Sadegh Saberi , Farshad Zand Rahimi , Aidin Arabzadeh , Seyyed Saeed Khabiri

Background

Giant cell tumor of bone (GCTB) is a benign but locally aggressive neoplasm with a high risk of recurrence. Among its patterns of relapse, soft-tissue recurrence (STR) is an uncommon but clinically significant entity, often presenting as ossified or non-ossified perilesional nodules. Despite its rarity, STR poses diagnostic and therapeutic challenges that require clarification.

Methods

A comprehensive literature review was performed across PubMed, Embase, and Google Scholar from 1980 through January 2025, focusing on the epidemiology, pathogenesis, imaging features, histopathology, management, and outcomes of STR in GCTB. Case reports, series, and retrospective studies explicitly distinguishing STR from intraosseous recurrence were included, and findings were synthesized narratively.

Results

STR occurs in approximately 2–3 % of GCTB cases, typically within 6–12 months after surgery. Major risk factors include curettage procedures, pathological fractures, cortical breaches, and unrecognized microscopic soft-tissue extension. Imaging reveals three distinct patterns: peripheral “eggshell” ossification, central nodular calcification, and purely soft-tissue lesions. Histology mirrors primary GCTB, often with osteogenic metaplasia, while molecular testing confirms retention of H3F3A mutations. Surgical excision with clear margins remains the mainstay of treatment, yielding excellent functional outcomes. However, up to 60 % of patients experience multiple recurrences, highlighting the need for vigilant surveillance. Systemic agents such as denosumab or bisphosphonates remain investigational, and radiotherapy is generally contraindicated due to malignant transformation risk.

Conclusion

STR represents a rare but distinct subset of GCTB recurrences. Awareness of risk factors, early imaging-based detection, and complete surgical excision are critical for optimal outcomes. Further multicenter studies are required to define surveillance protocols, validate molecular predictors, and clarify the role of systemic therapy in this challenging condition.

骨巨细胞瘤（GCTB）是一种良性但局部侵袭性的肿瘤，具有很高的复发风险。在其复发模式中，软组织复发（STR）是一种不常见但临床上重要的实体，通常表现为骨化或非骨化的病灶周围结节。尽管它很罕见，但STR对诊断和治疗提出了挑战，需要澄清。方法对1980年至2025年1月期间PubMed、Embase和谷歌Scholar的文献进行综合分析，重点关注STR在GCTB中的流行病学、发病机制、影像学特征、组织病理学、治疗和结局。病例报告，系列和回顾性研究明确区分STR与骨内复发，并综合叙述结果。结果约2 - 3%的GCTB病例发生str，通常发生在术后6-12个月内。主要的危险因素包括刮除手术、病理性骨折、皮质破裂和显微镜下无法识别的软组织延伸。影像学显示三种不同的模式：周围“蛋壳”骨化，中央结节钙化和纯粹的软组织病变。组织学反映了原发性GCTB，通常伴有成骨化生，而分子检测证实保留了H3F3A突变。手术切除与明确的边界仍然是治疗的主要方式，产生良好的功能结果。然而，高达60%的患者经历多次复发，突出了警惕监测的必要性。全身药物如地诺单抗或双膦酸盐仍在研究中，由于恶性转化的风险，放疗通常是禁忌的。结论str是GCTB复发的一个罕见但独特的子集。意识到危险因素、早期影像学检测和完全手术切除是获得最佳结果的关键。需要进一步的多中心研究来确定监测方案，验证分子预测因子，并阐明全身治疗在这种具有挑战性的疾病中的作用。

