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

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in cancer development and progression. However, the mechanism by which they enhance the chemoresistance of ovarian cancer is unknown. METHODS: Conditioned media of BM-MSCs (BM-MSC-CM) were analyzed using a technique based on microRNA arrays. The most highly expressed microRNAs were selected for testing their effects on glycolysis and chemoresistance in SKOV3 and COC1 ovarian cancer cells. The targeted gene and related signaling pathway were investigated using in silico analysis and in vitro cancer cell models. Kaplan-Merier survival analysis was performed on a population of 59 patients enrolled to analyze the clinical significance of microRNA findings in the prognosis of ovarian cancer. RESULTS: MiR-1180 was the most abundant microRNA detected in BM-MSC-CM, which simultaneously induces glycolysis and chemoresistance (against cisplatin) in ovarian cancer cells. The secreted frizzled-related protein 1 (SFRP1) gene was identified as a major target of miR-1180. The overexpression of miR-1180 led to the activation of Wnt signaling and its downstream components, namely Wnt5a, β-catenin, c-Myc, and CyclinD1, which are responsible for glycolysis-induced chemoresistance. The miR-1180 level was inversely correlated with SFRP1 mRNA expression in ovarian cancer tissue. The overexpressed miR-1180 was associated with a poor prognosis for the long-term (96-month) survival of ovarian cancer patients. CONCLUSIONS BM-MSCs enhance the chemoresistance of ovarian cancer by releasing miR-1180. The released miR-1180 activates the Wnt signaling pathway in cancer cells by targeting SFRP1. The enhanced Wnt signaling upregulates the glycolytic level (i.e. Warburg effect), which reinforces the chemoresistance property of ovarian cancer cells.
Adenosine Triphosphate/chemistry* ; Adult ; Aged ; Bone Marrow Cells/cytology* ; Cell Line, Tumor ; Cell Proliferation ; Cells, Cultured ; Drug Resistance, Neoplasm/genetics* ; Female ; Flow Cytometry ; Follow-Up Studies ; Glycolysis ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism* ; Membrane Proteins/metabolism* ; Mesenchymal Stem Cells/cytology* ; MicroRNAs/genetics* ; Middle Aged ; Multivariate Analysis ; Ovarian Neoplasms/genetics* ; Up-Regulation ; Wnt Signaling Pathway

OBJECTIVE: The aim of the study was to compare the diagnostic performances of F-18 sodium fluoride positron emission tomography/computed tomography (bone PET/CT) and bone scintigraphy (BS) for the detection of thyroid cancer bone metastasis. MATERIALS AND METHODS: We retrospectively enrolled 6 thyroid cancer patients (age = 44.7 ± 9.8 years, M:F = 1:5, papillary:follicular = 2:4) with suspected bone metastatic lesions in the whole body iodine scintigraphy or BS, who subsequently underwent bone PET/CT. Pathologic diagnosis was conducted for 4 lesions of 4 patients. RESULTS: Of the 17 suspected bone lesions, 10 were metastatic and 7 benign. Compared to BS, bone PET/CT exhibited superior sensitivity (10/10 = 100% vs. 2/10 = 20%, p = 0.008), and accuracy (14/17 = 82.4% vs. 7/17 = 41.2%, p < 0.025). The specificity (4/7 = 57.1%) of bone PET/CT was not significantly different from that of BS (5/7 = 71.4%, p > 0.05). CONCLUSION: Bone PET/CT may be more sensitive and accurate than BS for the detection of thyroid cancer bone metastasis.
Adult ; Bone Neoplasms/*radiography/secondary ; Bone and Bones/*radiography ; Contrast Media/*chemistry ; Female ; Fluorine Radioisotopes/chemistry ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; Retrospective Studies ; Sodium Fluoride/*chemistry ; Thyroid Neoplasms/*pathology ; Tomography, X-Ray Computed ; Whole Body Imaging

No abstract available.
Aged ; Biomarkers, Tumor/analysis ; Biopsy, Large-Core Needle ; Bone Neoplasms/chemistry/radiotherapy/*secondary ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/chemistry/*pathology/surgery ; Pneumonectomy ; Positron-Emission Tomography ; Pulmonary Sclerosing Hemangioma/chemistry/radiotherapy/*secondary/surgery ; Tomography, X-Ray Computed ; Treatment Outcome

BACKGROUNDCavity reconstruction after benign bone tumor removal is varied and controversial. Allograft is widely used but is associated with complications. New bone substitutes, such as calcium sulfate artificial bone, have been introduced for bone tumor operation. However, the bone healing response of artificial bone has not been compared with allograft bone. We therefore compared calcium sulfate grafts (study group) with bone allografts (control group) for the treatment of benign bone tumors.

METHODSWe retrospectively reviewed 50 patients who underwent calcium sulfate reconstruction and 50 patients who underwent allograft cancellous bone reconstruction. The two groups were well matched. The mean follow-up time of the study group was 19.9 (12-55) months. We investigated bone healing response, complications, and factors affecting bone healing.

RESULTSAt the last follow-up, 84% (42/50) of cases in the study group and 62% (31/50) of cases in the control group had achieved clinical healing (P = 0.013). The initial healing rate showed no significant difference between the two groups (100% vs. 96%, P = 0.153). The mean healing times for calcium sulfate and allograft bone were 9.6 (3-42) months and 13.8 (3-36) months, respectively (P < 0.01). Complications in the study group were minor and resolved. Implant volume was a significant factor affecting bone healing.

