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ABSTRACT: Mutations in key tumor suppressor genes such as tumor protein 53 (TP53) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) are the main genetic alterations in cancers. TP53 mutations have been found in most patients with non-small cell lung cancer (NSCLC), whereas PTEN mutations are rarely found in lung cancer, though most NSCLCs lack PTEN protein synthesis. However, the signaling involved in radio- and chemotherapy of NSCLC with wild-type PTEN and nonfunctional p53 is not clearly understood.
In this study, we established a xenograft tumor model with H358 NSCLC cells expressing wild-type PTEN, but nonfunctional p53. Protein expression and phosphorylation of PTEN and its downstream signal molecules in NSCLC tissues were detected by Western blot.
We demonstrated that radiation and paclitaxel alone inhibited tumor growth, but a combined therapy of radiation and paclitaxel was more effective in inhibiting NSCLC tumor growth. Interestingly, both radiation and paclitaxel significantly increased PTEN protein expression and phosphorylation. Further identification of the affected PTEN downstream molecules showed that Akt phosphorylation at Ser(473) and Thr(308) residues was significantly decreased, whereas Bax and cleaved caspase-3 levels were significantly increased in tumor tissues treated with both radiation and paclitaxel. The combined treatment was more effective than either treatment alone in regulating the studied molecules. We also found that paclitaxel, but not radiation, inhibited phosphoinositide 3-kinase (PI3K) activity.
Our study suggested that a PTEN-PI3K-Akt-Bax signaling cascade is involved in the therapeutic effect of combined radiation/paclitaxel treatment in NSCLC without p53 expression. Our study also suggested that PTEN is an ideal target in tumors with wild-type PTEN and a lack of functional p53.
Cancer Biotherapy & Radiopharmaceuticals 04/2012; 27(4):227-33. · 1.44 Impact Factor
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ABSTRACT: This study aimed to compare clinical and pathologic data for selected patients with congenital heart disease (CHD) and severe pulmonary hypertension (PH) treated with a diagnostic-treatment-and-repair strategy and to compare results for patients with pulmonary vascular disease (PVD) with simple left-to-right shunt CHD with patients with transposition of the great arteries (TGA) and ventricular septal defect (VSD).
Group I comprised 38 patients with simple left-to-right shunt CHD and severe PH; group II included 11 older patients with TGA with VSD and severe PH; and group III comprised 6 autopsy cases of individuals with a normal circulation. The nature of the pulmonary arteries was determined by the Heath-Edwards classification system. All specimens were quantitatively analyzed.
Group I showed 31 patients with a change to grade I, 3 patients were grade II, 3 patients were grade III, and only 1 patient was grade IV. Group II showed 7 patients with a change to grade I, 2 patients were grade II, 1 patient was grade III, and only 1 patient was grade IV. The media wall thickness percentage (%MT), the media wall area percentage (%MS), and arteriole density were significantly higher in groups I and II than in group III. %MS was significantly higher in group II than in group I; no significant differences in %MT and arteriole density could be found between groups I and II.
The PVD in these selected patients with CHD and severe PH who were cared for with a diagnostic-treatment-and-repair strategy is generally reversible, and the changes in PVD in the patients with TGA and VSD were similar to those in the patients with simple left-to-right shunt CHD.
Heart Surgery Forum 04/2012; 15(2):E97-102. · 0.63 Impact Factor
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ABSTRACT: The goal of the study was to evaluate the quality of life of children after the older corrective arterial switch operation (ASO) by means of the Pediatric Quality of Life Inventory (PedsQL), version 4.0.
The records of 86 patients who had complete transposition of the great arteries plus a nonrestrictive ventricular septal defect, or a Taussig-Bing anomaly, and severe pulmonary arterial hypertension, and who underwent a corrective ASO at an older age (>6 months) between May 2000 and October 2008 were reviewed retrospectively. Eighty survivors were followed up, and the health-related quality of life of the survivors was evaluated with the PedsQL, version 4.0.
There were 6 hospital deaths. The mean (SD) follow-up interval was 3.5 ± 2.3 years, and the mean age at last visit was 7.0 ± 1.2 years. Two late deaths occurred, and 8 patients were lost to follow-up. Patients who underwent a corrective ASO at an older age showed acceptable scores for all scales, and they were all comparable with those of a healthy population.