{"title":"Soft tissue recurrence in giant cell tumor of Bone: A comprehensive review of pathogenesis, imaging features, and clinical management","authors":"Khodamorad Jamshidi , Hamed Naghizadeh , Sadegh Saberi , Farshad Zand Rahimi , Aidin Arabzadeh , Seyyed Saeed Khabiri","doi":"10.1016/j.jbo.2025.100725","DOIUrl":"10.1016/j.jbo.2025.100725","url":null,"abstract":"<div><h3>Background</h3><div>Giant cell tumor of bone (GCTB) is a benign but locally aggressive neoplasm with a high risk of recurrence. Among its patterns of relapse, soft-tissue recurrence (STR) is an uncommon but clinically significant entity, often presenting as ossified or non-ossified perilesional nodules. Despite its rarity, STR poses diagnostic and therapeutic challenges that require clarification.</div></div><div><h3>Methods</h3><div>A comprehensive literature review was performed across PubMed, Embase, and Google Scholar from 1980 through January 2025, focusing on the epidemiology, pathogenesis, imaging features, histopathology, management, and outcomes of STR in GCTB. Case reports, series, and retrospective studies explicitly distinguishing STR from intraosseous recurrence were included, and findings were synthesized narratively.</div></div><div><h3>Results</h3><div>STR occurs in approximately 2–3 % of GCTB cases, typically within 6–12 months after surgery. Major risk factors include curettage procedures, pathological fractures, cortical breaches, and unrecognized microscopic soft-tissue extension. Imaging reveals three distinct patterns: peripheral “eggshell” ossification, central nodular calcification, and purely soft-tissue lesions. Histology mirrors primary GCTB, often with osteogenic metaplasia, while molecular testing confirms retention of H3F3A mutations. Surgical excision with clear margins remains the mainstay of treatment, yielding excellent functional outcomes. However, up to 60 % of patients experience multiple recurrences, highlighting the need for vigilant surveillance. Systemic agents such as denosumab or bisphosphonates remain investigational, and radiotherapy is generally contraindicated due to malignant transformation risk.</div></div><div><h3>Conclusion</h3><div>STR represents a rare but distinct subset of GCTB recurrences. Awareness of risk factors, early imaging-based detection, and complete surgical excision are critical for optimal outcomes. Further multicenter studies are required to define surveillance protocols, validate molecular predictors, and clarify the role of systemic therapy in this challenging condition.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100725"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

hMSCs-derived exosomal MIR17HG promotes follicular helper T cell differentiation and osteosarcoma progression via the miR-372-3p/BCL6 axis hmscs来源的外泌体MIR17HG通过miR-372-3p/BCL6轴促进滤泡性辅助性T细胞分化和骨肉瘤进展

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-12-01 Epub Date: 2025-11-12 DOI: 10.1016/j.jbo.2025.100726

Jin Qi , Gang Xue , Baomin Wu , Peng Zhu , Yapeng Wang

Background

Osteosarcoma (OS) is a life-threatening malignancy in children and adolescents, with limited treatment options for resistant or metastatic disease. Exosomes derived from hMSCs regulate tumor immunity by transporting molecules such as long non-coding RNA (lncRNA). The lncRNA MIR17HG is known to promote OS progression, yet its role in regulating T follicular helper (Tfh) cell differentiation in OS is unclear. This study is the first to systematically explore how MIR17HG influences Tfh cell differentiation, activation, and OS cell proliferation via the miR-372-3p/BCL6 signaling cascade.

Methods

Exosomes were extracted from hMSCs using differential centrifugation. Characterization of hMSCs-derived exosomes was conducted by TEM, NTA and western blotting. The expression of MIR17HG, BCL6 and PD-1 was determined by qRT‒PCR or western blotting. The differentiation and activation of Tfh cells, as well as OS apoptosis, were assessed through flow cytometry. OS cell viability was determined by a CCK-8 assay. The effect of hMSCs-Exo-MIR17HG on tumors was assessed in an MG63-derived xenograft mouse model. The expression of Ki67 was examined via IHC. RNA immunoprecipitation was performed to validate the interaction between MIR17HG and miR-372-3p. A dual-luciferase reporter assay was performed to explore the correlation between miR-372-3p and BCL6.

Results

The lncRNA MIR17HG was expressed in hMSCs-derived exosomes and upregulated by overexpression. hMSCs-Exo or hMSCs-Exo-MIR17HG promoted the differentiation and activation of Tfh cells, accompanied by increased PD-1 and BCL6 expression in CD4⁺ T cells, which enhanced OS cell proliferation. Furthermore, hMSCs-Exo-MIR17HG exerted a tumor-promoting effect in a CDX mouse model. Mechanistically, the effects driven by MIR17HG were abolished by miR-372-3p overexpression, and BCL6 was identified as a direct functional target of miR-372-3p.

Conclusion

These findings demonstrate that exosomal MIR17HG derived from hMSCs drives the differentiation of follicular helper T cells and the progression of OS via the miR-372-3p/BCL6 axis.

