Discover Oncology
·
2025
·Vol. 16
·期 1
·1-13
·
IF 2.9
Liu Guo,Fang Yu,Li Jiamiao,Chen Zhaofei
Osteosarcoma, the most common primary bone malignancy, poses significant management challenges due to its aggressiveness and metastatic potential. This study investigates the role of anoikis-related genes, particularly phospholipase C beta 4 (PLCB4), as a prognostic biomarker in osteosarcoma. We analyzed transcriptome data from the TARGET and GSE21257 cohorts using bioinformatics tools, identifying 15 significant genes, with PLCB4 as a key marker linked to decreased survival. Our findings indicate a negative correlation between PLCB4 and immune microenvironment scores and checkpoint molecules, suggesting its impact on immunotherapy responses. Drug sensitivity analyses revealed that high PLCB4 expression correlates with lower IC50 values for several chemotherapeutic agents. In vitro experiments showed that silencing PLCB4 inhibited cell proliferation and reduced PD-L1 expression. This study underscores the critical role of PLCB4 in osteosarcoma progression and its potential as a therapeutic target, offering insights into the molecular mechanisms of osteosarcoma biology and improving prognostic accuracy and treatment strategies.
研究领域:
肿瘤学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
·
2023
·
IF 5.1
Ziyuan Tong,Yuan Shen,Quan Yuan,Honghao Yu
Despite recent advances in understanding the biological behavior of osteosarcoma (OS), OS is still the most common primary bone sarcoma that endangers the health of children and adolescents. High-temperature requirement A (HTRA) protease family plays an important regulatory role in numerous malignancies and acts as a prognostic biomarker. However, the function and underlying mechanisms of the HTRA family in OS development remain unknown. Through analyzing the GSE126209 dataset obtained from different Gene Expression Omnibus (GEO) databases, we found that HTRA3 as a member of the HTRA family was downregulated in OS tissues compared with that in normal tissues. Functional experiments indicated that HTRA3 overexpression suppressed malignant behaviors of OS cells in vitro and tumor growth in vivo . Mechanistically, we found that HTRA3 co-localized with the X-linked inhibitor of apoptosis protein (XIAP) and decreased XIAP stability. Further investigation showed that XIAP knockdown inhibited the degradation of phosphatase and tensin homolog (PTEN) and that HTRA3 caused the blockage of PTEN/phosphoinositide 3-kinase (PI3K)/AKT pathway, characterized as the reverse of cell function caused by HTRA3 overexpression after PTEN inhibitor BpV (HOpic) treatment. Detailed investigations showed that forkhead box protein 1 (FOXP1), an oncogene in OS progression, downregulated HTRA3 expression and inhibited the transcriptional activity of HTRA3 , suggesting that HTRA3 was regulated negatively by FOXP1. In conclusion, our study demonstrates that HTRA3 is a repressor involved in OS development via the PTEN/PI3K/AKT pathway under the modulation of transcription factor FOXP1, and it may provide a therapeutic direction for OS patients.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-19
·
IF 10.2
Xu Yanlong,Du Longhai,Han Binxu,Wang Yu,Fei Jichang,Xia Kuo,Zhai Yonghua,Yu Zuochong
Background Osteosarcoma (OS) is the most prevalent primary malignant bone tumor. However, single-agent chemotherapy exhibits limited efficacy against OS and often encounters tumor resistance. Therefore, we designed and constructed an integrated treatment strategy of photothermal therapy (PTT) combined with chemotherapy and used a surface-encapsulated platelet-osteosarcoma hybrid membrane (OPM) that enhances circulation time and enables OS-specific targeting. Results The OPM functions as a shell structure, encapsulating multiple drug-loaded nanocores (BPQDs-DOX) and controlling the release rate of doxorubicin (DOX). Moreover, near-infrared light irradiation accelerates the release of DOX, thereby extending circulation time and enabling photostimulation-responsive release. The OPM encapsulation system improves the stability of BPQDs, enhances their photothermal conversion efficiency, and augments PTT efficacy. In vitro and ex vivo experiments demonstrate that BPQDs-DOX@OPM effectively delivers drugs to tumor sites with prolonged circulation time and specific targeting, resulting in superior anti-tumor activity compared to single-agent chemotherapy. Furthermore, these experiments confirm the favorable biosafety profile of BPQDs-DOX@OPM. Conclusions Compared to single-agent chemotherapy, the combined therapy using BPQDs-DOX@OPM offers prolonged circulation time, targeted drug delivery, enhanced anti-tumor activity, and high biosafety, thereby introducing a novel approach for the clinical treatment of OS.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLINICAL LABORATORY ANALYSIS
