Journal of Bone Oncology最新文献_第8页

Glutathione peroxidase 7 knockdown inhibits growth, invasion, and migration while enhancing oxidative stress and ferroptosis in osteosarcoma cells 谷胱甘肽过氧化物酶7敲低抑制骨肉瘤细胞的生长、侵袭和迁移，同时增强氧化应激和铁下垂

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-05-31 DOI: 10.1016/j.jbo.2025.100692

Runze He , Xiao Xiao , Xinwen Tang , Chen Lv

Background

Glutathione peroxidase 7 (GPX7) possesses antioxidant functions and plays a crucial role in regulating cancer progression. However, relevant evidence in osteosarcoma is scarce. The current study aimed to explore the effect of GPX7 on osteosarcoma progression, oxidative stress, and ferroptosis.

Methods

Human osteosarcoma cells (U2OS, MG-63, and SaOS-2) were transfected with GPX7 small interfering RNA (siGPX7). Proliferation, apoptosis, invasion, migration, oxidative stress markers, Fe²⁺ levels, and ferroptosis markers were detected in human osteosarcoma cells.

Results

GPX7 knockdown inhibited human osteosarcoma cell proliferation, as evidenced by reduced relative cell viability and 5-Ethynyl-2′-deoxyuridine positive cells. GPX7 knockdown also showed a certain ability to promote human osteosarcoma cell apoptosis, as evidenced by increased terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) positive rate and cleaved-caspase3. GPX7 knockdown decreased invasive and migration rates of human osteosarcoma cells. GPX7 knockdown increased reactive oxygen species and malondialdehyde but decreased mitochondrial membrane potential, suggesting that GPX7 knockdown enhanced oxidative stress in human osteosarcoma cells. Regarding ferroptosis markers, GPX7 knockdown increased acyl-CoA synthetase long-chain family member 4 and reduced solute carrier family 7 member 11; moreover, GPX7 knockdown increased Fe²⁺ levels; the above findings indicated that GPX7 knockdown promoted ferroptosis in human osteosarcoma cells.

Conclusion

GPX7 knockdown inhibits osteosarcoma cell growth, invasion, and migration while facilitating oxidative stress and ferroptosis.

谷胱甘肽过氧化物酶7 （gtathione peroxidase 7, GPX7）具有抗氧化功能，并在调节癌症进展中发挥重要作用。然而，骨肉瘤的相关证据很少。本研究旨在探讨GPX7对骨肉瘤进展、氧化应激和铁下垂的影响。方法用GPX7小干扰RNA （siGPX7）转染人骨肉瘤细胞（U2OS、MG-63、SaOS-2）。检测了人骨肉瘤细胞的增殖、凋亡、侵袭、迁移、氧化应激标志物、Fe2+水平和铁下垂标志物。结果gpx7基因敲低可抑制人骨肉瘤细胞的增殖，降低细胞的相对活力和5-乙基-2 ' -脱氧尿苷阳性细胞。GPX7敲低也显示出一定的促进人骨肉瘤细胞凋亡的能力，这可以通过增加终端脱氧核苷酸转移酶介导的nick end labeling （TUNEL）阳性率和cleaved-caspase3来证明。GPX7敲低可降低人骨肉瘤细胞的侵袭和迁移率。GPX7敲低增加了活性氧和丙二醛，但降低了线粒体膜电位，表明GPX7敲低增强了人骨肉瘤细胞的氧化应激。在铁下垂标志物方面，GPX7敲低增加了酰基辅酶a合成酶长链家族成员4，降低了溶质载体家族7成员11；GPX7敲低使Fe2+水平升高；上述结果表明，敲低GPX7可促进人骨肉瘤细胞铁下垂。结论px7基因敲低抑制骨肉瘤细胞生长、侵袭和迁移，促进氧化应激和铁下垂。

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引用次数: 0

Comparative analysis of X-ray, CT, and MRI images in patients with chondroblastoma in tubular and non-tubular bones 管状骨和非管状骨成软骨细胞瘤x线、CT和MRI影像的对比分析

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-05-28 DOI: 10.1016/j.jbo.2025.100691

Xiang Feng , Yuxiang Fang , Hanhua Yu , Zhanqiang Song , Xiangrong Guo , Man Yang

Objective

To compare and analyze the image features of X-ray, computerized tomography (CT), and magnetic resonance imaging (MRI) in patients with chondroblastoma (CB) in tubular and non-tubular bones, to improve the preoperative diagnostic accuracy and follow-up the postoperative recurrence rate.

