Methyltransferase-like 3 (METTL3) plays a crucial role in cancer progression, both in m6A modification-dependent and −independent pathways. We aimed to elucidate the mechanism by which METTL3 and the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) contribute to the pathogenesis of multiple myeloma (MM).
Methods
Bone marrow samples were collected from 56 patients with MM and 42 healthy donors, followed by assessment of METTL3 and MALAT1 levels. An interaction between METTL3 and MALAT1 was also identified. METTL3- and MALAT1-related oligonucleotides were transfected into RPMI8226 and U266 cells to explore their role in cell growth. Apoptosis, migration, proliferation, and invasion of RPMI8226 and U266 cells were assayed.
Results
Elevated METTL3 and MALAT1 levels were observed in patients with MM. Interference with METTL3 or MALAT1 inhibited the malignant behavior of RPMI8226 and U266 cells. There was an interaction between METTL3 and MALAT1. Overexpression of MALAT1 reversed the inhibitory effects of METTL3 interference on tumor cell malignancy.
Conclusion
METTL3 augments MM development by enhancing MALAT1 expression.
{"title":"Regulatory role of the METTL3/MALAT1 axis in multiple myeloma progression","authors":"Xiaohong Lu, Yafei Li, Ruie Li, Jingheng Zhang, Jiayu Peng, Yan Zhang","doi":"10.1016/j.jbo.2025.100695","DOIUrl":"10.1016/j.jbo.2025.100695","url":null,"abstract":"<div><h3>Objective</h3><div>Methyltransferase-like 3 (METTL3) plays a crucial role in cancer progression, both in m6A modification-dependent and −independent pathways. We aimed to elucidate the mechanism by which METTL3 and the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) contribute to the pathogenesis of multiple myeloma (MM).</div></div><div><h3>Methods</h3><div>Bone marrow samples were collected from 56 patients with MM and 42 healthy donors, followed by assessment of METTL3 and MALAT1 levels. An interaction between METTL3 and MALAT1 was also identified. METTL3- and MALAT1-related oligonucleotides were transfected into RPMI8226 and U266 cells to explore their role in cell growth. Apoptosis, migration, proliferation, and invasion of RPMI8226 and U266 cells were assayed.</div></div><div><h3>Results</h3><div>Elevated METTL3 and MALAT1 levels were observed in patients with MM. Interference with METTL3 or MALAT1 inhibited the malignant behavior of RPMI8226 and U266 cells. There was an interaction between METTL3 and MALAT1. Overexpression of MALAT1 reversed the inhibitory effects of METTL3 interference on tumor cell malignancy.</div></div><div><h3>Conclusion</h3><div>METTL3 augments MM development by enhancing MALAT1 expression.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100695"},"PeriodicalIF":3.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471504","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}
Pub Date : 2025-06-11DOI: 10.1016/j.jbo.2025.100694
Peyman Hadji , Matty Aapro , Nasser Al-Dagri , Majed Alokail , Emmanuel Biver , Jean-Jacques Body , Maria Luisa Brandi , Janet Brown , Cyrille Confavreux , Bernard Cortet , Matthew Drake , Peter Ebeling , Erik Fink Eriksen , Ghada El-Hajj Fuleihan , Theresa A. Guise , Nick C. Harvey , Andreas Kurth , Bente Langdahl , Willem Lems , Radmila Matijevic , Robert Coleman
Background
Women with hormone-responsive breast cancer who receive adjuvant endocrine treatment with aromatase inhibitors (AI) are known to be at higher fracture risk due to a marked increase in bone resorption. In 2017, several interdisciplinary cancer and bone societies involved in the management of women with AI-associated bone loss (AIBL) published a joint position statement comprising evidence-based recommendations and a practical management algorithm for the assessment of fracture risk and optimal treatment of this patient population.
