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991.
Chuanzheng Sun Qiuli Li Zedong Hu Jiehua He Chao Li Guojun Li Xiaofeng Tao Ankui Yang 《PloS one》2013,8(11)
Background
Anaplastic thyroid carcinoma (ATC), a highly aggressive malignancy, has a poor prognosis, and the consensus on the most effective treatment is needed.Methods
Clinical data from all ATC patients treated in our institution over a 30-year period (between May 1980 and May 2010) were analyzed retrospectively with regard to mortality and survival rates (Kaplan–Meier). Multivariate analysis was performed using a Cox proportional hazards model.Results
Sixty cases were analyzed. The overall 1- and 3-year survival rates were 35.0% and 22.9%, respectively. Univariate analysis showed that the best prognosis was seen in patients younger than 55 years, those without distant metastases, those with white blood cell (WBC) counts < 10.0 × 109/L or blood platelet (PLT) counts < 300.0 × 109/L at presentation, those who did not receive chemotherapy, and those who received radiotherapy doses ≥ 40 Gy or underwent surgery plus postoperative radiotherapy. According to multivariate analysis, the WBC count at first presentation and the type of therapeutic regimen independently influenced survival.Conclusions
We found that the elevated peripheral PLT count may be an adverse prognostic factor of ATC patients. The prognosis for ATC is especially poor for patients with distant metastasis, a WBC count ≥ 10.0×109/L, a PLT count ≥ 300.0 × 109/L, or age ≥ 55 years. WBC count at presentation and surgery with or without postoperative radiotherapy independently influenced the prognosis. Intensive treatment combining surgery with postoperative radiotherapy is recommended for ATC patients with stage IVA/B disease. 相似文献992.
Activated persulfate oxidation technologies based on sulfate radicals were first evaluated for defluorination of aqueous perfluorooctanesulfonate (PFOS). The influences of catalytic method, time, pH and K2S2O8 amounts on PFOS defluorination were investigated. The intermediate products during PFOS defluorination were detected by using LC/MS/MS. The results showed that the S2O8
2− had weak effect on the defluorination of PFOS, while the PFOS was oxidatively defluorinated by sulfate radicals in water. The defluorination efficiency of PFOS under various treatment was followed the order: HT (hydrothermal)/K2S2O8 > UV (ultraviolet)/K2S2O8 > Fe2+/K2S2O8 > US (ultrasound)/K2S2O8. Low pH was favorable for the PFOS defluorination with sulfate radicals. Increase in the amount of S2O8
2− had positive effect on PFOS defluorination. However, further increase in amounts of S2O8
2− caused insignificant improvement in PFOS defluorination due to elimination of sulfate radicals under high concentration of S2O8
2−. CF3(CF2)nCOOH (n = 0–6) were detected as intermediates during PFOS defluorination. Sulfate radicals oxidation and hydrolysis were the main mechanisms involved in defluorination process of PFOS. 相似文献
993.
Shufeng Li Xiaofeng Huang Dapeng Zhang Qilai Huang Guoshun Pei Lixiang Wang Wenhui Jiang Qingang Hu Renxiang Tan Zi-Chun Hua 《PloS one》2013,8(11)
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase critically involved in cancer metastasis. We found an elevation of FAK expression in highly metastatic melanoma B16F10 cells compared with its less metastatic partner B16F1 cells. Down-regulation of the FAK expression by either small interfering RNA or dominant negative FAK (FAK Related Non-Kinase, FRNK) inhibited the B16F10 cell migration in vitro and invasiveness in vivo. The mechanism by which FAK activity is up-regulated in highly metastatic cells remains unclear. In this study, we reported for the first time that one of the Est family proteins, PEA3, is able to transactivate FAK expression through binding to the promoter region of FAK. We identified a PEA3-binding site between nucleotides −170 and +43 in the FAK promoter that was critical for the responsiveness to PEA3. A stronger affinity of PEA3 to this region contributed to the elevation of FAK expression in B16F10 cells. Both in vitro and in vivo knockdown of PEA3 gene successfully mimicked the cell migration and invasiveness as that induced by FAK down-regulation. The activation of the well-known upstream of PEA3, such as epidermal growth factor, JNK, and ERK can also induce FAK expression. Furthermore, in the metastatic human clinic tumor specimens from the patients with human primary oral squamous cell carcinoma, we observed a strong positive correlation among PEA3, FAK, and carcinoma metastasis. Taking together, we hypothesized that PEA3 might play an essential role in the activation of the FAK gene during tumor metastasis. 相似文献
994.