Methods

Sixty-one CB patients confirmed by surgical pathology in our hospital and Huazhong University of Science and Technology Tongji Medical College Affiliated Union Hospital from August 2013 to March 2024 were included in this study. Their clinical, image, and pathological data were retrospectively collected and analyzed. Clinical data included age and gender. Image data included lesion size, lobulation, distensibility, bone crest, calcification, sclerotic margin, periosteal reaction, soft tissue swelling, fluid level, and aneurysmal bone cyst (ABC). Pathologic data included pathological findings and immunohistochemistry (IHC).

Results

The average onset age in tubular bone and non-tubular bone groups was 17.3 ± 5.5 and 25.6 ± 5.7 respectively (p = 0.00). The percentage of distensibility with or without was 37 %, 63 %, 69 % and 31 % (p = 0.01), the percentage of bone crest with or without was 46 %, 54 %, 77 % and 20 % (p = 0.01), and the percentage of fluid level with or without was 17 %, 83 %, 62 % and 38 % in tubular bone and non-tubular bone groups, respectively (p = 0.00). CB was predominantly non-calcified or mottled calcification in patients with lesions less than 12 months and patchy or cloudy calcification in patients with lesions more than 12 months. CB of the calcaneus and talus accounted for 54 % of the CB of the non-tubular bones. There was one case of preoperative malignant lesion and one case of postoperative recurrence.

Conclusion

Lesions in CB patients in non-tubular bone are swollen and are prone to form a coarse bone creast and fluid level, and the bone swells even more obviously when CB is combined with ABC. There is a low possibility of malignant transformation and postoperative recurrence in CB patients.

目的比较分析管状骨与非管状骨成软骨细胞瘤（CB）患者的x线、CT、MRI影像特征，提高术前诊断准确率和术后随访复发率。方法选取2013年8月至2024年3月在我院及华中科技大学同济医学院附属协和医院经手术病理证实的肺结核患者61例。回顾性收集并分析其临床、影像及病理资料。临床资料包括年龄和性别。影像资料包括病灶大小、分叶、膨胀性、骨嵴、钙化、硬化边缘、骨膜反应、软组织肿胀、液面和动脉瘤性骨囊肿（ABC）。病理资料包括病理结果和免疫组化（IHC）。结果管状骨组和非管状骨组的平均发病年龄分别为17.3±5.5岁和25.6±5.7岁（p = 0.00）。管状骨组和非管状骨组的胸廓扩张率分别为37%、63%、69%和31% (p = 0.01)，胸廓扩张率分别为46%、54%、77%和20% (p = 0.01)，液面扩张率分别为17%、83%、62%和38% （p = 0.00）。病变小于12个月的CB主要是非钙化或斑驳钙化，病变大于12个月的CB主要为斑片状或浑浊钙化。跟骨和距骨的骨量占非管状骨骨量的54%。术前恶性病变1例，术后复发1例。结论CB患者非管状骨病变肿胀，易形成粗骨嵴和液面，合并ABC时骨肿胀更为明显。CB患者恶性转化和术后复发的可能性较低。

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引用次数: 0

The metastatic role of the CXCL10-CXCR3 axis and its therapeutic potential in osteosarcoma CXCL10-CXCR3轴的转移作用及其在骨肉瘤中的治疗潜力

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-05-23 DOI: 10.1016/j.jbo.2025.100690

Benjamin B. Gyau , Junyan Wang , Xiang Chen , Margaret A. Clement , Zoe D. Man , Angela M. Major , Mathew C. Weiser , Jun Xu , John Hicks , Tsz-Kwong Man