背景：骨肉瘤（OS）是儿童和青少年中一种危及生命的恶性肿瘤，对于耐药或转移性疾病的治疗选择有限。来自hMSCs的外泌体通过运输长链非编码RNA （lncRNA）等分子来调节肿瘤免疫。已知lncRNA MIR17HG可促进OS进展，但其在OS中调节T滤泡辅助细胞（Tfh）分化中的作用尚不清楚。本研究首次系统探讨了MIR17HG如何通过miR-372-3p/BCL6信号级联影响Tfh细胞分化、激活和OS细胞增殖。方法采用差速离心法从hMSCs中提取性体。采用TEM、NTA和western blotting对hmsc衍生外泌体进行表征。采用qRT-PCR或western blotting检测MIR17HG、BCL6、PD-1的表达。流式细胞术观察Tfh细胞的分化、活化及OS的凋亡情况。CCK-8法测定OS细胞活力。在mg63衍生的异种移植小鼠模型中评估了hMSCs-Exo-MIR17HG对肿瘤的影响。IHC检测Ki67的表达。通过RNA免疫沉淀来验证MIR17HG和miR-372-3p之间的相互作用。采用双荧光素酶报告基因检测来探讨miR-372-3p与BCL6之间的相关性。结果lncRNA MIR17HG在hmsc来源的外泌体中表达，并通过过表达上调。hMSCs-Exo或hMSCs-Exo- mir17hg促进Tfh细胞的分化和活化，同时CD4+ T细胞中PD-1和BCL6表达升高，增强OS细胞增殖。此外，hMSCs-Exo-MIR17HG在CDX小鼠模型中具有促肿瘤作用。在机制上，MIR17HG驱动的效应被miR-372-3p过表达消除，BCL6被确定为miR-372-3p的直接功能靶点。结论这些发现表明来自hMSCs的外泌体MIR17HG通过miR-372-3p/BCL6轴驱动滤泡辅助性T细胞的分化和OS的进展。

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引用次数: 0

Benign and malignant bone lesion diagnosis based on self-supervised and radiomics fusion using SPECT/CT images 基于自监督与放射组学融合的SPECT/CT影像良恶性骨病变诊断

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-12-01 Epub Date: 2025-10-31 DOI: 10.1016/j.jbo.2025.100723

Weiming Xie , Xiaozhou Bai , Miao Liu , Haonan Shangguan , Ying Zhan , Xiaodan Wu , Yingxin Dai , Yusong Pei , Guoxu Zhang , Zhiguo Wang , Zhaomin Yao

Purpose

This study aims to improve the diagnostic accuracy of SPECT/CT imaging in distinguishing benign from malignant bone lesions by integrating self-supervised deep learning and radiomics, reducing subjectivity in traditional image interpretation for more reliable clinical decision-making.

Methods

We developed a multi-scale, multi-modal framework combining radiomics with self-supervised learning. The novel SPECT-guided model, SPARC-Net, uses functional SPECT data as semantic priors to extract discriminative features from CT scans without manual annotations. Deep features from SPARC-Net were fused with radiomics to form a unified representation. The model was trained and validated on 741 confirmed bone lesion cases using five-fold cross-validation, with interpretability assessed via Grad-CAM.

Results

The fused model achieved 82.3 % accuracy, 0.890 AUC, 72.3 % F1 score, 79.3 % precision, 66.6 % sensitivity, and 90.7 % specificity, outperforming single-modality models. Grad-CAM confirmed the model focused on metabolically active regions identified by SPECT.

Conclusion

SPARC-Net, integrating SPECT-guided self-supervised learning with CT-based radiomics, improves classification of benign and malignant lesions, enhancing the accuracy, robustness, and interpretability of SPECT/CT imaging for bone tumor diagnosis.

目的本研究旨在通过自我监督深度学习与放射组学的结合，提高SPECT/CT成像对骨良恶性病变的诊断准确率，减少传统图像解读中的主观性，使临床决策更加可靠。方法将放射组学与自监督学习相结合，建立了一个多尺度、多模式的框架。新的SPECT引导模型SPARC-Net使用功能SPECT数据作为语义先验，从CT扫描中提取判别特征，而无需手动注释。将SPARC-Net的深度特征与放射组学融合，形成统一的表示。该模型在741例确诊的骨病变病例中进行了训练和验证，使用五倍交叉验证，并通过Grad-CAM评估了可解释性。结果融合模型的准确率为82.3%，AUC为0.890，F1评分为72.3%，准确率为79.3%，灵敏度为66.6%，特异性为90.7%，优于单一模型。Grad-CAM证实该模型集中于SPECT鉴定的代谢活性区域。结论sparc - net将SPECT引导下的自我监督学习与基于CT的放射组学相结合，改善了良恶性病变的分类，提高了SPECT/CT影像学对骨肿瘤诊断的准确性、稳健性和可解释性。

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引用次数: 0

Multimodal deep learning for bone tumor diagnosis with clinical imaging, pathology, and blood biomarkers 基于临床影像、病理和血液生物标志物的骨肿瘤诊断的多模态深度学习

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-12-01 Epub Date: 2025-10-22 DOI: 10.1016/j.jbo.2025.100718