Patients and methods
In order to provide updated recommendations that reflect recent advances in the assessment and management of AIBL since publication of the 2017 joint position statement, a systematic literature review was undertaken to identify relevant studies for analysis, including systematic reviews and meta-analyses. Individual trials identified were assessed for their level of evidence based on design, size, follow-up, and evaluation of safety, as well as the impact of bone directed treatments on breast cancer outcomes.
Results
New evidence was combined with the existing recommendations to provide an updated joint position statement regarding fracture risk assessment and implementation of bone-directed therapy.
Conclusion
Current published literature, including recent clinical trial reports, systematic reviews and meta-analyses, continue to affirm the high risk of fractures in women with breast cancer who are receiving adjuvant AI treatment, a risk which has been observed to increase with the commonly used approach of extended duration AI therapy (>5 years). Risk factors for fracture and risk assessment in this patient population as well as the most suitable treatment modalities have been updated. Finally, the influence of bone protective treatments on breast cancer outcomes such as incidence of bone metastasis and breast cancer related overall survival have been included.
{"title":"Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer: An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG","authors":"Peyman Hadji , Matty Aapro , Nasser Al-Dagri , Majed Alokail , Emmanuel Biver , Jean-Jacques Body , Maria Luisa Brandi , Janet Brown , Cyrille Confavreux , Bernard Cortet , Matthew Drake , Peter Ebeling , Erik Fink Eriksen , Ghada El-Hajj Fuleihan , Theresa A. Guise , Nick C. Harvey , Andreas Kurth , Bente Langdahl , Willem Lems , Radmila Matijevic , Robert Coleman","doi":"10.1016/j.jbo.2025.100694","DOIUrl":"10.1016/j.jbo.2025.100694","url":null,"abstract":"<div><h3>Background</h3><div>Women with hormone-responsive breast cancer who receive adjuvant endocrine treatment with aromatase inhibitors (AI) are known to be at higher fracture risk due to a marked increase in bone resorption. In 2017, several interdisciplinary cancer and bone societies involved in the management of women with AI-associated bone loss (AIBL) published a joint position statement comprising evidence-based recommendations and a practical management algorithm for the assessment of fracture risk and optimal treatment of this patient population.</div></div><div><h3>Patients and methods</h3><div>In order to provide updated recommendations that reflect recent advances in the assessment and management of AIBL since publication of the 2017 joint position statement, a systematic literature review was undertaken to identify relevant studies for analysis, including systematic reviews and meta-analyses. Individual trials identified were assessed for their level of evidence based on design, size, follow-up, and evaluation of safety, as well as the impact of bone directed treatments on breast cancer outcomes.</div></div><div><h3>Results</h3><div>New evidence was combined with the existing recommendations to provide an updated joint position statement regarding fracture risk assessment and implementation of bone-directed therapy.</div></div><div><h3>Conclusion</h3><div>Current published literature, including recent clinical trial reports, systematic reviews and meta-analyses, continue to affirm the high risk of fractures in women with breast cancer who are receiving adjuvant AI treatment, a risk which has been observed to increase with the commonly used approach of extended duration AI therapy (>5 years). Risk factors for fracture and risk assessment in this patient population as well as the most suitable treatment modalities have been updated. Finally, the influence of bone protective treatments on breast cancer outcomes such as incidence of bone metastasis and breast cancer related overall survival have been included.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100694"},"PeriodicalIF":3.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662193","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}
Pub Date : 2025-06-07DOI: 10.1016/j.jbo.2025.100693
Eskelinen Veera , Niemi Pauli , Partanen Anu , Kangas Jaakko , E.L.Kuusisto Milla
Limited data exists on the effect of treatment delay of multiple myeloma (MM) bone disease on the disease course. In this real-world analysis of 625 patients with newly diagnosed MM (NDMM) we aimed to investigate the impact of delay in starting bone disease treatment on later skeletal events and outcome.