·
2022
·Vol. 36
·期 11
·e24698
·
IF 3.124
Chunfa Chen,Liang Liu
Background Osteosarcoma (OS) is a highly recurrent malignancy occurring among adolescents. The goal of this research was to scrutinize the role and action mechanism of KLF3-AS1 in OS. Methods Western blotting and quantitative reverse transcription real-time PCR were conducted to ascertain the mRNA expressions of miR-338-3p, KLF3-AS1, and MEF2C in OS cell lines and tissue samples. Colony formation and CCK-8 experiments were done to evaluate the proliferative capacity of the cells. Western blotting was also executed to measure the relative expressions of the proteins Bcl-2 and Bax. RNA immunoprecipitation and dual luciferase reporter experiments were carried out to validate the target relationships among MEF2C, KLF3-AS1, and miR-338-3p. Mouse xenograft models were created to assess the influences of KLF3-AS1 on the growth of tumors in vivo. Results Elevated levels of KLF3-AS1 and MEF2C and reduced amounts of miR-338-3p were identified in OS. KLF3-AS1 targeted miR-338-3p, and miR-338-3p further targeted MEF2C. Silencing KLF3-AS1 induced apoptosis and attenuated proliferation in vitro and repressed the tumor growth in vivo. Inhibiting miR-338-3p inverted the cancer-suppressing effects of KLF3-AS1 silencing. Meanwhile, loss of MEF2C partially eliminated the effects brought about by miR-338-3p downregulation, namely the stimulation of cell growth and suppression of apoptosis. Conclusions Silencing of KLF3-AS1 could repress the growth of cells and induce apoptosis by regulating miR-338-3p/MEF2C in OS. This suggests that the regulatory axis KLF3-AS1/miR-338-3p/MEF2C is a prospective target for OS treatment.
研究领域:
肿瘤学
·
分子生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2023
·
IF 5
Jiangbo Nie,Yuhang Ling,Mingchao Jin,Zhuo Chen,Wei Liu,Weiyun Shen,Tianshun Fang,Jianyou Li,Ying He
Osteosarcoma (OS) is a highly fatal bone tumor characterized by high degree of malignancy and early lung metastasis. Traditional chemotherapy fails in improving the efficacy and survival rate of patients with OS. Butyrate (NaBu) has been reported as a new antitumor drug for inhibiting proliferation and inducing apoptosis in various cancer cells. However, the effect of NaBu on the ferroptosis of osteosarcoma is still unknown. This study aimed to investigate whether NaBu promotes erastin-induced ferroptosis in OS cells and to uncover the underlying mechanism. Here, we found that NaBu significantly enhanced erastin-induced ferroptosis in vitro . Compared with the group that erastin used alonely, pre-treating with NaBu exacerbated erastin-meditated GSH depletion, lipid peroxidation, and mitochondrial morphologic changes in OS cells. In a subcutaneous OS model, NaBu combined with erastin significantly reduced tumor growth and increased the levels of 4-HNE. Mechanistically, NaBu downregulated SLC7A11 transcription via regulating ATF3 expression. Overexpression of ATF3 facilitated erastin to induce ferroptosis, while ATF3 knockdown attenuated NaBu-induced ferroptosis sensitivity. In conclusion, our findings revealed a previously unidentified role of NaBu in erastin-induced ferroptosis by regulating SLC7A11, suggesting that NaBu may be a potential therapeutic agent for OS treatment.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
·
2021
·Vol. 18
·期 12
·2531-2538
·
IF 0.533
Jun Tang,Jingfang Yang
Purpose: To investigate the potential role of curcumin in osteosarcoma (OS) cell migration and invasion, and also to explore the underlying mechanism of action.
Methods: OS cell lines, Saos-2 and U2OS, were treated with various concentrations of curcumin (0, 10, 20, 50 μM) for 48 h. Transwell assay was used to determine the migratory and invasive activities of human OS cells while miR-33b-5p expression levels were measured using quantitative real time polymerase chain reaction (qRT-PCR). Expressions of metastasis-related genes, such as matrix metalloproteinases (MMPs), were quantified by qRT-PCR or western blot. The interaction between miR33b-5p and Sirtuin 6 (SIRT6) was evaluated by luciferase assay.
Results: Curcumin inhibited the migratory and invasive activities of huamn OS cells, and downregulated MMP2 and MMP9 (p < 0.05). Moreover, in curcumin-treated OS cells, miR-33b-5p expression was upregulated while SIRT6 expression was significantly downregulated (p < 0.05). Overexpression of miR-33b-5p downregulated SIRT6 mRNA and protein expression, whereas transfection with miR-33b-5p inhibitor upregulated SIRT6 expression in OS cells (p < 0.05). Furthermore, curcumin suppressed SIRT6 expression by upregulating miR-33b-5p expression in OS cells. Finally, overexpression of SIRT6 or miR-33b-5p inhibitor reversed the suppression of OS cell metastasis induced by curcumin (p < 0.05).