Hang Sang , Tao Lin , Lincong Luo , Mingrui Liu , Jiaying Li , Xiang Luo , Jianlin Shen , Shizhen Zhong , Lin Xu , Wenhua Huang

Accurate classification of bone tumors as benign, malignant, or intermediate is crucial for patient treatment decisions. Misclassification may result in overtreatment of benign cases or delayed intervention for aggressive tumors, significantly impacting patient prognosis. However, current methods rely heavily on single-modality imaging analysis, making it difficult to handle variable lesion locations and complex cancer types. To address these limitations, we propose a novel multimodal deep learning framework that integrates clinical images, pathological slices, and blood biomarkers for automated bone tumor detection and three-class classification. The framework operates in two stages: first, a YOLOv5-based detection model localizes tumor regions on clinical images. Next, a classification model utilizes ResNet to extract deep features from both the clinical images and pathological slices, while abnormal blood biomarkers are transformed into descriptive text by a large language model and subsequently encoded into semantic features using BioBERT. Finally, features from all three modalities are integrated via a fusion module to capture complementary information and enable accurate tumor classification. The evaluation was performed using two distinct datasets: a clinical imaging dataset for bone tumor detection, and a separate multi-modal cohort comprising clinical imaging, pathology, and blood biomarkers for tumor classification. The detection model demonstrated strong localization capabilities, achieving a test [email protected] of 0.7925. For the classification task, ablation studies validated the complementary contribution of each modality. Notably, our multimodal fusion approach outperformed unimodal baselines, attaining a macro-average precision of 0.9056, F1-score of 0.8736, and AUC of 0.9759 in tumor classification—outperforming existing models.

骨肿瘤的准确分类为良性、恶性或中度对患者的治疗决策至关重要。错误分类可能导致良性病例的过度治疗或侵袭性肿瘤的延迟干预，严重影响患者预后。然而，目前的方法严重依赖于单模态成像分析，难以处理不同的病变位置和复杂的癌症类型。为了解决这些限制，我们提出了一种新的多模态深度学习框架，该框架集成了临床图像、病理切片和血液生物标志物，用于自动骨肿瘤检测和三类分类。该框架分为两个阶段：首先，基于yolov5的检测模型在临床图像上定位肿瘤区域。接下来，分类模型利用ResNet从临床图像和病理切片中提取深层特征，而异常血液生物标志物通过大型语言模型转换为描述性文本，随后使用BioBERT编码为语义特征。最后，通过融合模块整合所有三种模式的特征，以捕获互补信息并实现准确的肿瘤分类。评估使用两个不同的数据集进行：一个用于骨肿瘤检测的临床影像学数据集，以及一个单独的多模式队列，包括用于肿瘤分类的临床影像学、病理学和血液生物标志物。检测模型显示出强大的定位能力，实现了0.7925的测试[email protected]。对于分类任务，消融研究验证了每种模式的互补贡献。值得注意的是，我们的多模态融合方法优于单模态基线，肿瘤分类的宏观平均精度为0.9056，f1评分为0.8736，AUC为0.9759，优于现有模型。

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引用次数: 0

Bone disease burden does not impact overall survival in newly diagnosed patients with multiple myeloma − a single center, retrospective imaging analysis on 119 patients 骨病负担不影响新诊断多发性骨髓瘤患者的总生存率——对119例患者进行单中心回顾性影像学分析

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-12-01 Epub Date: 2025-10-25 DOI: 10.1016/j.jbo.2025.100720

Evangelos Terpos , Vassilis Koutoulidis , Ioannis Ntanasis-Stathopoulos , Stylianos Mavropoulos-Papoudas , Maria Douka , Maria Gavriatopoulou , Panagiotis Malandrakis , Vasiliki Spiliopoulou , Foteini Theodorakakou , Despina Fotiou , Magdalini Migkou , Nikolaos Kanellias , Evangelos Eleutherakis-Papaiakovou , Efstathios Kastritis , Lia-Angela Moulopoulos , Meletios A Dimopoulos

Background

Multiple myeloma (MM) frequently presents with myeloma bone disease (MBD), manifesting as osteolytic lesions and skeletal-related events (SREs), significantly impairing quality of life and increasing morbidity. Whole-body low-dose computed tomography (WBLDCT) has become the standard for assessing bone involvement at diagnosis, but its prognostic significance remains unclear. The aim of this study was to evaluate the burden of MBD in newly diagnosed MM patients using WBLDCT and examined associations between imaging characteristics and survival outcomes.