Altogether 480 (76.8 %) patients had bone disease at the diagnosis, 282 (45.1 %) patients had a fracture at diagnosis, and 181 (29.1 %) patients had a later fracture during the follow-up. A delay in the initiation of treatment of bone disease was experienced by 221 (35.4 %) patients and tooth extraction was a main reason for the delay. Patients with a delay seemed to experience earlier and more frequent later fractures. Also, a fracture (p = 0.003) or bone disease (p < 0.001) at diagnosis predicted earlier incidence of later fractures. As a bone targeted treatment, altogether 363 (58.1 %) patients received zoledronic acid, 81 (13.0 %) denosumab and 134 (21.4 %) other bone-targeted treatment. Patients treated with denosumab had poorer overall survival (OS) (p < 0.001) and experienced earlier later fractures (p = 0.003). Multivariate analysis showed that bone disease at diagnosis (p = 0.043) and given bone disease treatment (p = 0.023) significantly impacted on the time to next fracture. Regarding OS, delay in osteoprotective treatment (p = 0.004) and time of the diagnosis (p < 0.001) were significant factors in multivariate analysis.
To conclude, this study suggests that early initiation of bone disease treatment seemed to prevent later fractures. These findings highlight the importance of patients’ rapid access to a dentist and the start of bone targeted treatment without delay after a myeloma diagnosis.
{"title":"Impact of treatment delay of multiple myeloma bone disease on later myeloma-related skeletal events and outcome","authors":"Eskelinen Veera , Niemi Pauli , Partanen Anu , Kangas Jaakko , E.L.Kuusisto Milla","doi":"10.1016/j.jbo.2025.100693","DOIUrl":"10.1016/j.jbo.2025.100693","url":null,"abstract":"<div><div>Limited data exists on the effect of treatment delay of multiple myeloma (MM) bone disease on the disease course. In this real-world analysis of 625 patients with newly diagnosed MM (NDMM) we aimed to investigate the impact of delay in starting bone disease treatment on later skeletal events and outcome.</div><div>Altogether 480 (76.8 %) patients had bone disease at the diagnosis, 282 (45.1 %) patients had a fracture at diagnosis, and 181 (29.1 %) patients had a later fracture during the follow-up. A delay in the initiation of treatment of bone disease was experienced by 221 (35.4 %) patients and tooth extraction was a main reason for the delay. Patients with a delay seemed to experience earlier and more frequent later fractures. Also, a fracture (p = 0.003) or bone disease (p < 0.001) at diagnosis predicted earlier incidence of later fractures. As a bone targeted treatment, altogether 363 (58.1 %) patients received zoledronic acid, 81 (13.0 %) denosumab and 134 (21.4 %) other bone-targeted treatment. Patients treated with denosumab had poorer overall survival (OS) (p < 0.001) and experienced earlier later fractures (p = 0.003). Multivariate analysis showed that bone disease at diagnosis (p = 0.043) and given bone disease treatment (p = 0.023) significantly impacted on the time to next fracture. Regarding OS, delay in osteoprotective treatment (p = 0.004) and time of the diagnosis (p < 0.001) were significant factors in multivariate analysis.</div><div>To conclude, this study suggests that early initiation of bone disease treatment seemed to prevent later fractures. These findings highlight the importance of patients’ rapid access to a dentist and the start of bone targeted treatment without delay after a myeloma diagnosis.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100693"},"PeriodicalIF":3.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241901","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}
Pub Date : 2025-05-31DOI: 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.