Conclusion: Curcumin inhibits SIRT6 expression via upregulating miR-33b-5p expression, which leads to the inhibition of OS cell migration and invasion. Thus, curcumin is a potential therapeutic agent for the management of OS.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Jinfeng Liao,Kun Shi,Yanpeng Jia,Yanting Wu,Zhiyong Qian
Osteosarcoma is a malignant bone tumor, which often occurs in adolescents. However, surgical resection usually fails to completely remove the tumor clinically, which has been the main cause of postoperative recurrence and metastasis, resulting in the high death rate of patients. At the same time, osteosarcoma invades a large area of the bone defect, which cannot be self-repaired and seriously affects the life quality of the patients. Herein, a bifunctional methacrylated gelatin/methacrylated chondroitin sulfate hydrogel hybrid gold nanorods (GNRs) and nanohydroxyapatite (nHA), which possessed excellent photothermal effect, was constructed to eradicate residual tumor after surgery and bone regeneration. In vitro , K7M2wt cells (a mouse bone tumor cell line) can be efficiently eradicated by photothermal therapy of the hybrid hydrogel. Meanwhile, the hydrogel mimics the extracellular matrix to promote proliferation and osteogenic differentiation of mesenchymal stem cells. The GNRs/nHA hybrid hydrogel was capable of photothermal treatment of postoperative tumors and bone defect repair in a mice model of tibia osteosarcoma. Therefore, the hybrid hydrogel possesses dual functions of tumor therapy and bone regeneration, which shows great potential in curing bone tumors and provides a new hope for tumor-related bone complex disease.
研究领域:
生物材料
·
癌症治疗
·
组织工程
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2016
·
IF 2.326
Zhenhua Fang,Yanpeng Sun,Hong Xiao,Peng Li,Ming Liu,Fan Ding,Wusheng Kan,Runsheng Miao
Osteosarcoma is the most common primary malignant bone tumor in the pediatric age group, and chemotherapy directed by targeted nanoparticulate drug delivery system represents a promising approach for osteosarcoma treatment recently. Here, we designed and developed a novel DOX-loaded targeted polymeric micelle self-assembled from RGD-terminated poly(ethylene glycol)- block -poly (trimethylene carbonate) (RGD-PEG-PTMC) amphiphilic biodegradable block copolymer , for high-efficiency targeted chemotherapy of osteosarcoma. Notably, the RGD-installed DOX-loaded biodegradable polymeric micelle (RGD-DOX-PM) with drug loading efficiency of 57%–73% displayed a narrow distribution (PDI = 0.05–0.12) with average sizes ranging from 46 to 73 nm depending on the DOX loading content. The release amount of DOX from RGD-DOX-PM achieved 63% within 60 h under physiological condition. Interestingly, MTT assays in MG-63 and MNNG/HOS osteosarcoma cells exhibited that half-maximal inhibitory concentration (IC 50 ) value of RGD-DOX-PM was much lower than its non-targeted counterpart (DOX-PM), implying RGD decorated nanoparticles had enhanced cell targeting ability and led to more effective anti-tumor effect. Furthermore, the targeting ability of RGD-DOX-PM was confirmed by in vitro flow cytometry and confocal laser scanning microscopy (CLSM) imaging assays, where the results showed more RGD-DOX-PM were taken up by MG-63 cells than that of DOX-PM. Therefore, this RGD decorated DOX-loaded polymeric micelle is promising for targeted chemotherapy of osteosarcoma.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Runzhi Xia,Wei Sun,Jiaming Liang,Shidong Wang,Fuqiang Gao,Yawei Liu,Liu Wang,Hongjie Zhang,Chao Ma,Kai Liu
The treatment of osteosarcoma remains challenging due to limitations of chemotherapy. Anticancer peptides present a promising avenue as alternative therapeutic agents; however, they encounter significant drawbacks, including susceptibility to proteolytic degradation and constrained selectivity toward tumor. Herein, a few-shot peptide screening strategy is developed, yielding identification of RT2 (tumor-lytic peptide) and E16 (ionic-responsive self-assembling peptide). Their fusion E16-RT2 (ER) is engineered, exhibiting 175% enhanced tumor-selective cytotoxicity and cancer membrane targeting. By leveraging the dual functionality of ER, an injectable hydrogel encapsulating doxorubicin is developed, enabling gradient dynamics for tumor-specific drug release and sustained therapeutic efficacy (>9 d). Moreover, there is no systemic/organ toxicity in murine models dosed with the therapeutic network. The potential mechanism is proposed: charge-guided ER localization disrupts cancer membrane integrity, enabling therapeutics influx while sparing healthy cells, coupled with network degradation kinetics ensuring prolonged drug retention. This rational design paradigm establishes a clinically translatable platform combining tumor-perturbing peptides with smart biomaterials, effectively overcoming limitations of conventional agents. The demonstrated “safety-efficacy” profile positions this approach as a viable strategy for cancer treatment.