Methods

In this retrospective, single center, analysis of 119 MM patients, WBLDCT was performed at diagnosis prior to treatment initiation. Imaging findings, including vertebral compression fractures (VCFs), lesion number, cortical destruction, and appendicular skeleton medullary cavity (ASMC) patterns, were recorded. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and Cox regression models.

Results

VCFs were significantly associated with inferior PFS (18.1 vs. 33.6 months; p = 0.013) and OS (51.5 months vs. not reached; p = 0.023) in univariate analyses. However, in multivariable models, no imaging parameter, including VCFs, retained independent prognostic significance. Other imaging variables (lesion count, ASMC subtype, cortical destruction) were not predictive of outcomes.

Conclusions

While VCFs identified on WBLDCT correlate with poor outcomes in univariate analysis, they do not serve as independent prognostic markers when adjusting for established clinical factors. These findings suggest that in the era of novel anti-myeloma therapeutics, the bone disease burden at diagnosis may not impact prognosis significantly.

背景：多发性骨髓瘤（MM）经常表现为骨髓瘤骨病（MBD），表现为溶骨病变和骨骼相关事件（SREs），显著降低生活质量，增加发病率。全身低剂量计算机断层扫描（WBLDCT）已成为诊断时评估骨受累的标准，但其预后意义尚不清楚。本研究的目的是利用WBLDCT评估新诊断MM患者的MBD负担，并检查影像学特征与生存结果之间的关系。方法回顾性、单中心分析119例MM患者，在诊断前进行WBLDCT检查。记录影像学表现，包括椎体压缩性骨折（VCFs）、病变数量、皮质破坏和阑尾骨髓腔（ASMC）模式。采用Kaplan-Meier曲线和Cox回归模型分析无进展生存期（PFS）和总生存期（OS）。结果单因素分析中，vcf与不良PFS （18.1 vs. 33.6 个月；p = 0.013）和OS（51.5 个月vs.未达到；p = 0.023）显著相关。然而，在多变量模型中，没有影像学参数（包括vcf）保留独立的预后意义。其他影像学变量（病变计数、ASMC亚型、皮质破坏）不能预测预后。结论：虽然在单因素分析中，在WBLDCT上发现的vcf与不良预后相关，但在调整已确定的临床因素时，它们不能作为独立的预后指标。这些发现表明，在新型抗骨髓瘤疗法的时代，诊断时的骨病负担可能不会显著影响预后。

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引用次数: 0

Establishment and comprehensive characterization of a subline with highly bone-metastatic propensity derived from the lung adenocarcinoma A549 cell line 从肺腺癌A549细胞系衍生的具有高度骨转移倾向的亚系的建立和综合表征

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-12-01 Epub Date: 2025-10-22 DOI: 10.1016/j.jbo.2025.100719

Yujian Xu , Yahan Qin , Wenjun Chai , Ke Xue , Xiaoli Liu , Jing Li , Yue Cao , Lei Sun , Hongyu Pan , Mingxia Yan

Bone metastasis is a major cause of mortality in lung adenocarcinoma, but the mechanisms remain poorly understood. Here, we established a highly bone-metastatic subline, A549-BM5, from the A549 cell line through five rounds of in vivo selection. A549-BM5 cells exhibited enhanced migration and invasion, and preferentially colonized specific skeletal sites in mouse models. In the bone microenvironment, they promoted the recruitment and differentiation of osteoblasts and osteoclasts, disrupting bone homeostasis. Transcriptomic and proteomic profiling revealed dysregulation in pathways such as EMT, adhesion, and bone morphogenesis. We further applied a random forest model to identify potential therapeutic targets associated with bone metastasis. Compared to existing A549-based models, A549-BM5 offers earlier metastasis onset, stable bone tropism, and broader interaction with the bone niche. This model provides a valuable platform for mechanistic studies and therapeutic development targeting lung cancer bone metastasis.

骨转移是肺腺癌死亡的主要原因，但其机制尚不清楚。在这里，我们从A549细胞系中通过五轮体内选择建立了一个高度骨转移亚系A549- bm5。在小鼠模型中，A549-BM5细胞表现出增强的迁移和侵袭，并优先定植特定的骨骼部位。在骨微环境中，它们促进成骨细胞和破骨细胞的募集和分化，破坏骨稳态。转录组学和蛋白质组学分析揭示了EMT、粘附和骨形态发生等途径的失调。我们进一步应用随机森林模型来确定与骨转移相关的潜在治疗靶点。与现有的基于a549的模型相比，A549-BM5具有更早的转移发生、稳定的骨向性以及与骨生态更广泛的相互作用。该模型为肺癌骨转移的机制研究和治疗开发提供了一个有价值的平台。

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引用次数: 0