The CXCL10-CXCR3 axis regulates immunity, tumorigenesis, and metastasis in multiple cancers. Yet, its roles in osteosarcoma (OS), the predominant pediatric malignant bone tumor, are not fully defined. Our prior work has shown that elevated serum CXCL10 levels correlate with poor OS prognosis. The current study delves deeper by investigating how CXCL10-mediated CXCR3 signaling influences OS growth and metastatic spread. In vitro, CXCL10 and related CXCR3 ligands (CXCL4, CXCL9, and CXCL11) enhanced OS tumor cell migration. In an orthotopic xenograft mouse model with a newly created CXCR3 knockout (KO) mutant, tumor growth and lung metastasis decreased significantly when compared with the parental cell line. Transfecting the transcript isoform CXCR3A, but not CXCR3B, into KO cells restored metastatic phenotypes in mice, highlighting isoform specificity. Pharmacological CXCR3 inhibition reduced OS cell migration in vitro and metastasis in vivo. Mechanistically, CXCL10 triggered AKT (S473) and PAK1 (S144) phosphorylation in OS cell lines, but not in the KO mutant, implicating the role of these kinases in CXCL10-mediated metastasis. Collectively, our data indicate the CXCL10-CXCR3 axis as a key metastatic driver in OS, suggesting CXCR3 as a viable therapeutic target for treating OS metastasis.

CXCL10-CXCR3轴调节多种癌症的免疫、肿瘤发生和转移。然而，它在主要的儿童恶性骨肿瘤骨肉瘤（OS）中的作用尚未完全确定。我们之前的研究表明血清CXCL10水平升高与不良的OS预后相关。目前的研究通过研究cxcl10介导的CXCR3信号传导如何影响OS的生长和转移扩散进行了更深入的研究。在体外，CXCL10和相关的CXCR3配体（CXCL4、CXCL9和CXCL11）增强了OS肿瘤细胞的迁移。在具有新创建的CXCR3敲除（KO）突变体的原位异种移植小鼠模型中，与亲代细胞系相比，肿瘤生长和肺转移显著降低。将转录异构体CXCR3A而不是CXCR3B转染到小鼠KO细胞中，可以恢复小鼠的转移表型，突出了异构体的特异性。药理抑制CXCR3可减少OS细胞的体外迁移和体内转移。从机制上讲，CXCL10在OS细胞系中触发了AKT （S473）和PAK1 （S144）的磷酸化，但在KO突变体中没有，这暗示了这些激酶在CXCL10介导的转移中的作用。总的来说，我们的数据表明CXCL10-CXCR3轴是OS的关键转移驱动因素，表明CXCR3是治疗OS转移的可行治疗靶点。

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引用次数: 0

Application of responsive nano-drug carriers in bone tumor chemotherapy 反应性纳米药物载体在骨肿瘤化疗中的应用

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-05-16 DOI: 10.1016/j.jbo.2025.100689

Peiyang Cai, Minjie Fan, Pengfei Zheng

Bone tumors, especially malignant ones, have high mortality and disability rates, and traditional treatment methods have limitations. Responsive nano-drug carriers achieve targeted delivery and controlled release of drugs by precisely responding to the tumor microenvironment or external stimuli, thereby improving drug efficacy and reducing toxic side effects. These carriers, including liposomes, micelles, and nano-gels, can respond to internal stimuli such as pH, redox, enzymes, and hypoxia, as well as external stimuli such as light, magnetic fields, and ultrasound. By optimizing carrier design, significant improvements in drug targeting, bioavailability, and therapeutic effects can be achieved, providing new ideas and methods for the comprehensive treatment of bone tumors.

骨肿瘤，尤其是恶性肿瘤，死亡率和致残率高，传统的治疗方法有局限性。响应性纳米药物载体通过对肿瘤微环境或外界刺激的精确响应，实现药物的靶向递送和控释，从而提高药物疗效，减少毒副作用。这些载体，包括脂质体、胶束和纳米凝胶，可以响应内部刺激，如pH、氧化还原、酶和缺氧，以及外部刺激，如光、磁场和超声波。通过优化载体设计，可以显著提高药物的靶向性、生物利用度和治疗效果，为骨肿瘤的综合治疗提供新的思路和方法。

引用次数: 0

The impact of comprehensive local therapy on treatment outcomes of non-small cell lung cancer with solitary skeletal oligometastasis 局部综合治疗对非小细胞肺癌合并孤立性骨少转移治疗结果的影响

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-05-14 DOI: 10.1016/j.jbo.2025.100688

Jia-nan Jin , Zheng-bo Song , Wen-xian Wang , Yi Li , Shi-yan Wu

Background

The oligometastatic status of non-small lung cancer (NSCLC) has been extensively studied over the years owing to its potential significance in long-term survival. Bone is one of the most commonly affected organs in oligometastatic NSCLC. The value of comprehensive local therapy (CLT) for NSCLC with solitary skeletal oligometastasis remains to be established.