Yan Xu Wan-jun Guo Qiang Wang Gongga Lanzi Ouzhu Luobu Xiao-hong Ma Ying-cheng Wang Puo Zhen Wei Deng Xiang Liu Basang Zhuoma Xie-he Liu Tao Li Xun Hu 《PloS one》2013,8(11)
Studies of linkage and association in various ethnic populations have revealed many predisposing genes of multiple neurotransmitter systems for alcohol use disorders (AUD). However, evidence often is contradictory regarding the contribution of most candidate genes to the susceptibility of AUD. We, therefore, performed a case-control study to investigate the possible associations of genes selected from multiple neurotransmitter systems with AUD in a homogeneous Tibetan community population in China. AUD cases (N = 281) with an alcohol use disorder identification test (AUDIT) score ≥10, as well as healthy controls (N = 277) with an AUDIT score ≤5, were recruited. All participants were genotyped for 366 single nucleotide polymorphisms (SNPs) of 34 genes selected from those involved in neurotransmitter systems. Association analyses were performed using PLINK version 1.07 software. Allelic analyses before adjustment for multiple tests showed that 15 polymorphisms within seven genes were associated with AUD (p<0.05). After adjustment for the number of SNPs genotyped within each gene, only the association of a single marker (rs10044881) in HTR4 remained statistically significant. Haplotype analysis for two SNPs in HTR4 (rs17777298 and rs10044881) showed that the haplotype AG was significantly associated with the protective effect for AUD. In conclusion, the present study discovered that the HTR4 gene may play a marked role in the pathogenesis of AUD. In addition, this Tibetan population sample marginally replicated previous evidence regarding the associations of six genes in AUD. 相似文献
995.
Zhigang Ren Guangying Cui Haifeng Lu Xinhua Chen Jianwen Jiang Hui Liu Yong He Songming Ding Zhenhua Hu Weilin Wang Shusen Zheng 《PloS one》2013,8(10)
Background
Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT).Methods
The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis.Principal Findings
Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum.Conclusion
Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”. 相似文献996.
Previously, we have documented that isolated autophagosomes from tumor cells could efficiently cross-prime tumor-reactive naïve T cells and mediate tumor regression in preclinical mouse models. However, the effect of tumor-derived autophagosomes, here we refer as to DRibbles, on B cells has not been studied so far. At present study, we found that DRibbles generated from a murine hepatoma cell line Hep1-6, induced B-cell activation after intravenous injection into mice. B-cell populations were significantly expanded and the production of Hep1-6 tumor-specific antibodies was successfully induced. Moreover, in vitro studies showed that DRibbles could induce more efficient B-cell proliferation and activation, antibody production, and cytokine secretion than whole tumor cell lysates. Notably, we found that B-cell activation required proteins but not DNA in the DRibbles. We further showed that B cells could capture DRibbles and present antigens in the DRibbles to directly induce T cell activation. Furthermore, we found that B-cell activation, antibody production, cytokine secretion and antigen cross-presentation were TLR2-MyD88 pathway dependent. Taken together, the present studies demonstrated that tumor-derived autophagosomes (DRibbles) efficiently induced B cells activation, antibody production, cytokine secretion and antigen cross-presentation mainly depending on their protein component via TLR2/MyD88 dependent manner. 相似文献
997.
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998.