Our data suggest that the quality of life of children who undergo a corrective ASO at an older age (>6 months) is acceptable, compared with that of healthy children in China.
Heart Surgery Forum 04/2012; 15(2):E103-7. · 0.63 Impact Factor
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ABSTRACT: The role of the hinge region in the unwinding and cleavage of type I collagen by interstitial collagenase (MMP-1) has been studied at 37 °C and pH 7.3. The collagenolytic processing by MMP-1 displays a very similar overall rate for both chains of collagen I, even though the affinity is higher for the α-1 chain and the cleavage rate is faster for the α-2 chain. MMP-1 binding to collagen I brings about a significant unwinding of the triple-helical arrangement only after the first cleavage step of the α-1 and α-2 chains. The proteolytic processing by wild-type MMP-1 on a synthetic substrate and collagen I has been compared with that observed for site-directed mutants obtained either by truncating the hinge region (∆255-272) or by individually replacing the conserved amino acids Val268, Gly272, and Lys277 of the hinge region with residues observed for the corresponding position in stromelysin-1 (MMP-3), a noncollagenolytic metalloproteinase. The ∆256-272 mutant has no collagenolytic activity, clearly demonstrating the crucial role of this region for the enzymatic processing of collagen I. However, among various mutants investigated, only Gly272Asp shows a dramatically reduced enzymatic activity both on the synthetic substrate and on collagen I. This effect, however, is clearly related to the substituting residue, since substitution of Ala or Asn for Gly272 does not have any effect on the kinetic properties of MMP-1. These data suggest that the substrate specificity of MMP-1 is dictated by the reciprocal structural relationships between the catalytic domain and the carboxy-terminal domain through the conformational arrangement of the hinge region.
European Journal of Biochemistry 03/2012; 17(4):663-72. · 3.42 Impact Factor
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ABSTRACT: Loss of PTEN expression is observed in most non-small cell lung cancers (NSCLC). However, the mechanism by which PTEN expression is regulated in NSCLC has not been fully elucidated. In this study, we investigated the role of DNA methyltransferases (Dnmts), microRNA-29b (miR-29b), and anti-miR-29b inhibitor in PTEN promoter methylation and PTEN gene expression in H358 NSCLC cells in vitro and in vivo. PTEN mRNA was measured by RT-PCR. PTEN and Dnmts protein levels were measured by Western blot. miR-29b expression was detected by Northern blot. A xenograft H358 tumor mouse model was established by subcutaneously inoculating H358 cells into the right hind limbs of nude mice. We found that radiation induced cell apoptosis and hypomethylation in PTEN promoter, PTEN and miR-29b expression, and downregulation of Dnmt1, 3a and 3b expression in H358 tumor cells. The effect of radiation on gene expression and apoptosis was blocked by anti-miR-29b inhibitor. In the xenograft H358 tumor model, anti-miR-29b inhibitor reversed radiation-induced tumor growth delay, PTEN reexpression and downregulation of Dnmts expression. Our study suggested that miR-29b is an upstream molecule of PTEN. miR-29b regulates PTEN gene expression through downregulating Dnmts expression and subsequently induces hypomethylation in PTEN promoter. Targeting therapy could be established in NSCLC by upregulating miR-29b expression.
Biochemical and Biophysical Research Communications 02/2012; 418(3):547-52. · 2.48 Impact Factor
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ABSTRACT: Recently, advanced therapies for pulmonary arterial hypertension have become available, and have been effective in reducing pulmonary vascular resistance and symptoms in patients with Eisenmenger syndrome, previously thought to be inoperable. This review summarizes the current knowledge on the pathophysiology and treatment of Eisenmenger syndrome. The recent introduction of targeted therapies in pulmonary arterial hypertension has led to a renewed insight in the pathophysiology and treatment of Eisenmenger syndrome. Patients with Eisenmenger syndrome using a diagnostic-treatment-and-repair strategy are amenable to surgery after successful treatment with advanced therapy. With continued improvements in the diagnosis, preoperative management, refinement of surgical techniques and intra- and postoperative management strategies, the patients with Eisenmenger syndrome selected using a diagnostic-treatment-and-repair strategy are operable with safety and efficacy in the current era with advanced pulmonary arterial hypertension therapy. Future directions of Eisenmenger syndrome may be the combination of reversal of pulmonary vascular remodeling and correction.