Methods

Data on NSCLC cases with solitary skeletal oligometastasis were collected retrospectively between August 2008 and March 2022. Kaplan–Meier and Cox regression analyses were performed to assess clinical outcomes.

Results

Sixty-seven patients were included in the final analysis, 23 (34.3 %) of whom received CLT. Median progression-free survival (PFS) and overall survival (OS) were 9.9 and 27.1 months for the non-CLT cohort and 18.8 and 46.0 months for the CLT cohort, respectively. In multivariate analysis, CLT emerged as an independent prognostic factor associated with improved PFS (P = 0.031), but had no significant correlation with OS (P = 0.403). Among 23 patients treated with EGFR-TKIs, the CLT group had a median PFS of 46.8 months and a median OS that was not reached, while the non-CLT group had a median PFS of 15.7 months and a median OS of 30.7 months. CLT plus EGFR-TKI significantly improved PFS versus monotherapy (P = 0.023), though OS did not differ significantly (P = 0.095).

Conclusions

In NSCLC patients with solitary skeletal oligometastasis, implementation of CLT appeared to positively influence PFS. The combination of EGFR-TKI and CLT was associated with prolonged PFS compared to EGFR-TKI alone, though further validation is needed to confirm its impact on long-term survival.

近年来，非小细胞肺癌（NSCLC）的低转移状态由于其对长期生存的潜在意义而被广泛研究。骨是少转移性非小细胞肺癌最常见的受累器官之一。局部综合治疗（CLT）对孤立性骨骼少转移NSCLC的价值仍有待确定。方法回顾性收集2008年8月至2022年3月间非小细胞肺癌单发骨少转移病例资料。采用Kaplan-Meier和Cox回归分析评估临床结果。结果67例患者纳入最终分析，其中23例（34.3%）接受了CLT治疗。非CLT组的中位无进展生存期（PFS）和总生存期（OS）分别为9.9和27.1个月，CLT组的中位无进展生存期（PFS）和总生存期（OS）分别为18.8和46.0个月。在多变量分析中，CLT成为与PFS改善相关的独立预后因素（P = 0.031），但与OS无显著相关性（P = 0.403）。在接受EGFR-TKIs治疗的23例患者中，CLT组的中位PFS为46.8个月，中位OS未达到，而非CLT组的中位PFS为15.7个月，中位OS为30.7个月。与单药治疗相比，CLT联合EGFR-TKI显著改善了PFS (P = 0.023)，但OS无显著差异（P = 0.095）。结论：在非小细胞肺癌伴孤立性骨骼少转移的患者中，CLT的实施对PFS有积极影响。与单独使用EGFR-TKI相比，EGFR-TKI联合CLT与延长PFS相关，尽管需要进一步验证以确认其对长期生存的影响。

{"title":"The impact of comprehensive local therapy on treatment outcomes of non-small cell lung cancer with solitary skeletal oligometastasis","authors":"Jia-nan Jin , Zheng-bo Song , Wen-xian Wang , Yi Li , Shi-yan Wu","doi":"10.1016/j.jbo.2025.100688","DOIUrl":"10.1016/j.jbo.2025.100688","url":null,"abstract":"<div><h3>Background</h3><div>The oligometastatic status of non-small lung cancer (NSCLC) has been extensively studied over the years owing to its potential significance in long-term survival. Bone is one of the most commonly affected organs in oligometastatic NSCLC. The value of comprehensive local therapy (CLT) for NSCLC with solitary skeletal oligometastasis remains to be established.</div></div><div><h3>Methods</h3><div>Data on NSCLC cases with solitary skeletal oligometastasis were collected retrospectively between August 2008 and March 2022. Kaplan–Meier and Cox regression analyses were performed to assess clinical outcomes.</div></div><div><h3>Results</h3><div>Sixty-seven patients were included in the final analysis, 23 (34.3 %) of whom received CLT. Median progression-free survival (PFS) and overall survival (OS) were 9.9 and 27.1 months for the non-CLT cohort and 18.8 and 46.0 months for the CLT cohort, respectively. In multivariate analysis, CLT emerged as an independent prognostic factor associated with improved PFS (P = 0.031), but had no significant correlation with OS (P = 0.403). Among 23 patients treated with EGFR-TKIs, the CLT group had a median PFS of 46.8 months and a median OS that was not reached, while the non-CLT group had a median PFS of 15.7 months and a median OS of 30.7 months. CLT plus EGFR-TKI significantly improved PFS versus monotherapy (P = 0.023), though OS did not differ significantly (P = 0.095).</div></div><div><h3>Conclusions</h3><div>In NSCLC patients with solitary skeletal oligometastasis, implementation of CLT appeared to positively influence PFS. The combination of EGFR-TKI and CLT was associated with prolonged PFS compared to EGFR-TKI alone, though further validation is needed to confirm its impact on long-term survival.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"52 ","pages":"Article 100688"},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947301","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

