1.Astragali Radix-Curcumae Rhizoma drug pair inhibits growth of osteosarcoma by affecting cell adhesion and angiogenesis via PI3K/Akt/HIF-1α pathway.
Dao-Tong YUAN ; Zhi-Meng ZHANG ; Rui GONG ; Xi-Min JIN ; Can-Ran WANG ; Jie ZHAO
China Journal of Chinese Materia Medica 2025;50(8):2217-2228
This study aims to investigate the optimal ratio of Astragali Radix-Curcumae Rhizoma(AC) for inhibiting the proliferation of 143B osteosarcoma cells, and to investigate the mechanism by which AC inhibits osteosarcoma growth and metastasis through angiogenesis and cell adhesion mediated by the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor-1α(HIF-1α) pathway. A subcutaneous 143B tumor-bearing nude mouse model was successfully established and randomly divided into the model group, and the AC 1∶1, 2∶1, and 4∶1 groups. Body weight, tumor volume, and tumor weight were recorded. Real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of PI3K, Akt, phosphorylated Akt(p-Akt), HIF-1α, vascular endothelial growth factor A(VEGFA), transforming growth factor-β1(TGF-β1), epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, matrix metalloproteinase 2(MMP2), matrix metalloproteinase 9(MMP9), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3 in the hypoxic core region of the tumor tissue. A cell hypoxia model was established, and the effects of AC-medicated serum(model group, AC 1∶1, 2∶1, and 4∶1 groups) on angiogenesis, proliferation, adhesion, invasion, and migration of 143B osteosarcoma cells were examined through CCK-8, flow cytometry, Transwell assay, cell adhesion assay, and HUVEC tube formation assay. The results showed that compared with the model group, the tumor weight and volume were smallest in the 2∶1 group. The expression levels of PI3K, Akt, p-Akt, HIF-1α, VEGFA, and TGF-β1 were significantly decreased, and the protein expression of E-cadherin was significantly increased, while the protein expression of N-cadherin, vimentin, MMP2, and MMP9 was significantly decreased. Additionally, the protein expression of Bax and caspase-3 was significantly increased, and Bcl-2 protein expression was significantly decreased. In vitro experiments showed that after intervention with AC-medicated serum at a 2∶1 ratio, the cell activity, adhesion, invasion, and migration of 143B cells were significantly reduced, apoptosis was significantly increased, and HUVEC tube formation was significantly decreased. In conclusion, the 2∶1 ratio of AC showed the most effective inhibition of 143B cell growth. AC can inhibit the growth and metastasis of osteosarcoma 143B cells by regulating the PI3K/Akt/HIF-1α signaling pathway, inhibiting angiogenesis and reducing cell adhesion, invasion, and migration.
Osteosarcoma/pathology*
;
Animals
;
Proto-Oncogene Proteins c-akt/genetics*
;
Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
;
Humans
;
Mice
;
Cell Adhesion/drug effects*
;
Cell Proliferation/drug effects*
;
Neovascularization, Pathologic/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
;
Phosphatidylinositol 3-Kinases/genetics*
;
Cell Line, Tumor
;
Mice, Nude
;
Signal Transduction/drug effects*
;
Astragalus Plant/chemistry*
;
Bone Neoplasms/physiopathology*
;
Male
;
Rhizome/chemistry*
;
Mice, Inbred BALB C
;
Angiogenesis
2.Interpretation of important issues of the secondary clinical practice guideline on management of primary malignant bone tumors by the Japanese Orthopaedic Association.
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(7):814-823
Primary malignant bone tumors are extremely rare. Osteosarcoma, chondrosarcoma, Ewing's sarcoma, and myeloma are the most common malignancy in bone. Osteosarcoma and Ewing's sarcoma are common in children and adolescents, and the tumors are high lethality due to the high rate of pulmonary metastasis. While chondrosarcoma, myeloma, and chordoma are more common in middle aged and elderly people. Japanese Orthopaedic Association (JOA) published the secondary clinical practice guideline on the management of primary malignant bone tumors. We put an emphasis on explanation some important issue of this guideline for help Chinese musculoskeletal tumor professionals in clinical practice.
Humans
;
Bone Neoplasms/surgery*
;
Chondrosarcoma/therapy*
;
Japan
;
Orthopedics
;
Osteosarcoma/pathology*
;
Practice Guidelines as Topic
;
Sarcoma, Ewing/therapy*
;
Societies, Medical
3.From 2D to 3D: transforming malignant bone tumor research with advanced culture models.
Zhengcheng HE ; Haitao HUANG ; Jiale FANG ; Huiping LIU ; Xudong YAO ; Hongwei WU
Journal of Zhejiang University. Science. B 2025;26(11):1059-1075
Osteosarcoma (OS), chondrosarcoma (CS), and Ewing sarcoma (ES) represent primary malignant bone tumors and pose significant challenges in oncology research and clinical management. Conventional research methods, such as two-dimensional (2D) cultured tumor cells and animal models, have limitations in recapitulating the complex tumor microenvironment (TME) and often fail to translate into effective clinical treatments. The advancement of three-dimensional (3D) culture technology has revolutionized the field by enabling the development of in vitro constructed bone tumor models that closely mimic the in vivo TME. These models provide powerful tools for investigating tumor biology, assessing therapeutic responses, and advancing personalized medicine. This comprehensive review summarizes the recent advancements in research on 3D tumor models constructed in vitro for OS, CS, and ES. We discuss the various techniques employed in model construction, their applications, and the challenges and future directions in this field. The integration of advanced technologies and the incorporation of additional cell types hold promise for the development of more sophisticated and physiologically relevant models. As research in this field continues to evolve, we anticipate that these models will play an increasingly crucial role in unraveling the complexities of malignant bone tumors and accelerating the development of novel therapeutic strategies.
