Bone marrow (BM)-derived hematopoietic cells, which are major components of tumor stroma, determine the tumor microenvironment and regulate tumor phenotypes. Cyclooxygenase (COX)؊2 and endogenous prostaglandins are important determinants for tumor growth and tumor-associated angiogenesis; however, their contributions to stromal formation and angiogenesis remain unclear. In this study, we observed that Lewis lung carcinoma cells implanted in wild-type mice formed a tumor mass with extensive stromal formation that was markedly suppressed by COX-2 inhibition, which reduced the recruitment of BM cells. Notably, COX-2 inhibition attenuated CXCL12/CXCR4 expression as well as expression of several other chemokines. Indeed, in a Matrigel model, prostaglandin (PG) E 2 enhanced stromal formation and CXCL12/CXCR4 expression. In addition, a COX-2 inhibitor suppressed stromal formation and reduced expression of CXCL12/CXCR4 and a fibroblast marker (S100A4) in a micropore chamber model. Moreover, stromal formation after tumor implantation was suppressed in EP3 ؊/؊ mice and EP4 ؊/؊ mice, in which stromal expression of CXCL12/ CXCR4 and S100A4 was reduced. The EP3 or EP4 knockout suppressed S100A4 Recent advances in tumor biology have identified the stroma as an important regulator of carcinogenesis and a potentially valuable therapeutic target. Although interactions between the epithelium and stroma have long been considered to be important in tumor progression, the efficacy of targeting stromal components as a therapeutic strategy has not been established, because the specific regulators of such interactions remain unclear. In addition to endothelial cells, macrophages and fibroblasts 1 are the major stromal components of the tumor microenvironment, and they play key roles in the enhancement of angiogenesis. It has recently been established that bone marrow (BM)-derived hematopoietic cells are the major components of the stroma of tumors, and that they determine the tumor microenvironment [2][3][4][5][6][7][8] ; however, the specific factors that enhance the functions of BM-derived precursor cells, and the mechanism of recruitment of these cells during tumor angiogenesis, are not fully understood. Tumor-associated angiogenesis in the tumor stroma is a prerequisite for invasive growth of a tumor larger than 2 to 3 mm in diameter, and then metas-
BSLs are a newly defined spinal MRI finding specifically seen in NMO. In combination with LESCL, BSLs can help differentiate patients with NMO from those with MS with higher sensitivity than LESCL alone.
E-type prostaglandins have been reported to be proangiogenic in vivo. Thus, we examined prostaglandin receptor signaling relevant to wound-induced angiogenesis. Full-thickness skin wounds were created on the backs of mice, and angiogenesis in wound granulation tissues was estimated. Wound closure and re-epithelization in EP3 receptor knockout mice (EP3 ؊/؊ ) were significantly delayed compared with their wild-type (WT) mice, whereas those in EP1 ؊/؊ , EP2 ؊/؊ , and EP4 ؊/؊ were not delayed. Wound-induced angiogenesis estimated with CD31 immunohistochemistry in EP3 ؊/؊ mice was significantly inhibited compared with that in WT mice. Immunoreactive vascular endothelial growth factor (VEGF) in wound granulation tissues in EP3 ؊/؊ mice was markedly less than that in WT mice. Wound closure in WT mice was delayed significantly by VEGF neutralizing antibody compared with control IgG. Wound-induced angiogenesis and wound closure were significantly suppressed in EP3 ؊/؊ bone marrow transplantation mice compared with those in WT bone marrow transplantation mice. These were accompanied with the reductions in accumulation of VEGF-expressing cells in wound granulation tissues and in mobilization of VEGF receptor 1-expressing leukocytes in peripheral circulation. These results indicate that the recruitment of EP3-expressing cells to wound granulation tissues is critical for surgical wound healing and angiogenesis via up-regulation of VEGF. (Am J Pathol
Study Design Vertebral fracture load and stiffness from a metastatic vertebral defect model were predicted using nonlinear finite element models (FEM) and validated experimentally. Objective The study objective was to develop and validate an FEM-based tool for predicting polymer-augmented lytic vertebral fracture load and stiffness and the influence of metastatic filling materials. Summary of Background Data Percutaneous vertebroplasty has the potential to reduce vertebral fracture risk affected with lytic metastases by providing mechanical stabilization. However, it has been shown that the mismatch in mechanical properties between poly(methyl-methacrylate) (PMMA) and bone induces secondary fractures and intervertebral disc degeneration. A biodegradable co-polymer, poly(propylene fumarate-co-caprolactone) [P(PF-co-CL)], has been shown to possess the appropriate mechanical properties for bone defect repair. Methods Simulated metastatic lytic defects were created in 40 cadaveric vertebral bodies, which were randomized into four groups: intact vertebral body (Intact), simulated defect without treatment (Negative), defect treated with P(PF-co-CL) (Co-polymer), and defect treated with PMMA (PMMA). Spines were imaged with quantitative computerized tomography (QCT), and QCT/FEM-subject-specific, non-linear models were created. Predicted fracture loads and stiffness were identified and compared to experimentally measured values using Pearson’s correlation analysis and paired t-test. Results There was no significant difference between the measured and predicted fracture loads and stiffness for each group. Predicted fracture loads were larger for PMMA-augmentation (3960 N (1371 N)) compared to that of the co-polymer, negative and intact groups (3484 N (1497 N), 3237 N (1744 N) and 1747 N (702 N)). A similar trend was observed in the predicted stiffness. Moreover, predicted and experimental fracture loads were strongly correlated (R2 = 0.78), while stiffness showed moderate correlation (R2 = 0.39). Conclusion QCT/FEM was successful for predicting fracture loads of metastatic, polymer-augmented vertebral bodies. Overall, we have demonstrated that QCT/FEM may be a useful tool for predicting in situ vertebral fracture load resulting from vertebroplasty.
Our computer-assisted method of measuring the tibio-femoral angle was simple, easy, and quick, and should be considered as an alternate method for measurement.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.