Respiratory care 02/2012; 57(9):1488-95. · 2.01 Impact Factor
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01/2012; , ISBN: 978-953-307-472-6
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ABSTRACT: A method coupling high-performance liquid chromatography (HPLC) with diode-array detector (DAD) and electrospray ionization mass spectrometry (ESI) was established for the separation and characterization of flavonoids in Sophora flavescens Ait. Based on the chromatographic separation of most flavonoids present in S. flavescens Ait., a total of 24 flavonoids were identified. Fourteen compounds were unambiguously identified comparing experimental data for retention time (t(R)), UV and MS spectra with those of the authentic compounds: 3',7-dihydroxy-4'-methoxy-isoflavone (13), trifolirhizin (14), kurarinol (18), formononetin (19), 7,4'-dihydroxy-5-methoxy-8-(gamma,gamma-dimethylallyl)-flavanone (22), maackiain (21), isoxanthohumol (23), kuraridine (26), kuraridinol (27), sophoraflavanone G (30), xanthohumol (31), isokurarinone (33), kurarinone (35) and kushenol D (38), and additional 10 compounds were tentatively identified as kushenol O (10), trifolirhizin-6''-malonate (15), sophoraisoflavanone A (20), norkurarinol/kosamol Q (24), kushenol I/N (25), kushenol C (28), 2'-methoxykurarinone (29), kosamol R (32), kushecarpin A (34) and kushenol A (37) by comparing experimental data for UV and MS spectra with those of literature. Furthermore, fragmentation pathways in positive ions mode of 24 flavonoid compounds of types of flavanone, flavanonol, flavonol, chalcone, isoflavone, isoflavanone and ptercocarpane were summarized. Some common features, such as CH(3)., H(2)O, CO, CO(2), C(3)O(2) and C(2)H(2)O losses, together with Retro-Diels-Alder fragmentations were observed in the prenylated flavonoids in S. flavescens Ait. The loss of the lanandulyl chain was their characteristic fragmentation, which might help deducing the structure of unknown flavonoid compounds. The present study provided an approach to rapidly characterize bioactive constituents in S. flavescens Ait.
Journal of Pharmaceutical and Biomedical Analysis 10/2007; 44(5):1019-28. · 2.97 Impact Factor
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ABSTRACT: A high-performance liquid chromatography coupled with photodiode array detection and electrospray ionization tandem mass spectrometry
(HPLC-DAD-ESI-MS2) method was firstly developed for a chemical fingerprint analysis of Scutellariae Radix and rapid identification of major
compounds in the fingerprints. The experimental data for chromatography were used for hierarchical clustering analysis and
similarity calculation, and those for UV and MS spectra were applied for identifying characteristic peaks. Twenty samples
including S. baicalensis Georgi., S. viscidula Bge. and S. amoena C. H. Wright were classified into three groups. By comparing the UV and MS spectra data with those of the authentic standards
and literature, 20 main peaks in the fingerprints were identified for the first time. The developed fingerprint assay was
specific and could be readily utilized for comprehensive evaluation of Scutellariae Radix.
Chromatographia 01/2007; 66(1):13-20. · 1.20 Impact Factor
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ABSTRACT: Both in terms of number of participating users and in traffic volume, KaZaA is one of the most important applications in the Internet today. Nevertheless, because KaZaA is proprietary and uses encryption, little is understood about KaZaA's overlay structure and dynamics, its messaging protocol, and its index manage-ment. We have built two measurement apparatus -the KaZaA Sniffing Platform and the KaZaA Probing Tool -to unravel many of the mysteries behind KaZaA. We deploy the apparatus to study KaZaA's overlay structure and dynamics, its neighbor selection, its use of dynamic port numbers to circumvent firewalls, and its index management. Although this study does not fully solve the KaZaA puzzle, it nevertheless leads to a coherent description of KaZaA and its overlay. Further-more, we leverage the measurement results to set forth a number of key principles for the design of a successful unstructured P2P overlay. The measurement results and resulting design principles in this paper should be useful for future architects of P2P overlay networks as well as for engineers managing ISPs.