Single Photon Emission Computed Tomography/X-ray Computed Tomography-based radiomics analysis for diagnosis of bone metastases in patients with breast cancer 基于单光子发射计算机断层扫描/ x射线计算机断层扫描的放射组学分析诊断乳腺癌患者骨转移

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-05-10 DOI: 10.1016/j.jbo.2025.100686

Huiyu Su , Chunwen Ma , Dongli Sun , Jianhua Jin

Purpose

Bones are the most metastatic site for breast cancer (BC), which can cause complications such as pathologic osteolysis, seriously affecting the quality of life of patients. This study intended to investigate the efficacy of Single Photon Emission Computed Tomography/X-ray Computed Tomography (SPECT/CT) in diagnosing bone metastases in BC and to develop a model for predicting the diagnostic effectiveness.

Methods

In this study, we enrolled 185 patients with BC who underwent SPECT/CT scanning. The region of interest (ROI) of each SPECT/CT image was demarcated, and the radiomics features were determined from the ROIs and screened for the optimal features signature to construct the radiomics model. Based on clinical characteristics, the clinical model was developed, and the independent predictive factors were discovered through univariate and multivariate COX regression analyses. Additionally, the radiomics nomogram was created through integrating the radiomics score and independent predictive factors. Thereafter, the receiver operating characteristic (ROC) was applied to determine the diagnostic performance of various models.

Results

The radiomics model was constructed based on 29 optimal features. The N stage was an independent factor, and the radiomics nomogram was created through integrating the radiomics score and N stage. Among three models, the radiomics nomogram had the highest diagnostic value for BC bone metastasis (AUC: the training set: 0.956 (0.909–1.000); the validation set: 0.936 (0.866–1.000)).

Conclusion

Radiomics analysis based on SPECT/CT can effectively diagnose bone metastasis in BC patients, establishing a theoretical foundation for the formulation of personalized treatment options in clinical practice.

目的：骨是乳腺癌（BC）最易转移的部位，可引起病理性骨溶解等并发症，严重影响患者的生活质量。本研究旨在探讨单光子发射计算机断层扫描/ x射线计算机断层扫描（SPECT/CT）诊断BC骨转移的有效性，并建立预测诊断有效性的模型。方法在本研究中，我们招募了185例接受SPECT/CT扫描的BC患者。对每幅SPECT/CT图像的感兴趣区域（ROI）进行划分，根据感兴趣区域确定放射组学特征，筛选最优特征签名，构建放射组学模型。根据临床特点建立临床模型，通过单因素和多因素COX回归分析发现独立预测因素。此外，通过整合放射组学评分和独立预测因素创建放射组学nomogram。然后，应用受试者工作特征（ROC）来确定各种模型的诊断性能。结果基于29个最优特征构建了放射组学模型。N分期为独立因素，将放射组学评分与N分期相结合，形成放射组学nomogram。三种模型中，放射组学模式图对BC骨转移的诊断价值最高(AUC：训练集：0.956 (0.909 ~ 1.000)；验证集：0.936(0.866-1.000))。结论基于SPECT/CT的放射组学分析可有效诊断BC患者骨转移，为临床制定个性化治疗方案奠定理论基础。

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引用次数: 0

Predicting lung metastasis in high-grade Osteosarcoma: The role of CTA Signs, with a Focus on vascular wrapping and intratumoral vascular network 预测高级别骨肉瘤的肺转移：CTA征象的作用，重点是血管包裹和肿瘤内血管网络

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-05-09 DOI: 10.1016/j.jbo.2025.100687

Zhendong Luo , Tao Ai , Zhiqiang Liu , Litong He , Yanzhen Hou , Yulin Li , Ziyan Zhou , Xinping Shen

Objective

Osteosarcoma is a highly malignant bone tumor with a high incidence of lung metastases (LM), significantly impacting the 5-year survival rate of patients. This study aims to predict lung metastasis in osteosarcoma based on computed tomography angiography (CTA) signs.

