Distant metastasis, predominantly to bone, is the leading cause of morbidity and mortality in prostate cancer. However, the mechanisms underlying prostate cancer metastases remain unknown. Prostate cancer cells exhibited discrete adhesion to bone marrow endothelial cells (BMEC), resulting in osteotropic metastasis. Prior data showed an increased metastatic propensity of prostate stem cell antigen (PSCA)-positive prostate cancer cells. The current study sought to characterize the roles of PSCA in the adhesion of prostate cancer cells to BMECs. Cell adhesion was assessed using the adhesion assay and transendothelial migration. The expression and regulation of integrins were evaluated by qRT-PCR, Western blot, promoter-luciferase activity, and chromatin immunoprecipitation (ChIP). Functionally, the potential interacting partners of PSCA in prostate cancer cells were identified by coimmunoprecipitation and mass spectrometry (MS) analysis. The association of PSCA expression with bone metastasis was further analyzed in an in vivo model and prostate cancer patients. We found that overexpression of PSCA enhanced the adhesion capability of prostate cancer cells to BMECs through upregulating integrin-a4 expression, concurrent with transcriptionally activated NF-kB. Growth factor progranulin (PGRN) was identified as a potential interacting partner of PSCA in prostate cancer cells. Functional studies showed that downregulation of PGRN and PSCA with siRNAs in prostate cancer cells significantly suppressed the integrin-a4 expression and the adhesion to BMECs in vitro, respectively, which were restorable by exogenous PGRN. Importantly, PSCA depletion significantly reduced tumors' presence in the bone of a mouse model. Furthermore, PSCA expression is elevated in prostate cancer tissue, and significantly associated with increased Gleason score, advanced stage, bone metastasis, and poor prognosis in prostate cancer patients. We conclude that PSCA/PGRN promoted the adhesion of prostate cancer cells to BMECs through NF-kB/integrin-a4 pathways, to facilitate metastases. Implications: The findings presented here suggest PSCA/PGRN as a potential therapeutic target for prostate cancer metastases, especially for bone metastasis.
: Osteoarthritis (OA), characterized by the degeneration and destruction of articular cartilage, is one of the most significant public health issues around the world. In the course of OA, inflammatory response is an important factor leading to cartilage destruction and exacerbation of symptoms. The low immunogenicity, multi-directional differentiation and high portability properties make bone marrow mesenchymal stem cells (BMSCs) ideal seed cells for OA. Here, we review recent literature relating to the application of BMSCs for OA cell therapy and consider the following aspects: migration and homing of BMSCs, immunomodulatory and anti-inflammatory effects of BMSCs, anti-fibrotic effects of BMSCs, the application of biological scaffolds in cartilage regeneration by BMSCs and chondrogenic differentiation of BMSCs. Injecting BMSCs into joints with an inflammatory environment may increase the risk of osteoproliferation and ectopic calcification in patients. Further evidence and studies are needed to ensure the improvement and maintenance of the intraarticular environment for cartilage repair and regeneration.
Purpose: To evaluate whether serum neuroendocrine markers could effectively predict treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: The PubMed, Cochrane Library and Embase databases were sought to identify eligible studies concerning serum neuroendocrine markers and the prognosis of post-treatment mCRPC from inception to April 2018. The association between serum neuroendocrine markers, that is, chromogranin A (CgA) and neurone-specific enolase (NSE), levels and the prognosis of post-treatment mCRPC were summarized using a random-effects model and hazard ratio (HR) with 95% CI Sensitivity analyses were conducted to assess potential bias. Results: A total of 234 participants are included in this meta-analysis (mean age = 71.3 years) from 6 studies. The pooled results show that higher markers’ levels at baseline in patients were associated with unfavorable overall survival (OS; univariate analysis: HR 3.775, 95% CI 1.469–9.698, p = 0.006; multivariate analysis: HR 3.838, 95% CI 1.774–8.304, p = 0.001), and a similar situation was observed in progression-free survival (PFS; univariate analysis: HR 2.785, 95% CI 1.315–5.898, p = 0.007; multivariate analysis: HR 1.266, 95% CI 1.017–1.577, p = 0.035). Estimates of the total effects were generally consistent in the sensitivity analysis. Publication bias was observed when performing the univariate analysis of PFS, and we have the explanation accordingly. Conclusions: The results of this pooled analysis confirm serum neuroendocrine markers could be the effective predictor of treatment outcome in patients with mCRPC. In addition, a combination of CgA and NSE is more valuable to predict worse OS. Further randomized case-control trials are required to validate this relationship.
ObjectiveTo compare dorsal penile nerve block (DPNB) and eutectic mixture of local anesthetics (EMLA) cream for pain relief in infants during circumcision.MethodsWe systematically searched Medline via PubMed, Embase, CNKI and the Cochrane Library Center Register to identify randomized controlled trials up to March 2018. Effect estimates were performed in random effect models. Mean neonate infant pain scale (NIPS) scores, incidence of hematoma, edema and erythema, mean heart rate were conducted to assessed the effect of analgesia. We found that the EMLA had significantly higher pain scores compared to DPNB (SMD = 3.72, 95% CI 1.27–6.17, P = 0.003). In DPNB group, the incidence of hematoma was significantly higher than EMLA group, OR = 0.03, 95% CI 0.00–0.24, P = 0.001. The analysis did not show any significant differences in mean heart rate and the risk of edema and erythema between EMLA and DPNB group (SMD = 21.71, 95% CI = -0.88–44.30, P = 0.06 & OR = 0.40, 95% CI 0.15–1.07, P = 0.07 & OR = 7.33, 95% CI 0.84–64.07, P = 0.07).ConclusionBased on the pooled results from the included studies, we found that DPNB was significantly more effective in pain relief as indicated by mean NIPS score than EMLA in infants during circumcision. However, use of DPNB significantly increased the risk of hematoma.
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.