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1.  Metabolic regulation of cancer cell side population by glucose through activation of the Akt pathway 
Cell Death and Differentiation  2013;21(1):124-135.
Side population (SP) cells within tumors are a small fraction of cancer cells with stem-like properties that can be identified by flow cytometry analysis based on their high ability to export certain compounds such as Hoechst 33342 and chemotherapeutic agents. The existence of stem-like SP cells in tumors is considered as a key factor contributing to drug resistance, and presents a major challenge in cancer treatment. Although it has been recognized for some time that tumor tissue niches may significantly affect cancer stem cells (CSCs), the role of key nutrients such as glucose in the microenvironment in affecting stem-like cancer cells and their metabolism largely remains elusive. Here we report that SP cells isolated from human cancer cells exhibit higher glycolytic activity compared to non-SP cells. Glucose in the culture environment exerts a profound effect on SP cells as evidenced by its ability to induce a significant increase in the percentage of SP cells in the overall cancer cell population, and glucose starvation causes a rapid depletion of SP cells. Mechanistically, glucose upregulates the SP fraction through ATP-mediated suppression of AMPK and activation of the Akt pathway, leading to elevated expression of the ATP-dependent efflux pump ABCG2. Importantly, inhibition of glycolysis by 3-BrOP significantly reduces SP cells in vitro and impairs their ability to form tumors in vivo. Our data suggest that glucose is an essential regulator of SP cells mediated by the Akt pathway, and targeting glycolysis may eliminate the drug-resistant SP cells with potentially significant benefits in cancer treatment.
doi:10.1038/cdd.2013.131
PMCID: PMC3857620  PMID: 24096870
glucose; cancer cell side population; glycolysis; Akt; ABCG2
2.  Metastatic Malignant Ectomesenchymoma Initially Presenting as a Pelvic Mass: Report of a Case and Review of Literature 
Case Reports in Pediatrics  2014;2014:792925.
Pediatric soft tissue sarcomas account for approximately 10% of all pediatric malignancies. Malignant ectomesenchymoma is rare biphasic sarcomas consisting of both mesenchymal and neuroectodermal elements. Approximately 64 cases have been reported in the literature and are believed to arise from pluripotent embryologic migratory neural crest cells. We report a 4-year-old boy who initially presented with a pelvic mass and inguinal lymphadenopathy at 6 months of age. Inguinal lymph node biopsy revealed a distinct biphasic tumor with microscopic and immunophenotypic characteristics diagnostic for both alveolar rhabdomyosarcoma and poorly differentiated neuroblastoma. The patient received national protocol chemotherapy against rhabdomyosarcoma with good response and presented with a cerebellar mass 21 months later. The metastatic tumor revealed sheets of primitive tumor cells and diagnostic areas of rhabdomyosarcoma and neuroblastoma were identified only by immunohistochemistry. Cytogenetic analysis of metastatic tumor demonstrated complex karyotype with multiple chromosomal deletions and duplications. The patient received national protocol chemotherapy against neuroblastoma and adjuvant radiotherapy after surgical resection of the cerebellar tumor with good response. He is currently off from any treatment for 18 months with no evidence of tumor recurrence or metastasis.
doi:10.1155/2014/792925
PMCID: PMC4227373  PMID: 25405050
3.  Association of vitamin B6, vitamin B12 and methionine with risk of breast cancer: a dose–response meta-analysis 
British Journal of Cancer  2013;109(7):1926-1944.
Background:
Epidemiological studies evaluating the association of vitamin B6, vitamin B12 and methionine with breast cancer risk have produced inconsistent results.
Methods:
Pertinent studies were identified by a search in PubMed and Web of Knowledge. Random-effect model was used. Dose–response relationship was assessed by restricted cubic spline.
Results:
The combined relative risk (95% confidence interval) of breast cancer for the highest vs lowest category of serum pyridoxal 5′-phosphate (PLP, active form of vitamin B6) levels and dietary methionine intake was 0.80 (0.66–0.98, P=0.03) and 0.94 (0.89–0.99, P=0.03), respectively, and the associations of breast cancer with higher serum PLP levels and dietary methionine intake were significant among post-menopausal women, but not among pre-menopausal women. The inverse association between breast cancer risk and dietary vitamin B6 intake, serum vitamin B12 levels and dietary vitamin B12 intake was not significant overall. Linear dose–response relationship was found, and the risk of breast cancer decreased by 23% (P<0.00) for every 100 pmol ml−1 increment in PLP levels and 4% (P=0.05) for every 1 g per day increment in dietary methionine intake, respectively.