Methods

A retrospective study was conducted involving 89 consecutive patients with osteosarcoma. Clinical features and CTA signs, including age, gender, laterality, primary site, type of bone destruction, T stage, periosteal reaction, tumor length, bone marrow involved length, vascular wrapping, and intratumoral vascular network, were evaluated. Univariate and multivariate logistic regression analyses were used to identify risk factors for LM, followed by receiver operating characteristic (ROC) curve analysis.

Results

The vascular wrapping and intratumoral vascular network signs were more frequently observed in LM in patients with osteosarcoma (P < 0.05). The intratumoral vascular network remained an independent risk factor in multivariable regression analysis. ROC curve analysis demonstrated that the area under the curve (AUC) of the logistic regression model was 0.804, indicating good predictive accuracy.

Conclusion

Preliminary findings suggest that CTA signs, particularly vascular wrapping and the intratumoral vascular network, may have potential utility in predicting lung metastasis (LM) in osteosarcoma patients. The intratumoral vascular network, in particular, was identified as an independent risk factor.

目的骨肉瘤是一种高恶性骨肿瘤，肺转移（LM）发生率高，严重影响患者5年生存率。本研究旨在基于计算机断层血管造影（CTA）征象预测骨肉瘤的肺转移。方法对89例骨肉瘤患者进行回顾性研究。评估临床特征和CTA征象，包括年龄、性别、侧边性、原发部位、骨破坏类型、T分期、骨膜反应、肿瘤长度、骨髓受累长度、血管包裹和肿瘤内血管网络。采用单因素和多因素logistic回归分析确定LM的危险因素，然后进行受试者工作特征（ROC）曲线分析。结果骨肉瘤患者LM中血管包裹和瘤内血管网征象较多(P <；0.05)。在多变量回归分析中，肿瘤内血管网络仍然是一个独立的危险因素。ROC曲线分析表明，logistic回归模型的曲线下面积（AUC）为0.804，预测精度较好。结论CTA征象，特别是血管包裹和瘤内血管网络，可能在预测骨肉瘤患者肺转移（LM）方面具有潜在的应用价值。尤其是瘤内血管网络，被认为是一个独立的危险因素。

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引用次数: 0

Analysis of skeletal pain, general symptoms and patient-reported outcome measures and their value in detecting symptomatic progression – An interdisciplinary prospective study in patients with multiple myeloma 分析骨骼疼痛、一般症状和患者报告的结果测量及其在检测症状进展中的价值——多发性骨髓瘤患者的跨学科前瞻性研究

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-05-08 DOI: 10.1016/j.jbo.2025.100685

Carlotta Pietsch , Monika Engelhardt , Gabriele Ihorst , Laura Wystrach , Johannes Jung , Hagen Schmal , Andreas Frodl , Ralph Wäsch , Evangelos Terpos , Georg W. Herget

Delayed diagnosis of multiple myeloma (MM) and progressive disease (PD) can both increase the risk of skeletal complications and do affects patients’ quality of life (QoL). In this prospective study we analyzed skeletal pain, general symptoms and patient-reported outcome measures (PROMs) in patients with MM and their value in detecting symptomatic progression.

We evaluated 502 patients, 47 with initial diagnosis (ID) of MM and 455 follow-up patients. At ID, 74% reported bone pain, mostly in the spine. General symptoms, particularly fatigue, were present in 89% of the patients. 88/455 (19%) of the follow-up patients experienced PD. Of these, 65% reported skeletal pain and 81% exhibited general symptoms, with fatigue being the most common. PD was suspected and confirmed as the cause of clinical symptoms in 59/88 (67%) and not suspected in 29/88 (33%). Occurrence and character of bone pain and general symptoms differed significantly between patients with and without PD, as did QoL and health-related status. Logistic regression analysis demonstrated that bone pain at night, pain in various locations, pain of known character with occurrence in different location, pain in the chest, pelvis, and thigh as well as fatigue and weight loss were associated with an increased risk of PD.

