It is well known that Oct4 and Sox2 play an important role in the maintenance of embryonic stem cell pluripotency. These transcription factors bind to regulatory regions within hundreds of target genes to control their expression. Zfp206 is a recently characterized transcription factor that has a role in maintaining stem cell pluripotency. We have demonstrated here that Zfp206 is a direct downstream target of Oct4 and Sox2. Two composite sox-oct binding sites have been identified within the first intron of Zfp206. We have demonstrated binding of Oct4 and Sox2 to this region. In addition, we have shown that Oct4 or Sox2 alone can activate transcription via one of these sox-oct elements, although the presence of both Oct4 and Sox2 gave rise to a synergistic effect. These studies extend our understanding of the transcriptional network that operates to regulate the differentiation potential of embryonic stem cells. Embryonic stem cells (ESCs)2 are derived from the inner cell mass of the blastocyst and exhibit both pluripotency and selfrenewing capabilities. For proper developmental outcome, ESCs must tightly regulate their differentiation status, and through continuing study, the molecular basis of that regulation process is beginning to emerge. Systematic, genome-wide interrogations have identified hundreds of genes, including several transcription factors, which have expression patterns tightly correlated with ES cell differentiation (1-6). Two key transcription factors, Oct4 and Sox2, have been identified that are crucial for maintenance of the pluripotent state of ESCs (7,8). ESCs lose the capacity to maintain pluripotency upon knockdown of expression of these transcription factors by RNA interference (9, 10). Gene knock-out studies confirm the importance of Oct4 and Sox2 for early embryonic development. It has been demonstrated by chromatin immunoprecipitation studies that Oct4 and Sox2 bind to a few thousand regulatory sites in the ES cell genome (11,12). It is likely that many of these target genes play a role in modulating ES cell differentiation. Indeed, the transcription factor Nanog, an established regulator of pluripotency, is transcriptionally regulated directly by Oct4 and Sox2 (13).Zfp206 is a transcription factor that is highly expressed in mouse and human ESCs and down-regulated upon differentiation (3, 14). Zfp206 contains a SCAN domain and 14 zinc-finger domains, which suggests that it may be a transcription factor that binds DNA directly. Zfp206 is expressed in the inner cell mass but not in trophectoderm, suggesting that it may play a role in establishing cell fate decisions regarding embryonic versus extraembryonic tissue (15). There is wide temporal and spatial distribution of RNA and protein in the early embryos, indicating that Zfp206 may regulate multiple cell fate decisions (14). Recent data have demonstrated that overexpression of Zfp206 promotes the formation of undifferentiated mouse ESC colonies in vitro (14). We have obtained similar results and further found that overexpression of Zf...
BackgroundThe effectiveness of immunotherapy for high-grade glioma (HGG) patients remains controversial. To evaluate the therapeutic efficacy of dendritic cells (DCs) alone in the treatment of HGG, we performed a systematic review and meta-analysis in terms of patient survival with relevant published clinical studies.Materials and methodsA total of 409 patients, including historical cohorts, nonrandomized and randomized controls with HGG, were selected for the meta-analysis.ResultsThe treatment of HGG with DCs was associated with a significantly improved one-year survival (OS) (p<0.001) and 1.5-, 2-, 3-, 4-, and 5-year OS (p<0.001) compared with the non-DC group. A meta-analysis of the patient outcome data revealed that DC immunotherapy has a significant influence on progression-free survival (PFS) in HGG patients, who showed significantly improved 1-,1.5-, 2-, 3- and 4-year PFS (p<0.001). The analysis of Karnofsky performance status (KPS) demonstrated no favorable results for DC cell therapy arm (p = 0.23).The percentages of CD3+CD8+ and CD3+CD4+ T cells and CD16+ lymphocyte subset were not significantly increased in the DC group compared with the baseline levels observed before treatment (p>0.05), whereas CD56+ lymphocyte subset were significantly increased after DC treatment (p = 0.0001). Furthermore, the levels of IFN-γ in the peripheral blood of HGG patients, which reflect the immune function of the patients, were significantly increased after DC immunotherapy (p<0.001).ConclusionsThus, our meta-analysis showed that DC immunotherapy markedly prolongs survival rates and progression-free time, enhances immune function, and improves the efficacy of the treatment of HGG patients.
Aim: Peripheral arterial disease (PAD), particularly critical limb ischemia (CLI), is a severe cause of amputation and mortality. More than 50% of diabetic patients with CLI die within four to five years. The development of novel stem cell therapies may bring new hope to these patients. We aimed to assess the efficacy of autologous bone marrow cell therapy for treating CLI using a meta-analysis. Methods: We searched the literature in PubMed, the Cochrane Central Registry of Controlled Trials, the Elsevier database and EBSCO for trials of autologous cell therapy in patients with severe PAD published before October 30, 2013. We chose objective clinical endpoints to assess the efficacy of therapy in the meta-analysis, including changes in the ankle-brachial index (ABI), transcutaneous oxygen tension (TcO2), pain scale (0-10 scale) and amputation-free survival (AFS). Results: Thirty-one articles reporting clinical trials involving a total of 1,214 patients treated with bone marrow stem cell-based therapy were collected for the meta-analysis, in which the randomized controlled trials (RCTs) and other trials (non-RCTs) were classified into two groups. Regarding the efficacy of stem cell therapy, the ABI showed significant increases (P<0.05) at 12 , 24 and 48 weeks after therapy in the non-RCT and RCT groups, but not after four to eight weeks in the non-RCT group. The TcO2 values also increased in the RCT group at four to eight weeks after therapy and 24 weeks after therapy (P<0.001) and in the non-RCT group at four to eight weeks after therapy (P = 0.01), although no significant increases were observed in the RCT group at 12 weeks after therapy or the non-RCT group at 24 weeks after therapy. Meanwhile, pain was significantly reduced (P<0.05) at four to eight weeks and 24 weeks after therapy in both the non-RCT and RCT groups, but not at four to eight weeks or 12 weeks after therapy in the RCT group. In addition, the long-term clinical trials demonstrated that the AFS rate improved after therapy with bone marrow stem cells (one-year AFS, P<0.00001; three-year AFS, P = 0.0003). Conclusions:The present results suggest that autologous bone marrow stem cells have an advantageous therapy effect in PAD patients who are not eligible for revascularization.
The combination of DC-CIK immunotherapy and chemotherapy was superior in prolonging the survival time and enhancing immunological responses.
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