10/2004;
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ABSTRACT: The unwarping of curved document images is a crucial problem for camera-based document analysis since most of current OCR techniques can not handle distortion due to perspective and warping. In previous work we have shown how to recover the page shape from a single image using an iterative procedure without camera calibration, and using the shape information to restore a frontal view of a flat doc-ument. In this paper we report our recent progress using a global optimization method to do shape estimation. Experi-mental results show a clear improvement over our previous method.
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ABSTRACT: In this paper, we present a method for composing document mosaics from camera-captured images. We decompose the complexity of solving the 8-dof transformation between image pairs into two problems, that is, rectification and registration. This is achievable under a key assumption that sufficient text content forms orthogonal texture flows on the document surface. First, perspective distortion and rotation are removed from images using the texture flow information. Next, the translation and scaling are resolved by a Hough transform-like voting method. In the image composition part, our contribution is a sharpness based selection process which composes a seamless and blur free mosaic for text content. Experiments show that our approach can produce an accurate, sharp, and high resolution mosaic of a full document page from small image patches captured by a camera with various zooms and poses.
Computer Vision and Image Understanding.
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ABSTRACT: Both in terms of number of participating users and in traffic volume, FastTrack is one of the most important applications in the Internet today. Nevertheless, because FastTrack is proprietary and uses encryption, little is understood about FastTrack’s overlay structure and dynamics, its messaging protocol, and its index management. We have built two measurement apparatus—the FastTrack Sniffing Platform and the FastTrack Probing Tool—to unravel many of the mysteries behind FastTrack. We deploy the apparatus to study FastTrack’s overlay structure and dynamics, its neighbor selection, its use of dynamic port numbers to circumvent firewalls, and its index management. Although this study does not fully solve the FastTrack puzzle, it nevertheless leads to a coherent description of FastTrack and its overlay. Furthermore, we leverage the measurement results to set forth a number of key principles for the design of a successful unstructured P2P overlay. The measurement results and resulting design principles in this paper should be useful for future architects of P2P overlay networks as well as for engineers managing ISPs.
Computer Networks.
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ABSTRACT: To further understand the relationship between vegetation succession and soil fertility within farming-plantation ecotone in Ziwuling Mountains of the Loess Plateau, nine kinds of widely distributed communities at different succession stages were selected, and the effects of vegetation succession on soil fertility were studied through the methods of comparing two hierarchical clustering (similarity index: ) and other multivariate analysis. The results showed that: (i) the similarity in clustering pattern of nine communities which classified by plant species and soil nutrients respectively showed a trend of overall plant-soil 0–10 cm>overall plant-soil 10–20 cm>overall plant-soil 20–40 cm, and for the top soil, it showed a trend of grass-soil 0–10 cm>shrub-soil 0–10 cm>tree-soil 0–10 cm; (ii) soil fertility increased during the succession process from abandoned land to forest community, and the soil fertility of forest community showed an increased order of coniferous forest →mixed forest →broadleaf forest; (iii) during the process of vegetation succession, the variation of topsoil fertility was higher than that of the subsurface soil (coefficient of variation: CV0–10 cm > CV10–20 cm > CV20–40 cm), and when the succession developed into the stages of shrub and forest communities, the top soil fertility had been improved significantly; and (iv) for the subsurface soil of the communities at the advanced succession stages, the soil fertility also increased to some extent. Our results suggested that the method of comparing two hierarchical clustering reflected the similarity level of different cluster patterns, therefore, it was helpful to study the relationship between vegetation succession and soil fertility. There was a corresponding relationship between the change process of soil fertility from the top soil to subsurface soil and the process of vegetation succession from the early stages to the advanced stage. The differentiations of soil fertility in vertical space and horizontal space were both caused by vegetation succession, which was significant for both the shrub and forest communities. The improved level of forest soil fertility was related to forest vegetation types and the improved fertility level of broad-leaved forest-soil community was higher than that of the coniferous forest soil. In the practice on soil fertility ecological restoration of the loess plateau, it is important to carry out reasonably artificial forestation so as to enhance the restoration and improvement of soil fertility.
Agricultural Sciences in China.