In conclusion, bone pain and general symptoms are helpful in identifying both MM and PD. PROMs can aid in the diagnosis of PD through symptom-based patient assessment. Serologic and, especially in the case of skeletal complaints, additional radiologic diagnostics are required to confirm suspected and to detect unexpected PD.

多发性骨髓瘤（MM）和进行性疾病（PD）的延迟诊断既会增加骨骼并发症的风险，也会影响患者的生活质量（QoL）。在这项前瞻性研究中，我们分析了MM患者的骨骼疼痛、一般症状和患者报告的结果测量（PROMs）及其在检测症状进展中的价值。我们评估了502例患者，其中47例为初诊MM， 455例为随访患者。在ID时，74%的患者报告骨痛，主要在脊柱。一般症状，特别是疲劳，出现在89%的患者。88/455（19%）的随访患者出现PD。其中，65%报告骨骼疼痛，81%表现出一般症状，疲劳是最常见的。59/88（67%）怀疑并确认PD为临床症状的原因，29/88（33%）未怀疑PD。骨痛和一般症状的发生和特征在PD患者和非PD患者之间存在显著差异，生活质量和健康状况也存在显著差异。Logistic回归分析显示，夜间骨痛、不同部位疼痛、不同部位发生的已知特征疼痛、胸部、骨盆和大腿疼痛以及疲劳和体重减轻与PD风险增加相关。总之，骨痛和一般症状有助于鉴别MM和PD。PROMs可以通过基于症状的患者评估来帮助诊断PD。血清学和，特别是骨骼疾病的情况下，需要额外的放射学诊断来确认疑似和发现意外的PD。

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引用次数: 0

The phosphatase CTDSPL2 promotes proliferation, invasion, metastasis and regorafenib resistance in osteosarcoma 磷酸酶CTDSPL2促进骨肉瘤的增殖、侵袭、转移和瑞非尼耐药

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-04-26 DOI: 10.1016/j.jbo.2025.100684

Guannan Bai , Shaobo Zhao , Manli Zhao , Limiao Chen , Wenhao Chen

Osteosarcoma is the most common bone malignancy in children and adolescents. Patients with metastatic and recurrent osteosarcoma have poor prognosis. Regorafenib is a multi-kinase inhibitor recommended as a complement to standard chemotherapy in the treatment of advanced osteosarcoma. The mechanisms associated with regorafenib resistance remains unclear.

In this study we performed transcriptomics, proteomics and phosphorylated proteomics using regorafenib-treated osteosarcoma cell lines (MG-63, HOS-MNNG for transcriptomics, HOS-MNNG for proteomics and phosphorylated proteomics). After comprehensive multiomics and verification analyses of differentially expressed genes, essential genes for the malignancy of osteosarcoma cells were identified. The effects of essential genes on the proliferation, invasion, and migration of osteosarcoma were determined. The study also evaluated their role in the apoptosis of osteosarcoma cells. The up-regulation of essential genes was determined by immunohistochemistry assays.

Using comprehensive multiomics and verification analyses we found that the CTDSPL2 gene might play a role in the malignancy and Regorafenib resistance in osteosarcoma. In vitro and clinical specimen assays demonstrated that CTDSPL2 promotes the proliferation, invasion and metastasis of osteosarcoma cells, while inhibiting tumor cell apoptosis.

In conclusion CTDSPL2 was identified as an essential gene for survival of osteosarcoma cells. Knockdown of CTDSPL2 expression significantly inhibited the proliferation, invasion, and metastasis of osteosarcoma cells, suggesting that it is involved in the formation and development of osteosarcoma tumors. Our data showed that CTDSPL2 is a potential therapeutic target for patients with osteosarcoma.