Bone Neoplasms/pathology*
;
Humans
;
Osteosarcoma/pathology*
;
Tumor Microenvironment
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Sarcoma, Ewing/pathology*
;
Chondrosarcoma/pathology*
;
Animals
;
Cell Culture Techniques/methods*
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Cell Culture Techniques, Three Dimensional/methods*
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Cell Line, Tumor
4.Expert consensus on whole-course management of prostate cancer (2025 edition).
Chinese Journal of Oncology 2025;47(7):617-634
Prostate cancer represents a prevalent malignancy within the male genitourinary system. In recent years, its incidence in China has gradually increased, becoming a significant public health issue. While early detection correlates strongly with improved prognosis, the majority of newly diagnosed prostate cancer patients in China are already in intermediate or advanced stages, precluding curative-intent interventions and contributing to marked survival disparities. The progression of prostate cancer is lengthy, typically encompassing diagnosis, treatment, progression, metastasis, and death, accompanied by a decline in quality of life. Personalized treatment plans should be developed based on the disease stage and patient preferences. In non-metastatic prostate cancer, where the tumor is confined to the prostate, surgery and radiotherapy are the primary treatments, supplemented by neoadjuvant and adjuvant therapies to delay metastasis. For metastatic prostate cancer, systemic therapy is prioritized to prolong survival. In metastatic hormone-sensitive prostate cancer, controlling androgen levels is crucial, while treatment options for metastatic castration resistant prostate cancer are relatively limited, necessitating individualized and precise treatment. During prostate cancer management, prostate-specific antigen levels are closely linked to prognosis and require monitoring. Bone metastasis, the most common site in prostate cancer patients, often triggers skeletal-related events, demanding effective prevention and management. Treatment-related adverse reactions are also a clinical challenge, requiring balanced risk-benefit assessments and judicious drug selection to preserve quality of life. Rapid advancements in screening technologies, surgical innovations, drug development, and China-specific epidemiological factors further complicate decision-making in holistic prostate cancer management. To optimize the standardization of prostate cancer diagnosis and treatment in China, the Genitourinary Oncology Committee of Chinese Anti-cancer Association synthesized global guidelines, clinical evidence and clinical expertise, and addressed critical challenges in the whole-course management of prostate cancer to formulate a multidisciplinary consensus. The expert consensus on whole-course management of prostate cancer (2025 edition) establishes standardized protocols to guide clinical practice, improve treatment outcomes, and enhance patient quality of life.
Humans
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Male
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Prostatic Neoplasms/diagnosis*
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Consensus
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Prostate-Specific Antigen/blood*
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Quality of Life
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Prostatic Neoplasms, Castration-Resistant/pathology*
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China
;
Bone Neoplasms/secondary*
;
Androgen Antagonists/therapeutic use*
5.Prognostic value and mechanism of long non-coding RNA DLEU1 in osteosarcoma.
Jing-Jing ZHANG ; Ping YANG ; Xiao-Qiang SHANG
China Journal of Orthopaedics and Traumatology 2023;36(6):559-564
OBJECTIVE:
To investigate the prognostic value and mechanism of long non-coding RNA DLEU1(LncRNA DLEU1) in osteosarcoma.
METHODS:
The tissue samples and clinical data of 86 patients with osteosarcoma treated by orthopaedic surgery in our hospital from January 2012 to December 2014 were retrospectively collected. The expression of LncRNA DLEU1 in pathological tissues was detected by qRT-PCR, then the patients were divided into high and low expression of LncRNA DLEU1 groups. Osteosarcoma cell line HOS was divided into two groups, down-regulated expression group (si-DLEU1 group) and negative control group (si-NC group). LncRNA DLEU1 siRNA and negative control sequence were transfected by Lipofectamine 3000. Chi-square test was used to analyze the relationship between the expression of LncRNA DLEU1 and the clinicopathological factors of osteosarcoma. Kaplan-Meier method was used to compare the difference of the overall survival rate of osteosarcoma patients between the high and low expression groups of LncRNA DLEU1. The risk factors affecting the overall survival rate of osteosarcoma were analyzed by single factor and multifactor analysis. The number of invasive cells in the two groups was determined and compared by Transwell assay.
