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981.
Anita K. Gandhi Tao Shi Mingyu Li Ulf Jungnelius Alfredo Romano Josep Tabernero Salvatore Siena Peter H. Schafer Rajesh Chopra 《PloS one》2013,8(11)
This study assessed the immunomodulatory effects in previously treated KRAS-mutant metastatic colorectal cancer patients participating in a phase II multicenter, open-label clinical trial receiving lenalidomide alone or lenalidomide plus cetuximab. The main findings show the T cell immunostimulatory properties of lenalidomide as the drug induced a decrease in the percentage CD45RA+ naïve T cells 3-fold while increasing the percentage HLA-DR+ activated T helper cells and percentage total CD45RO+ CD8+ memory T cytotoxic cells, 2.6- and 2.1-fold respectively (p<0.0001). In addition, lenalidomide decreased the percentage of circulating CD19+ B cells 2.6-fold (p<0.0001). Lenalidomide increased a modest, yet significant, 1.4-fold change in the percentage of circulating natural killer cells. Our findings indicate that lenalidomide significantly activates T cells, suggestive of an immunotherapeutic role for this drug in settings of maintenance therapy and tumor immunity. Furthermore, reported for the first time is the effect of lenalidomide in combination with cetuximab on T cell function, including increases in circulating naïve and central memory T cells. In summary, lenalidomide and cetuximab have significant effects on circulating immune cells in patients with colorectal carcinoma.
Trial Registration
ClinicalTrials.gov NCT01032291相似文献982.
Yuhong Zhang Xiaolu Xu Xiaojin Zhou Rumei Chen Peilong Yang Qingchang Meng Kun Meng Huiying Luo Jianhua Yuan Bin Yao Wei Zhang 《PloS one》2013,8(12)
Background
Incorporation of exogenous glucanase into animal feed is common practice to remove glucan, one of the anti-nutritional factors, for efficient nutrition absorption. The acidic endo-β-1,3-1,4-glucanase (Bgl7A) from Bispora sp. MEY-1 has excellent properties and represents a potential enzyme supplement to animal feed.Methodology/Principal Findings
Here we successfully developed a transgenic maize producing a high level of Bgl7AM (codon modified Bgl7A) by constructing a recombinant vector driven by the embryo-specific promoter ZM-leg1A. Southern and Western blot analysis indicated the stable integration and specific expression of the transgene in maize seeds over four generations. The β-glucanase activity of the transgenic maize seeds reached up to 779,800 U/kg, about 236-fold higher than that of non-transgenic maize. The β-glucanase derived from the transgenic maize seeds had an optimal pH of 4.0 and was stable at pH 1.0–8.0, which is in agreement with the normal environment of digestive tract.Conclusion/Significance
Our study offers a transgenic maize line that could be directly used in animal feed without any glucanase production, purification and supplementation, consequently simplifying the feed enzyme processing procedure. 相似文献983.
Gabriel Fung Chen Seng Ng Jingchun Zhang Junyan Shi Jerry Wong Paulina Piesik Lillian Han Fanny Chu Julienne Jagdeo Eric Jan Takashi Fujita Honglin Luo 《PloS one》2013,8(11)
Stress granules (SGs) are dynamic cytosolic aggregates containing messenger ribonucleoproteins and target poly-adenylated (A)-mRNA. A key component of SGs is Ras-GAP SH3 domain binding protein-1 (G3BP1), which in part mediates protein-protein and protein-RNA interactions. SGs are modulated during infection by several viruses, however, the function and significance of this process remains poorly understood. In this study, we investigated the interplay between SGs and Coxsackievirus type B3 (CVB3), a member of the Picornaviridae family. Our studies demonstrated that SGs were formed early during CVB3 infection; however, G3BP1-positive SGs were actively disassembled at 5 hrs post-infection, while poly(A)-positive RNA granules persisted. Furthermore, we confirmed G3BP1 cleavage by 3Cpro at Q325. We also demonstrated that overexpression of G3BP1-SGs negatively impacted viral replication at the RNA, protein, and viral progeny levels. Using electron microscopy techniques, we showed that G3BP1-positive SGs localized near mitochondrial surfaces. Finally, we provided evidence that the C-terminal cleavage product of G3BP1 inhibited SG formation and promoted CVB3 replication. Taken together, we conclude that CVB3 infection selectively targets G3BP1-SGs by cleaving G3BP1 to produce a dominant-negative fragment that further inhibits G3BP1-SG formation and facilitates viral replication. 相似文献
984.