骨肉瘤是儿童和青少年中最常见的骨恶性肿瘤。转移性和复发性骨肉瘤患者预后较差。瑞非尼是一种多激酶抑制剂，推荐作为晚期骨肉瘤治疗标准化疗的补充。与瑞非尼耐药相关的机制尚不清楚。在这项研究中，我们使用regorafenib处理的骨肉瘤细胞系（MG-63， HOS-MNNG用于转录组学，HOS-MNNG用于蛋白质组学和磷酸化蛋白质组学）进行转录组学、蛋白质组学和磷酸化蛋白质组学研究。通过对差异表达基因的综合多组学和验证分析，鉴定出骨肉瘤细胞恶性肿瘤的必要基因。研究了必需基因对骨肉瘤增殖、侵袭和迁移的影响。该研究还评估了它们在骨肉瘤细胞凋亡中的作用。通过免疫组化检测必需基因的上调。通过综合多组学和验证分析，我们发现CTDSPL2基因可能在骨肉瘤的恶性和瑞非尼耐药中发挥作用。体外和临床标本实验表明，CTDSPL2促进骨肉瘤细胞的增殖、侵袭和转移，同时抑制肿瘤细胞凋亡。综上所述，CTDSPL2是骨肉瘤细胞存活的重要基因。下调CTDSPL2表达可显著抑制骨肉瘤细胞的增殖、侵袭和转移，提示其参与骨肉瘤肿瘤的形成和发展。我们的数据显示CTDSPL2是骨肉瘤患者的潜在治疗靶点。

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引用次数: 0

Development and validation of a nomogram for prognosis of bone metastatic disease in patients with esophageal squamous cell carcinoma: A retrospective study in the SEER database and China cohort 食管鳞状细胞癌患者骨转移疾病预后nomogram的建立和验证：SEER数据库和中国队列的回顾性研究

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology

Pub Date : 2025-04-26 DOI: 10.1016/j.jbo.2025.100683

Bo Huang , Wei-Dong Wang , Fang-Cai Wu , Xiao-Mei Wang , Bu-Qing Shao , Ying-Miao Lin , Guo-Xing Zheng , Gui-Qiang Li , Can-Tong Liu , Yi-Wei Xu , Xin-Jia Wang

Purpose

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor worldwide, and individuals with ESCC and bone metastasis (BM) often face a challenging prognosis. Our objective was to identify the risk and prognostic factors associated with BM in patients with ESCC and develop a nomogram for predicting Cancer-Specific Survival (CSS) which following the occurrence of BM.

Methods

We conducted a retrospective analysis of data pertaining to ESCC patients with BM registered in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015, as well as those treated at a Chinese institution from 2006 to 2020. Significant prognostic factors for CSS were assessed through univariate and multivariate Cox regression analyses. Subsequently, a nomogram was developed utilizing the SEER database and externally validated using real-world evidence from a Chinese cohort.

Results

A total of 266 patients from the SEER database and 168 patients from the Chinese cohort were included in the analysis. In the SEER cohort, multivariate analysis indicated that chemotherapy, radiotherapy, liver metastasis, brain metastasis, and sex were independent prognostic factors for ESCC with BM. The prognostic nomogram demonstrated areas under the ROC curve (AUCs) of 0.823, 0.796, and 0.800, respectively, for predicting 3-, 6-, and 12-month CSS. In the Chinese validation cohort, the nomogram exhibited acceptable discrimination (AUCs: 0.822, 0.763, and 0.727) and calibration ability.

Conclusion

The study developed a prognostic nomogram to predict CSS in ESCC patients with BM, which can help clinicians assess survival and make individualized treatment decisions.

目的食管鳞状细胞癌（ESCC）是一种世界范围内常见的恶性肿瘤，ESCC合并骨转移（BM）患者的预后往往具有挑战性。我们的目的是确定ESCC患者与脑转移相关的风险和预后因素，并制定预测脑转移发生后癌症特异性生存（CSS）的nomogram。方法：我们对2010年至2015年在监测、流行病学和最终结果（SEER）数据库中登记的ESCC BM患者以及2006年至2020年在中国一家机构治疗的患者进行了回顾性分析。通过单因素和多因素Cox回归分析评估CSS的重要预后因素。随后，利用SEER数据库开发了一个nomogram，并使用来自中国队列的真实世界证据进行了外部验证。结果来自SEER数据库的266例患者和来自中国队列的168例患者被纳入分析。在SEER队列中，多因素分析显示化疗、放疗、肝转移、脑转移和性别是ESCC合并BM的独立预后因素。预测3个月、6个月和12个月CSS的ROC曲线下面积（auc）分别为0.823、0.796和0.800。在中国验证队列中，nomogram具有可接受的辨别能力（auc分别为0.822、0.763和0.727）和校正能力。结论本研究建立了一种预测ESCC合并BM患者CSS的预后nomogram，可以帮助临床医生评估生存期并制定个性化的治疗决策。

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