{"title":"Glutathione peroxidase 7 knockdown inhibits growth, invasion, and migration while enhancing oxidative stress and ferroptosis in osteosarcoma cells","authors":"Runze He , Xiao Xiao , Xinwen Tang , Chen Lv","doi":"10.1016/j.jbo.2025.100692","DOIUrl":"10.1016/j.jbo.2025.100692","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>Human osteosarcoma cells (U2OS, MG-63, and SaOS-2) were transfected with GPX7 small interfering RNA (siGPX7). Proliferation, apoptosis, invasion, migration, oxidative stress markers, Fe<sup>2+</sup> levels, and ferroptosis markers were detected in human osteosarcoma cells.</div></div><div><h3>Results</h3><div>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 Fe<sup>2+</sup> levels; the above findings indicated that GPX7 knockdown promoted ferroptosis in human osteosarcoma cells.</div></div><div><h3>Conclusion</h3><div>GPX7 knockdown inhibits osteosarcoma cell growth, invasion, and migration while facilitating oxidative stress and ferroptosis.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100692"},"PeriodicalIF":3.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480639","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}
Pub Date : 2025-05-28DOI: 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.
{"title":"Comparative analysis of X-ray, CT, and MRI images in patients with chondroblastoma in tubular and non-tubular bones","authors":"Xiang Feng , Yuxiang Fang , Hanhua Yu , Zhanqiang Song , Xiangrong Guo , Man Yang","doi":"10.1016/j.jbo.2025.100691","DOIUrl":"10.1016/j.jbo.2025.100691","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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).</div><div>Results</div><div>The average onset age in tubular bone and non-tubular bone groups was 17.3 ± 5.5 and 25.6 ± 5.7 respectively (<em>p</em> = 0.00). The percentage of distensibility with or without was 37 %, 63 %, 69 % and 31 % (<em>p</em> = 0.01), the percentage of bone crest with or without was 46 %, 54 %, 77 % and 20 % (<em>p</em> = 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 (<em>p</em> = 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"52 ","pages":"Article 100691"},"PeriodicalIF":3.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168091","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}
Pub Date : 2025-05-23DOI: 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.
{"title":"The metastatic role of the CXCL10-CXCR3 axis and its therapeutic potential in osteosarcoma","authors":"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","doi":"10.1016/j.jbo.2025.100690","DOIUrl":"10.1016/j.jbo.2025.100690","url":null,"abstract":"<div><div>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. <em>In vitro</em>, 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 <em>in vitro</em> and metastasis <em>in vivo</em>. 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.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"52 ","pages":"Article 100690"},"PeriodicalIF":3.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147944","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}
Pub Date : 2025-05-16DOI: 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.
{"title":"Application of responsive nano-drug carriers in bone tumor chemotherapy","authors":"Peiyang Cai, Minjie Fan, Pengfei Zheng","doi":"10.1016/j.jbo.2025.100689","DOIUrl":"10.1016/j.jbo.2025.100689","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"52 ","pages":"Article 100689"},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116310","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}
Pub Date : 2025-05-14DOI: 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.
{"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}
Pub Date : 2025-05-10DOI: 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.
{"title":"Single Photon Emission Computed Tomography/X-ray Computed Tomography-based radiomics analysis for diagnosis of bone metastases in patients with breast cancer","authors":"Huiyu Su , Chunwen Ma , Dongli Sun , Jianhua Jin","doi":"10.1016/j.jbo.2025.100686","DOIUrl":"10.1016/j.jbo.2025.100686","url":null,"abstract":"<div><h3>Purpose</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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)).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"52 ","pages":"Article 100686"},"PeriodicalIF":3.4,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943662","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}
Pub Date : 2025-05-09DOI: 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.
{"title":"Predicting lung metastasis in high-grade Osteosarcoma: The role of CTA Signs, with a Focus on vascular wrapping and intratumoral vascular network","authors":"Zhendong Luo , Tao Ai , Zhiqiang Liu , Litong He , Yanzhen Hou , Yulin Li , Ziyan Zhou , Xinping Shen","doi":"10.1016/j.jbo.2025.100687","DOIUrl":"10.1016/j.jbo.2025.100687","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>The vascular wrapping and intratumoral vascular network signs were more frequently observed in LM in patients with osteosarcoma (<em>P</em> < 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"52 ","pages":"Article 100687"},"PeriodicalIF":3.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931395","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}
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