Kai Zhao Wei Li Tingting Huang Xiaomei Luo Gang Chen Yang Zhang Chen Guo Chunxiao Dai Zheng Jin Yan Zhao Hongyu Cui Yunfeng Wang 《PloS one》2013,8(12)
Background
Although the Newcastle disease virus (NDV) inactivated vaccines and attenuated live vaccines have been used to prevent and control Newcastle disease (ND) for years, there are some disadvantages. Recently, newly developed DNA vaccines have the potential to overcome these disadvantages. The low delivery efficiency, however, hindered the application of DNA vaccines for ND in practice.Methodology/Principal Findings
The eukaryotic expression plasmid pVAX1-F (o) DNA that expressed the F gene of NDV encapsulated in PLGA nanoparticles (pFNDV-PLGA-NPs) were prepared by a double emulsion-solvent evaporation method and optimal preparation conditions of the pFNDV-PLGA-NPs were determined. Under the optimal conditions, the pFNDV-PLGA-NPs were produced in good morphology and had high stability with a mean diameter of 433.5±7.5 nm, with encapsulation efficiency of 91.8±0.3% and a Zeta potential of +2.7 mV. Release assay in vitro showed that the fusion gene plasmid DNA could be sustainably released from the pFNDV-PLGA-NPs up to 93.14% of the total amount. Cell transfection test indicated that the vaccine expressed and maintained its bioactivity. Immunization results showed that better immune responses of SPF chickens immunized with the pFNDV-PLGA-NPs were induced compared to the chickens immunized with the DNA vaccine alone. In addition, the safety of mucosal immunity delivery system of the pFNDV-PLGA-NPs was also tested in an in vitro cytotoxicity assay.Conclusions/Significance
The pFNDV-PLGA-NPs could induce stronger cellular, humoral, and mucosal immune responses and reached the sustained release effect. These results laid a foundation for further development of vaccines and drugs in PLGA nanoparticles. 相似文献985.
Preeclampsia is a serious complication of pregnancy, which affects 2–8% of all pregnancies and is one of the leading causes of maternal and perinatal mortality and morbidity worldwide. To better understand the molecular mechanisms involved in pathological development of placenta in preeclampsia, we used high-resolution LC-MS/MS technologies to construct a comparative N-glycoproteomic and phosphoproteomic profiling of human placental plasma membrane in normal and preeclamptic pregnancies. A total of 1027 N-glyco- and 2094 phospho- sites were detected in human placental plasma membrane, and 5 N-glyco- and 38 phospho- proteins, respectively, with differentially expression were definitively identified between control and preeclamptic placental plasma membrane. Further bioinformatics analysis indicated that these differentially expressed proteins correlate with several specific cellular processes occurring during pathological changes of preeclamptic placental plasma membrane. 相似文献
986.
Lin Shi Defeng Wang Winnie C. W. Chu Shangping Liu Yunyun Xiong Yilong Wang Yongjun Wang Lawrence K. S. Wong Vincent C. T. Mok 《PloS one》2013,8(12)
Structural changes after ischemic stroke could affect information communication extensively in the brain network. It is likely that the defects in the white matter (WM) network play a key role in information interchange. In this study, we used graph theoretical analysis to examine potential organization alteration in the WM network architecture derived from diffusion tensor images from subjects with no dementia and experienced stroke in the past 5.4–14.8 months (N = 47, Mini-Mental Screening Examination, MMSE range 18–30), compared with a normal control group with 44 age and gender-matched healthy volunteers (MMSE range 26–30). Region-wise connectivity was derived from fiber connection density of 90 different cortical and subcortical parcellations across the whole brain. Both normal controls and patients with chronic stroke exhibited efficient small-world properties in their WM structural networks. Compared with normal controls, topological efficiency was basically unaltered in the patients with chronic stroke, as reflected by unchanged local and global clustering coefficient, characteristic path length, and regional efficiency. No significant difference in hub distribution was found between normal control and patient groups. Patients with chronic stroke, however, were found to have reduced betweenness centrality and predominantly located in the orbitofrontal cortex, whereas increased betweenness centrality and vulnerability were observed in parietal-occipital cortex. The National Institutes of Health Stroke Scale (NIHSS) score of patient is correlated with the betweenness centrality of right pallidum and local clustering coefficient of left superior occipital gyrus. Our findings suggest that patients with chronic stroke still exhibit efficient small-world organization and unaltered topological efficiency, with altered topology at orbitofrontal cortex and parietal-occipital cortex in the overall structural network. Findings from this study could help in understanding the mechanism of cognitive impairment and functional compensation occurred in patients with chronic stroke. 相似文献
987.
