This study investigates therapeutic efficacy of photothermal therapy (PTT) in an orthotropic xenograft model of bone metastasis of breast cancer. The near-infrared (NIR) irradiation on Multi-Walled Carbon Nanotubes (MWNTs) resulted in a rapid heat generation which increased with the MWNTs concentration up to 100 μg/ml. MWNTs alone exhibited no toxicity, but inclusion of MWNTs dramatically decreased cell viability when combined with laser irradiation. Thermographic observation revealed that treatment with 10 μg MWNTs followed by NIR laser irradiation resulted in a rapid increase in temperature up to 73.4±11.98 °C in an intraosseous model of bone metastasis of breast cancer. In addition, MWNTs plus NIR laser irradiation caused a remarkably greater suppression of tumor growth compared with treatment with either MWNTs injection or NIR irradiation alone, significantly reducing the amount of tumor-induced bone destruction. All these demonstrate the efficacy of PTT with MWNTs for bone metastasis of breast cancer.

The present study aimed to investigate candidate genes involved in the development and metastasis of osteosarcoma. Candidate genes were screened preliminarily from the Gene Expression Omnibus database and then validated using actual tumor tissues collected from patients with osteosarcoma. The cells were prepared and transfected with specific gene-targeted small interfering RNA followed by an MTS assay for cell viability detection and Transwell assays for cell migration and invasion capacity detection. The cell apoptosis was determined by flow cytometry and the protein level of the genes was detected by western blot analysis. An in vivo nude model was used and injected with cells to detect the functions of the genes. Transcriptome sequencing was performed to verify the regulation network, followed by reverse transcription-quantitative polymerase chain reaction and western blot analyses for validation. Increased tripartite motif-containing protein 2 (TRIM2) was detected in the osteosarcoma tumor tissues compared with normal tissues. The inhibition of TRIM2 induced lower cell viability and cell invasion capacity, and increased the rate of cell apoptosis. Decreased TRIM2 also inhibited the development and metastasis of osteosarcoma in the nude mouse models. The transcriptome sequencing revealed that the regulation of TRIM2 may be correlated with genes, Sirtuin 4, DNA damage inducible transcript 3, cAMP responsive element binding protein 5, G protein-coupled receptor 65 (GPR65) and ADP-ribosyltransferase 5. Western blot analysis indicated that TRIM2 regulated the development and metastasis of osteosarcoma via the phosphoinositide 3-kinase/protein kinase B signaling pathway. Therefore, TRIM2 performs important functions in regulating the development and metastasis of osteosarcoma.

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BackgroundParathyroid hormone (PTH) is an effective anti-osteoporosis agent, after binding to its receptor PTHR1, several signaling pathways, including cAMP/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC), are initiated through G proteins; with the cAMP/PKA pathway as the major pathway. Earlier studies have reported that PTHR1 might also activate PKC via a PLC-independent mechanism, but this pathway remains unclear.Material/MethodsIn HEK293 cells, cAMP accumulation was measured with ELISA and PKC was measured with fluorescence resonance energy transfer (FRET) analysis using CKAR plasmid. In MC3T3-E1 cells, real-time PCR was performed to examine gene expressions. Then assays for cell apoptosis, cell differentiation, alkaline phosphatase activity, and mineralization were performed.ResultsThe FRET analysis found that PTH(1–34), [G1,R19]PTH(1–34) (GR(1–34), and [G1,R19]PTH(1–28) (GR(1–28) were all activated by PKC. The PKC activation ability of GR(1–28) was blocked by cAMP inhibitor (Rp-cAMP) and rescued with the addition of active PKA-α and PKA-β. The PKC activation ability of GR(1–34) was partially inhibited by Rp-cAMP. In MC3T3-E1 cells, gene expressions of ALP, CITED1, NR4a2, and OSX that was regulated by GR(1–28) were significantly changed by the pan-PKC inhibitor Go6983. After pretreatment with Rp-cAMP, the gene expressions of ALP, CITED1, and OPG were differentially regulated by GR(1–28) or GR(1–34), and the difference was blunted by Go6983. PTH(1–34), GR(1–28), and GR(1–34) significantly decreased early apoptosis and augmented osteoblastic differentiation in accordance with the activities of PKA and PKC.ConclusionsPLC-independent PKC activation induced by PTH could be divided into two potential mechanisms: one was PKA-dependent and associated with PTH(1–28); the other was PKA-independent and associated with PTH(29–34). We also found that PTH could activate PLC-independent PKC via PKA-dependent mechanisms.

Background Icariin (ICA) can promote the migration and bone formation of bone marrow mesenchymal stem cells. This study explored a potential role of ICA in recruiting stem cell niches (SCNs) within the intervertebral disc region (ISN)-derived stem cells (ISN-SCs) to treat intervertebral disc degeneration (IVDD). Materials and methods EdU staining, transwell, and wound healing tests were used to analyze the function of ICA on ISN-SCs proliferation and migration ability. Simultaneously, the IVDD rat model was constructed by the acupuncture and divided into Sham, Sham + ICA, IVDD, and IVDD + ICA groups. H&E and PAS staining were performed to detect the pathological changes of IVDD tissues. Immunofluorescence was performed to discover relevant marker expression on the surface of stem cells in the IVDD tissues. Western blot and qPCR were executed to find the protein and mRNA expression of related cytokines in the IVDD tissues. Results ISN-SCs treated with 1 μM ICA obtained the better ability of proliferation and migration. H&E staining showed that the annulus fibrosus in the IVDD group was obviously hyperplasia with cavities and fissures; the nucleus pulposus was reduced. PAS staining showed that the content of polysaccharides was significantly reduced in the nucleus pulposus of IVDD group. However, the ICA treatment alleviated the pathological trends of the IVDD tissues. Simultaneously, ICA treatment increased significantly the expression of stem cells and IGF-1, TGF-β, SDF-1, CCL-5, Collagen I, Collagen II, Aggrecan, and SOX9 in IVDD tissues. Conclusions ICA treatment promoted the migration of stem cell in IVDD by increasing the expression of chemotactic cytokines, including IGF-1, TGF-β, SDF-1, and CCL-5.

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Background The role of gene and pathway in recurrence of Ewing sarcoma (ES) was not clear. Thus, we investigated the biological role and underlying mechanism of gene and pathway in recurrence of ES.Methods Data sets of patients with ES were collected from the GEO database. We used dataset GSE63155 and GSE63156 to construct co-expression networks by weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). ResultsWe can find that genes with significant interactions in the genes of the recurrence group include SRSF11, TRIM39, SOCS3,NUPL2,COPS5. They work primarily through the oxidative stress pathway.Conclusion Through our research, for the first time found that ES by SRSF11 TRIM39, SOCS3, NUPL2, COPS5 interaction, activation of phosphorylation of bone and oxidative stress is affecting tumor recurrence. 4.SelvanathanSP, Graham GT, Grego AR, Baker TM, Hogg JR, Simpson M, Batish M, Crompton B, Stegmaier K, Tomazou EM et al: EWS-FLI1 modulated alternative splicing of ARID1A reveals novel oncogenic function through the BAF complex. Nucleic acids research 2019, 47(18):9619-9636. 5. Zhang B, Horvath S: A general framework for weighted gene co-expression network analysis. Statistical applications in genetics and molecular biology 2005, 4:Article17. 6. The Gene Ontology (GO) project in 2006. Nucleic acids research 2006, 34(Database issue):D322-326. 7. Dwight SS, Eppig JT et al: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nature genetics 2000, 25(1):25-29.8.