The efficacy and specificity of treatment are the major challenges for cancer gene therapy. Oncolytic virotherapy is an attractive drug delivery platform of cancer gene therapy. Previous studies have determined that apoptin is a p53-independent, Bcl-2-insensitive apoptotic protein that has the ability to induce apoptosis specifically in tumor cells. In this study, we show that the administration of a dual cancer-specific oncolytic adenovirus construct, Ad-hTERT-E1a-apoptin [in which the adenovirus early region 1a (E1a) gene is driven by the cancer-specific promoter of human telomerase reverse transcriptase (hTERT) and that expresses apoptin simultaneously], suppresses tumor growth in gastric carcinoma cells in vitro and reduces the tumor burden in vivo in xenografted nude mice. The observation that infection with the Ad-hTERT-E1a-apoptin construct significantly inhibited the growth of gastric cancer cells and protected normal human gastric epithelium from growth inhibition confirmed the induction of cancer cell-selective adenovirus replication, growth inhibition and apoptosis by this therapeutic approach. In vivo assays were performed using BALB/c nude mice that had established primary tumors. Subcutaneous primary tumor volume was reduced not only in the intratumoral injection group but also in the systemic delivery mice following treatment with Ad-hTERT-E1a-apoptin. Furthermore, treatment of primary models with Ad-hTERT-E1a-apoptin increased the mouse survival time. These data reinforce previous research and highlight the potential therapeutic application of Ad-hTERT-E1a-apoptin for the treatment of neoplastic diseases in clinical trials.
Osteosarcoma (OS) is one of the most common primary solid malignant tumors in orthopedics, and its main clinical treatments are surgery and chemotherapy. However, a wide surgical resection range, functional reconstruction of postoperative limbs, and chemotherapy resistance remain as challenges for patients and orthopedists. To address these problems, the discovery of new effective conservative treatments is important. Long non-coding RNAs (lncRNAs) are RNAs longer than 200 nucleotides in length that do not encode proteins. Researchers have recently found that long non-coding RNAs are closely associated with the development of OS, indicating their potentially vital role in new treatment methods for OS. This review presents new findings regarding the association of lncRNAs with OS and summarizes potential clinical applications of OS with lncRNAs, including the downregulation of oncogenic lncRNAs, upregulation of tumor suppressive lncRNAs, and lncRNAs-based treatment to improve chemotherapy resistance. We hope these potential methods will be translated into clinical applications and greatly reduce patient suffering.
Background Periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) is a serious complication for patients. Some joint surgeons have tried to use vancomycin powder (VP) in total knee and total hip arthroplasty to prevent postoperative PJI, but its effect is still not clear. At present, there is no meta-analysis that specifically analyses the effect of different doses of vancomycin powder on the incidence of PJI. Methods We carried out a search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and identified the studies we needed. Review Manager (RevMan) 5.3 software was employed for statistical analysis. Results The analysis of primary TKA (PTKA) showed that using 1 g (RR 0.38, 95% CI 0.22–0.67 [P = 0.0008]) and 2 g (RR 0.48, 95% CI 0.31–0.74 [P = 0.0008]) of vancomycin powder in primary TKA (PTKA) could all significantly prevent PJI. The analysis of primary THA (PTHA) showed that using 1 g (RR 0.37, 95% CI 0.17–0.80 [P = 0.01]) of vancomycin powder effectively decreased the incidence of PJI, while using 2 g (RR 1.02, 95% CI 0.53–1.97 [P = 0.94]) of vancomycin powder had no significant effect on preventing PJI. Because the data were abnormal, we believed the conclusion that using 2 g of vancomycin powder in primary THA had no effect on preventing PJI was doubtful. Using vancomycin powder in revision TKA (RTKA) significantly reduced the PJI rate (RR 0.33, 95% CI 0.14–0.77 [P = 0.01]), similar to revision THA (RTHA) (RR 0.37, 95% CI 0.14–0.96 [P = 0.04]). Conclusions In primary TKA, both 1 g and 2 g of vancomycin powder can effectively prevent PJI. In primary THA, using 1 g of vancomycin powder is a better choice, while the effect of using 2 g of vancomycin powder is not clear, and a more prospective randomized controlled trial should be done to verify it. In revision TKA and revision THA, vancomycin powder is a good choice to prevent PJI.
The management and definitive treatment of critical-size bone defects in severe trauma, tumor resection and congenital malformation are troublesome for orthopedic surgeons and patients worldwide without recognized good treatment strategies. Researchers and clinicians are working to develop new strategies to treat these problems. This review aims to summarize the techniques used by additive manufacturing scaffolds loaded with BMP-2 to promote osteogenesis and to analyze the current status and trends in relevant clinical translation. Optimize composite scaffold design to enhance bone regeneration through printing technology, material selection, structure design and loading methods of BMP-2 to advance the clinical therapeutic bone repair field.
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