RESULTS:
The expression of LncRNA DLEU1 in osteosarcoma tissue was higher than that in adjacent tissues (P<0.001). The expression of LncRNA DLEU1 in human osteosarcoma cell lines (MG-63, U-2 OS, and HOS) was significantly higher than that in human osteoblast line hFOB 1.19 (P<0.001). The expression of LncRNA DLEU1 was significantly correlated with Enneking stage (P<0.001), distant metastasis (P=0.016), and histological grade (P=0.028). The 1-year overall survival rate of the LncRNA DLEU1 high expression group was significantly higher than that of the low expression group (90.7% vs 60.5%, P<0.001). The 5-year overall survival rate of the LncRNA DLEU1 high expression group was significantly higher than that of the low expression group (32.6% vs 11.6%, P<0.001). Univariate analysis showed that Enneking stage (P<0.001), tumor size (P=0.043), distant metastasis (P<0.001), histological grade (P<0.001), and expression of LncRNA DLEU1 (P<0.001) were risk factors for overall survival of osteosarcoma patients. Multivariate analysis showed that high expression of LncRNA DLEU1 [HR=1.948, 95% CI(1.141, 3.641), P=0.012] and distant metastasis[HR=4.108, 95% CI(2.169, 7.780), P<0.001] were independent risk factors for overall survival of osteosarcoma patients. The number of invasive cells in si-DLEU1 group was significantly lesser than that in si-NC group(139±13 vs 357±31, P<0.001).
CONCLUSION
High expression of LncRNA DLEU1 is a molecular marker affecting the prognosis of osteosarcoma patients. Downregulation of LncRNA DLEU1 can inhibit the invasion of osteosarcoma cells.
Humans
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Prognosis
;
RNA, Long Noncoding/metabolism*
;
Retrospective Studies
;
Cell Proliferation/genetics*
;
Cell Line, Tumor
;
Osteosarcoma/genetics*
;
Bone Neoplasms/pathology*
6.Effectiveness of autologous hematopoietic stem cell transplantation in the treatment of high-risk neuroblastoma in children: a single-center clinical study.
Li-Hui WANG ; Kai CHEN ; Na ZHANG ; Jing-Wei YANG ; Ting ZHANG ; Jing-Bo SHAO
Chinese Journal of Contemporary Pediatrics 2023;25(5):476-482
OBJECTIVES:
To investigate the effectiveness of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) in the treatment of children with high-risk neuroblastoma (NB).
METHODS:
A retrospective analysis was performed on 29 children with high-risk NB who were admitted to Shanghai Children's Hospital and were treated with high-dose chemotherapy combined with ASCT from January 2013 to December 2021, and their clinical features and prognosis were analyzed.
RESULTS:
Among the 29 children treated by high-dose chemotherapy combined with ASCT, there were 18 boys (62%) and 11 girls (38%), with a median age of onset of 36 (27, 59) months. According to the International Neuroblastoma Staging System, 6 children (21%) had stage III NB and 23 children (79%) had stage IV NB, and the common metastatic sites at initial diagnosis were bone in 22 children (76%), bone marrow in 21 children (72%), and intracalvarium in 4 children (14%). All 29 children achieved reconstruction of hematopoietic function after ASCT. After being followed up for a median time of 25 (17, 45) months, 21 children (72%) had continuous complete remission and 8 (28%) experienced recurrence. The 3-year overall survival rate and event-free survival rate were 68.9%±16.1% and 61.4%±14.4%, respectively. Presence of bone marrow metastasis, neuron-specific enolase ≥370 ng/mL and positive bone marrow immunophenotyping might reduce the 3-year event-free survival rate (P<0.05).
CONCLUSIONS
Children with high-risk NB who have bone marrow metastasis at initial diagnosis tend to have a poor prognosis. ASCT combined with high-dose chemotherapy can effectively improve the prognosis of children with NB with a favorable safety profile.
Child, Preschool
;
Female
;
Humans
;
Male
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Bone Marrow Neoplasms/drug therapy*
;
China
;
Combined Modality Therapy
;
Disease-Free Survival
;
Hematopoietic Stem Cell Transplantation
;
Neuroblastoma/pathology*
;
Prognosis
;
Retrospective Studies
;
Stem Cell Transplantation
;
Transplantation, Autologous
7.Role of let-7 family in the invasion and metastasis of osteosarcoma.
Tong XIAO ; Xuan YANG ; Nanshan ZHONG ; Zhiwen LUO ; Jiaming LIU
Chinese Medical Journal 2023;136(1):120-122
10.Clinical Characteristics and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm.
Xiao-Li ZHANG ; Bing LIU ; Nan LI ; Lu-Ke LI ; Xuan-Jing JI ; Xue-Fang ZHOU ; Min-Fang WANG ; Hui-Li XU
Journal of Experimental Hematology 2023;31(1):254-260
OBJECTIVE:
To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN).
METHODS:
The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively.
RESULTS:
4 patients had bone marrow, spleen and lymph nodes involvement, 2 patients had skin lesions, and 3 patients had central nervous system infiltration. Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients, and CD304 in 3 patients. One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again. One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine.
CONCLUSION
The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.
Humans
;
Dendritic Cells
;
Retrospective Studies
;
Skin Neoplasms/pathology*
;
Antineoplastic Agents/therapeutic use*
;
Bone Marrow/pathology*
;
Myeloproliferative Disorders
;
Hematologic Neoplasms/drug therapy*

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