Ying Zhang Jing Hu Hong-Jun Lu Jian-Ping Li Ning Wang Wei-Wei Li Yong-Chun Zhou Jun-Yue Liu Sheng-Jun Wang Jing Wang Xia Li Wan-Ling Ma Li-Chun Wei Mei Shi 《PloS one》2013,8(11)
Purpose
To determine the optimal standardized uptake value (SUV) of 18F-fluorodeoxyglucose (18F-FDG) for positron emission tomography (PET) imaging, at which the PET-defined gross tumor volume (GTVPET) best matches with the pathological volume (GTVPATH) in the cervical cancer.Materials and Methods
Ten patients with the cervical cancer who underwent surgery were enrolled in this study. The excised specimens were processed for whole-mount serial sections and H-E staining. The tumor borders were outlined in sections under a microscope, histopathological images were scanned and the GTVPATH calculated. The GTVPET was delineated automatically by using various percentages relative to the maximal SUV and absolute SUV. The optimal threshold SUV was further obtained as the value at which the GTVPET best matched with the GTVPATH.Results
An average of 85±10% shrinkage of tissue was observed after the formalin fixation. The GTVPATH was 13.38±2.80 cm3 on average. The optimal threshold on percentile SUV and absolute SUV were 40.50%±3.16% and 7.45±1.10, respectively. The correlation analysis showed that the optimal percentile SUV threshold was inversely correlated with GTVPATH (p<0.05) and tumor diameter (p<0.05). The absolute SUV was also positively correlated with SUVmax (p<0.05).Conclusion
The pathological volume could provide the more accurate tumor volume. The optimal SUV of FDG for PET imaging by use of GTVPATH as standard for cervical cancer target volume delineation was thus determined in this study, and more cases are being evaluated to substantiate this conclusion. 相似文献988.
989.
Bin Sun Xiaofeng Zhang Xianshuo Cheng Yu Zhang Lei Chen Lehua Shi Zhenyu Liu Haihua Qian Mengchao Wu Zhengfeng Yin 《PloS one》2013,8(11)
Hepatic stellate cells (HSCs), a specialized stromal cytotype in the liver, have been demonstrated to actively contribute to hepatocellular carcinoma (HCC) development. However, the previous studies were performed using HSC cell lines, and the prognostic value of intratumoral HSCs (tHSCs) was unclear. Here we isolated tHSCs from fresh human HCC tissues, and analyzed the abilities of tHSCs to promote HCC progression by using in vitro assays for cell viability, migration and invasion as well as epithelial-mesenchymal transition (EMT) phenotype. 252 HCC patients who underwent hepatectomy were enrolled for analysis of tHSCs and E-cadherin expression in tumor tissues, and 55 HCC patients for analysis of tHSCs in tumor tissues and circulating tumor cells (CTCs) in blood. Prognostic factors were then identified. The results showed that coculture of tHSCs with HCC cells had a stronger effect on HCC cell viability, migration and invasion, accompanied with the acquisition of epithelial-mesenchymal transition (EMT) phenotype. In vivo cotransplantation of HCC cells with tHSCs into nude mice more efficiently promoted tumor formation and growth. Icaritin, a known apoptosis inducer of HSCs, was demonstrated to effectively inhibit tHSC proliferation in vitro and tHSC-induced HCC-promoting effects in vivo. Clinical evidence indicated that tHSCs were rich in 45% of the HCC specimens, tHSC-rich subtypes were negatively correlated either with E-cadherin expression in tumor tissues (r = -0.256, p < 0.001) or with preoperative CTCs in blood (r = -0.287, p = 0.033), and were significantly correlated with tumor size (p = 0.027), TNM staging (p = 0.018), and vascular invasion (p = 0.008). Overall and recurrence-free survival rates of tHSC-rich patients were significantly worse than those for tHSC-poor patients. Multivariate analysis revealed tHSC-rich as an independent factor for overall and recurrence-free survival. In conclusion, tHSCs provide a promising prognostic biomarker and a new treatment target for HCC. 相似文献
990.
Xinyu Xu Yun Shi Yun Cai Qingqing Zhang Fan Yang Heng Chen Yong Gu Mei Zhang Liping. Yu Tao Yang 《PloS one》2013,8(11)