BackgroundRandomized controlled trials (RCTs) which are of poor quality tend to exaggerate the effect estimate and lead to wrong or misleading conclusions. The aim of this study is to assess the quality of randomization methods, allocation concealment and blinding within traditional Chinese medicine (TCM) RCTs, discuss issues identified for current TCM RCTs, and provide suggestions for quality improvement.MethodsWe searched Chinese Biomedical Database (CBM, 1978 to July 31, 2009) and the Cochrane Library (Issue 2, 2009) to collect TCM systematic reviews and meta-analyses according to inclusion/exclusion criteria, from which RCTs could be identified. The quality assessment involved whether the randomization methods, allocation concealment and blinding were adequate or not based the study reported. Stratified analyses were conducted of different types of diseases published in different journals (both Chinese and foreign) using different interventions. SPSS 15.0 software was used for statistic analyses.ResultsA total of 3159 RCTs were included, of which 2580 were published in Chinese journals and 579 in foreign journals. There were 381 (12%) RCTs which used adequate randomization methods; 207 (7%) RCTs which used adequate allocation concealment and 601 (19%) which used adequate blinding; there were 130 (4%) RCTs which both used adequate randomization methods and allocation concealment; and there were only 100 (3%) RCTs which used adequate randomization methods, allocation concealment, as well as blinding. In the RCTs published in foreign journals, the adequate randomization methods, allocation concealment and blinding accounted for a relatively large proportion (25%, 26%, and 60%, respectively) and increased with years, while in the RCTs published in Chinese journals, only the adequate randomization methods improved over time. The quality of non-drug intervention (chiefly acupuncture) RCTs was higher than that of drug intervention RCTs. In drug intervention, the quality of listed drugs is higher than the others. The quality of all included RCTs of all types of diseases was generally poor and no studies that were large in size and of high quality were found.ConclusionThe quality of the current TCM RCTs as judged by their publications is generally poor, especially those published in Chinese journals. In future, researchers of TCM RCTs should attach more importance to experimental design and methodological quality, receive relevant training, and improve reporting quality using the Consolidated Standards of Reporting Trials (CONSORT) statement, so as to improve the quality of TCM clinical research and ensure truth and reliability of conclusions.

Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells. The combination of FA-chitosan/mIP-10 and DC/tumor cell fusion vaccine against hepatocellular carcinoma (HCC) effectively inhibited the growth of implanted HCC tumors and prolonged the survival of mice. The combination therapy significantly reduced myeloid-derived suppressor cells (MDSC) in mouse spleen, local tumor, and bone marrow while increasing tumor-specific IFN-γ responses. Furthermore, the combination therapy significantly inhibited tumor cell proliferation while promoting their apoptosis. Taken together, our data illustrate that the mIP-10 enhances the anti-tumor effect of DC/tumor cell fusion vaccine by alleviating the immunosuppressive tumor environment.

This article reviews the preclinical research, clinical application and development of Newcastle disease virus (NDV) in the field of cancer therapy. Based on the distinctive antitumour properties of NDV and its positive interaction with the patient's immune system, this biologic could be considered a major breakthrough in cancer treatment. On one hand, NDV infection creates an inflammatory environment in the tumour microenvironment, which can directly activate NK cells, monocytes, macrophages and dendritic cells and promote the recruitment of immune cells. On the other hand, NDV can induce the upregulation of immune checkpoint molecules, which may break immune tolerance and immune checkpoint blockade resistance. In fact, clinical data have shown that NDV combined with immune checkpoint blockade can effectively enhance the antitumour response, leading to the regression of local tumours and distant tumours when injected, and this effect is further enhanced by targeted manipulation and modification of the NDV genome. At present, recombinant NDV and recombinant NDV combined with immune checkpoint blockers have entered different stages of clinical trials. Based on these studies, further research on NDV is warranted.

Background: Adoptive immunotherapy with cytotoxic T lymphocytes (CTLs) has great potential for the treatment of some malignant cancers. Therefore, augmenting the responses of tumor-specific CTLs is significant for the adoptive immunotherapy of melanoma. This study aimed to investigate the anti-tumor response of a combination therapy employing folate-modified chitosan nanoparticles containing IP-10 (interferon-γ-inducible protein-10) plus melanoma TRP2-specific CD8+CD28+ T cells. Methods: We prepared folate-modified chitosan nanoparticles containing the mouse IP-10 gene (FA-CS-mIP-10), and induced melanoma TRP2-specific CD8+CD28+ T cells by co-culturing them with artificial antigen-presenting cells. B16-bearing mice were treated with FA-CS-mIP-10, melanoma TRP2-specific CD8+CD28+ T cells, a combination of both, and the saline control. Tumor volumes and the survival time of mice were recorded. The proportion of myeloid-derived suppressor cells (MDSCs) infiltrating the tumor microenvironment and regulatory T cells (Tregs) in the spleen was analyzed by flow cytometry. We also detected the proliferation and angiogenesis of tumors by immunohistochemistry and apoptosis by TUNEL. Results: The combination therapy inhibited the progression of melanoma in vivo. Compared with other treatments, it more efficiently inhibited tumor growth and increased the survival time of mice. After treatment with combination therapy, the proportion of MDSCs and Tregs decreased, while the percentage of CXCR3+CD8+ T cells increased. Furthermore, combination therapy inhibited proliferation and promoted apoptosis of tumor cells and significantly inhibited tumor angiogenesis in vivo. Conclusion: We describe a novel strategy for improving the anti-tumor response of CD8+CD28+ CTLs by combining them with FA-CS-mIP-10 nanoparticles.

The current study is to develop a gentle and efficient method for purification of fibroblast-activation protein positive (FAP+) cancer-associated fibroblasts (CAFs) from tumor tissues. Fresh tissues were isolated from BALB/c-Nude mice bearing human liver cancer cell line (HepG2), fully minced and separated into three parts, and digested with trypsin digestion and then treated with collagenase type IV once, twice, or thrice, respectively. Finally, the cells were purified by using FAP magnetic beads. The isolated CAFs were grown in culture medium and detected for the surface expression of fibroblast-activation protein (FAP). The number of adherent cells which were obtained by digestion process with twice collagenase type IV digestion was (5.99 ± 0.18) × 104, much more than that with the only once collagenase type IV digestion (2.58 ± 0.41) × 104 (P < 0.0001) and similar to thrice collagenase type IV digestion. The percentage of FAP+ CAFs with twice collagenase type IV digestion (38.5%) was higher than that with the only once collagenase type IV digestion (20.0%) and little higher than thrice collagenase type IV digestion (37.5%). The FAP expression of CAFs was quite different from normal fibroblasts (NFs). The fibroblasts isolated by the innovation are with high purity and being in wonderful condition and display the features of CAFs.