CONCLUSIONThe calcium sulfate bone substitute showed a satisfactory healing outcome and safety profile in reconstruction of bone defects after benign bone tumor curettage, especially in smaller cavities.

Adolescent ; Adult ; Aged ; Allografts ; Bone Neoplasms ; surgery ; Calcium Sulfate ; chemistry ; Child ; Curettage ; methods ; Female ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Retrospective Studies ; Young Adult

To develop standard in vitro chondrosarcoma models, we synthesized three hydrogels (i. e., PDMAAm, PNaAMPS and PMETAC) and investigated the influence of Young's modulus, swelling ratio and electric charges on the behavior of chondrosarcoma cells seeded on the hydrogels, including morphology, adhesion and aggregation. Results showed that the morphology of chondrosarcoma cells at 6h was dependent on the charges of hydrogels; cells present spindle-shaped and round-shaped morphology on negative charged and neutral hydrogel, respectively, while no cells spreaded on positive charged hydrogel. Chondrosarcoma cells formed aggregates on neutral PDMAAm after further culture. The hydrogels can be synthesized easily and has the characteristics of ease at use with defined components, which holds great potential for developing standard chondrosarcoma models in vitro.
Bone Neoplasms ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chondrosarcoma ; pathology ; Humans ; Hydrogels ; chemistry ; pharmacology ; Methacrylates ; pharmacology ; Nylons ; pharmacology ; Static Electricity

OBJECTIVETo investigate the effect of minocycline hydrochloride ointment on cell attachment and proliferation on titanium disks.

METHODSCommercially pure (grade 4) machined titanium discs with three different kinds of surfaces (smooth, acid-etched and sandblasted combined with acid-etched) were treated with minocycline ointment for 1 week, and then cleaned in ultrasonic cleanser for 10 minutes. Surface properties were examined by scanning electron microscope (SEM) and roughness tester before and after the treatment. Surface roughness was compared by paired t test. MG-63 (human osteoblast-like osteosarcoma cell) cells were seeded on these three kinds of discs with or without minocycline treatment, and methl thiazolyl tetrazolium (MTT) was performed to investigate the attachment in the 1st day and proliferation in the 4th and 7th day. Data were analyzed by double factor analysis of variance.

RESULTSSurface roughness before and after minocycline application was as follows, Smooth: (0.093 ± 0.025) µm, (0.086 ± 0.026) µm; Acid-etched: (1.100 ± 0.095) µm, (1.009 ± 0.196) µm; Sandblasted combined with acid-etched: (2.837 ± 0.283) µm, (2.968 ± 0.206) µm. No significant changes in roughness were found before and after minocycline application (P values were 0.118, 0.436 and 0.692). SEM examination revealed as similar surface configuration after minocycline application as before, except for some remnant of the minocycline ointment in acid-etched and sandblasted combined acid-etched groups. In MTT test, the growth of MG-63 cells in the 1 st, 4th day and 7th day was not different between groups with and without minocycline application (P values were 0.450, 0.848 and 0.835), and among three groups of different surface (P values were 0.184, 0.579 and 0.331).

CONCLUSIONSMinocycline hydrochloride ointment did not affect the surface configuration, surface roughness or the properties for cell attachment and proliferation of titanium discs.

Acid Etching, Dental ; Bone Neoplasms ; pathology ; Cell Adhesion ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Microscopy, Electron, Scanning ; Minocycline ; administration & dosage ; pharmacology ; Ointments ; Osteoblasts ; pathology ; Osteosarcoma ; pathology ; Surface Properties ; Titanium ; chemistry

With IL-6R as target, a new compound 2460A was identified from fungus using HTS screening model. The taxonomics of the produced strain was confirmed to be Trichoderma hazianum rifai after sequencing analysis of rDNA-ITS (internal transcribed spacer). Results showed that this compound has a binding activity on IL-6R competed with IL-6, thus it is a new ligand of IL-6R originating from microbe. With MTT assay, the anti-tumor activities of 2460A were demonstrated on CM126 and HT-29 cell lines separately, the IC50 are 2.17 x 10(-5) mol x L(-1) and 1.8 x 10(-5) mol x L(-1) respectively. The compound affected lightly the HT-29 cell cycle at S phase. Studies for the anti-tumor activity of 2460A in vivo are in progress in our lab.
Antineoplastic Agents ; isolation & purification ; metabolism ; pharmacology ; Binding, Competitive ; Bone Marrow Neoplasms ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; HT29 Cells ; High-Throughput Screening Assays ; Humans ; Interleukin-6 ; metabolism ; Ligands ; Receptors, Interleukin-6 ; metabolism ; Trichoderma ; chemistry

Age Factors ; Bone Neoplasms ; secondary ; Breast Neoplasms ; chemistry ; genetics ; pathology ; Carcinoma, Ductal, Breast ; chemistry ; genetics ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; chemistry ; genetics ; pathology ; Female ; Gene Expression Profiling ; Humans ; Ki-67 Antigen ; analysis ; Lymphatic Metastasis ; Prognosis ; Receptor, ErbB-2 ; analysis ; Receptors, Estrogen ; analysis ; Receptors, Progesterone ; analysis ; Tumor Burden