研究领域:
肿瘤学
·
药理学
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Chao Xie,Qili Sun,Jingle Chen,Bingsheng Yang,Huiwen Lu,Zhanpeng Liu,Yucong Li,Kai Li,Bin Tang,Lijun Lin
Cuproptosis affects osteosarcoma locally, and the exploitation of cuproptosis-related biomaterials for osteosarcoma treatment is still in its infancy. We designed and synthesized a novel injectable gel of Cu ion–coordinated Tremella fuciformis polysaccharide (TFP–Cu) for antiosteosarcoma therapy. This material has antitumor effects, the ability to stimulate immunity and promote bone formation, and a controlled Cu 2+ release profile in smart response to tumor microenvironment stimulation. TFP–Cu can selectively inhibit the proliferation of K7M2 tumor cells by arresting the cell cycle and promoting cell apoptosis and cuproptosis. TFP–Cu also promoted the M1 polarization of RAW264.7 cells and regulated the immune microenvironment. These effects increased osteogenic gene and protein expression in MC3T3-E1 cells. TFP–Cu could significantly limit tumor growth in tumor-bearing mice by inducing tumor cell apoptosis and improving the activation of anti-CD8 T cell-mediated immune responses. Therefore, TFP–Cu could be a potential candidate for treating osteosarcoma and bioactive drug carrier for further cancer-related applications.
研究领域:
生物材料学
·
肿瘤学
·
免疫学
·
骨再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Tianjing Bao,Jian Ren,Yiyuan Wu,Yang Cao,Haobo Pan,Chunlin Deng
The repair of bone defects caused by osteosarcoma is still a significant clinical issue, and new scaffolds need to be developed to solve this problem. The ocean is a treasure trove for developing new biomedical materials, coral is widely thought to be suitable as a scaffold for bone implant material due to its porous structure and mechanical properties. Selenium is known for their antioxidant and antitumor effects, inducing tumor cell cycle arrest. In this study, we hydrothermally transformed corals to grow a hydroxyapatite layer on the scaffold surface (CHAp) and combined it with selenium to obtain selenium-doped scaffolds (Se-CHAp) without affecting the porous structure of the coral. The research successfully validates their biocompatibility and the antitumor efficacy against 143B osteosarcoma cells. The results indicate that the Se-CHAp scaffold yielded an obvious inhibitory effect on the proliferation of osteosarcoma cells, highlighting that it has huge prospects for application in biomedical technology.
研究领域:
生物医学工程
·
材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2024
·Vol. 29
·期 2
·83
·
IF 3.3
Linbang Wang,Xinyu Dou,Linzhen Xie,Xuchang Zhou,Yu Liu,Jingkun Liu,Xiaoguang Liu
Background: Lactic acid, previously regarded only as an endpoint of glycolysis, has emerged as a major regulator of tumor invasion, growth, and the tumor microenvironment. In this study, we aimed to explore the reprogramming of lactic acid metabolism relevant to osteosarcoma (OS) microenvironment by decoding the underlying lactic acid metabolic landscape of OS cells and intercellular signaling alterations. Methods: The landscape of OS metabolism was evaluated using single-cell gene expression data, lactic acid metabolism clustering, and screening of the hub genes in lactic acid metabolism of OS samples using transcriptome data. The role of the hub gene NADH:Ubiquinone Oxidoreductase Complex Assembly Factor 6 (NDUFAF6) was validated with in vitro studies and patient experiments. Results: Single-cell RNA sequencing data validated a lactic acid metabolismhigh subcluster in OS. Further investigation of intercellular communications revealed a unique metabolic communication pattern between the lactic acid metabolismhigh subcluster and other subclusters. Next, two lactic acid metabolic reprogramming phenotypes were defined, and six lactic acid metabolism-related genes (LRGs), including the biomarker NDUFAF6, were screened in OS. In vitro studies and patient experiments confirmed that NDUFAF6 is a crucial lactic acid metabolism-associated gene in OS. Conclusions: The patterns of lactic acid metabolism in OS suggested metabolic reprogramming phenotypes relevant to the tumor microenvironment (TME) and identified NDUFAF6 as an LRG prognostic biomarker.
研究领域:
肿瘤学
·
代谢生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）