Willi Halfter Joseph Candiello Haiyu Hu Peng Zhang Emanuel Schreiber Manimalha Balasubramani 《Cell Adhesion & Migration》2013,7(1):64-71
Basement membranes (BMs) evolved together with the first metazoan species approximately 500 million years ago. Main functions of BMs are stabilizing epithelial cell layers and connecting different types of tissues to functional, multicellular organisms. Mutations of BM proteins from worms to humans are either embryonic lethal or result in severe diseases, including muscular dystrophy, blindness, deafness, kidney defects, cardio-vascular abnormalities or retinal and cortical malformations. In vivo-derived BMs are difficult to come by; they are very thin and sticky and, therefore, difficult to handle and probe. In addition, BMs are difficult to solubilize complicating their biochemical analysis. For these reasons, most of our knowledge of BM biology is based on studies of the BM-like extracellular matrix (ECM) of mouse yolk sac tumors or from studies of the lens capsule, an unusually thick BM. Recently, isolation procedures for a variety of BMs have been described, and new techniques have been developed to directly analyze the protein compositions, the biomechanical properties and the biological functions of BMs. New findings show that native BMs consist of approximately 20 proteins. BMs are four times thicker than previously recorded, and proteoglycans are mainly responsible to determine the thickness of BMs by binding large quantities of water to the matrix. The mechanical stiffness of BMs is similar to that of articular cartilage. In mice with mutation of BM proteins, the stiffness of BMs is often reduced. As a consequence, these BMs rupture due to mechanical instability explaining many of the pathological phenotypes. Finally, the morphology and protein composition of human BMs changes with age, thus BMs are dynamic in their structure, composition and biomechanical properties. 相似文献
999.
Patrick Giraudoux Francis Raoul David Pleydell Tiaoying Li Xiuming Han Jiamin Qiu Yan Xie Hu Wang Akira Ito Philip S. Craig 《PLoS neglected tropical diseases》2013,7(3)
Background
Human alveolar echinococcocosis (AE) is a highly pathogenic zoonotic disease caused by the larval stage of the cestode E. multilocularis. Its life-cycle includes more than 40 species of small mammal intermediate hosts. Therefore, host biodiversity losses could be expected to alter transmission. Climate may also have possible impacts on E. multilocularis egg survival. We examined the distribution of human AE across two spatial scales, (i) for continental China and (ii) over the eastern edge of the Tibetan plateau. We tested the hypotheses that human disease distribution can be explained by either the biodiversity of small mammal intermediate host species, or by environmental factors such as climate or landscape characteristics.Methodology/findings
The distributions of 274 small mammal species were mapped to 967 point locations on a grid covering continental China. Land cover, elevation, monthly rainfall and temperature were mapped using remotely sensed imagery and compared to the distribution of human AE disease at continental scale and over the eastern Tibetan plateau. Infection status of 17,589 people screened by abdominal ultrasound in 2002–2008 in 94 villages of Tibetan areas of western Sichuan and Qinghai provinces was analyzed using generalized additive mixed models and related to epidemiological and environmental covariates. We found that human AE was not directly correlated with small mammal reservoir host species richness, but rather was spatially correlated with landscape features and climate which could confirm and predict human disease hotspots over a 200,000 km2 region.Conclusions/Significance
E. multilocularis transmission and resultant human disease risk was better predicted from landscape features that could support increases of small mammal host species prone to population outbreaks, rather than host species richness. We anticipate that our study may be a starting point for further research wherein landscape management could be used to predict human disease risk and for controlling this zoonotic helminthic. 相似文献1000.
Joe Fu-Jiou Lo Yong Wang Zidong Li Zhengtuo Zhao Di Hu David T. Eddington Jose Oberholzer 《Journal of visualized experiments : JoVE》2013,(81)
Simultaneous oxygenation and monitoring of glucose stimulus-secretion coupling factors in a single technique is critical for modeling pathophysiological states of islet hypoxia, especially in transplant environments. Standard hypoxic chamber techniques cannot modulate both stimulations at the same time nor provide real-time monitoring of glucose stimulus-secretion coupling factors. To address these difficulties, we applied a multilayered microfluidic technique to integrate both aqueous and gas phase modulations via a diffusion membrane. This creates a stimulation sandwich around the microscaled islets within the transparent polydimethylsiloxane (PDMS) device, enabling monitoring of the aforementioned coupling factors via fluorescence microscopy. Additionally, the gas input is controlled by a pair of microdispensers, providing quantitative, sub-minute modulations of oxygen between 0-21%. This intermittent hypoxia is applied to investigate a new phenomenon of islet preconditioning. Moreover, armed with multimodal microscopy, we were able to look at detailed calcium and KATP channel dynamics during these hypoxic events. We envision microfluidic hypoxia, especially this simultaneous dual phase technique, as a valuable tool in studying islets as well as many ex vivo tissues. 相似文献