Conclusion:
Serum PLP levels and methionine intake might be inversely associated with breast cancer risk, especially among postmenopausal women, which need to be confirmed.
doi:10.1038/bjc.2013.438
PMCID: PMC3790153  PMID: 23907430
vitamin B6; vitamin B12; methionine; breast cancer; dose–response meta-analysis
4.  A two-temperature model for selective photothermolysis laser treatment of port wine stains 
Applied thermal engineering  2013;59(1-2):41-51.
Selective photothermolysis is the basic principle for laser treatment of vascular malformations such as port wine stain birthmarks (PWS). During cutaneous laser surgery, blood inside blood vessels is heated due to selective absorption of laser energy, while the surrounding normal tissue is spared. As a result, the blood and the surrounding tissue experience a local thermodynamic non-equilibrium condition. Traditionally, the PWS laser treatment process was simulated by a discrete-blood-vessel model that simplifies blood vessels into parallel cylinders buried in a multi-layer skin model. In this paper, PWS skin is treated as a porous medium made of tissue matrix and blood in the dermis. A two-temperature model is constructed following the local thermal non-equilibrium theory of porous media. Both transient and steady heat conduction problems are solved in a unit cell for the interfacial heat transfer between blood vessels and the surrounding tissue to close the present two-temperature model. The present two-temperature model is validated by good agreement with those from the discrete-blood-vessel model. The characteristics of the present two-temperature model are further illustrated through a comparison with the previously-used homogenous model, in which a local thermodynamic equilibrium assumption between the blood and the surrounding tissue is employed.
doi:10.1016/j.applthermaleng.2013.05.007
PMCID: PMC4123555  PMID: 25110458
laser dermatology; port wine stains; two-temperature model; porous media; local thermal non-equilibrium; Monte-Carlo method
5.  Effect of mode of birth on purine and malondialdehyde in umbilical arterial plasma in normal term newborns 
Objective
To examine the effect of mode of birth on plasma purine and malondialdehyde levels in normal term infants.
Study Design
Umbilical arterial cord blood was obtained immediately after birth from a convenience sample of 119 normal term newborns born by vaginal delivery, with or without oxytocin augmentation or by elective cesarean delivery. Plasma was analyzed for purine and/or malondialdehyde levels. Numeric data were analyzed utilizing independent samples t-test and ordinal data were analyzed using Mann–Whitney test. Correlation coefficients were obtained using Spearman’s ρ.
Result
Uric acid levels were significantly elevated (P<0.001) in neonates undergoing vaginal birth, compared to neonates born by elective cesarean delivery. When the effect of oxytocin and length of labor was analyzed, neonates born to mothers on oxytocin had lower hypoxanthine, significantly lower xanthine (P = 0.05) and higher uric acid levels. In addition, malondialdehyde levels were significantly higher (P<0.006) in neonates born to mothers who received oxytocin compared to neonates born to mothers without oxytocin augmentation. We also found significant correlations between malondialdehyde (MDA) and hypoxanthine (r = −0.465, P< 0.039) and between MDA and xanthine (r = −0.753, P = 0.003) in neonates born via oxytocin-augmented birth. Mode of birth had no statistically significant effect on clinical outcomes, although infants born by elective cesarean had higher incidence of acute respiratory distress and transient tachypnea of the newborn compared to those born vaginally.
Conclusion
Neonates born by elective cesarean had the lowest purine levels in cord blood compared to neonates born vaginally. Oxytocin augmentation is associated with some degree of uterine hyperstimulation which may enhance the ATP degradation pathway resulting in the rapid conversion of hypoxanthine to xanthine and xanthine to uric acid. Significantly higher MDA levels in neonates whose mothers received oxytocin as well as significant correlation between MDA and the purines hypoxanthine and xanthine, suggest free-radical production, most likely due to xanthine oxidase activation. However, despite differences in plasma purine and malondialdehyde levels, no significant differences were seen in neonatal outcome. Further studies are required to fully characterize the effect of mode of birth on purine metabolism and free-radical production.
doi:10.1038/jp.2008.29
PMCID: PMC4158434  PMID: 18368062
mode of birth; purines; MDA
6.  Inhibiting the intrinsic pathway of coagulation with a FXII-targeting RNA Aptamer 
Journal of thrombosis and haemostasis : JTH  2013;11(7):10.1111/jth.12302.
Background
Exposure of the plasma protein factor XII to an anionic surface generates activated factor XII that not only triggers the intrinsic pathway of blood coagulation through the activatio of factor XI, but also mediates various vascular responses through activation of the plasma contact system. While deficiencies of factor XII are not associated with excessive bleeding, thrombosis models in factor deficient animals have suggested that this protein contributes to stable thrombus formation. Therefore, factor XII has emerged as an attractive therapeutic target to treat or prevent pathological thrombosis formation without increasing the risk for hemorrhage.
Objectives
Utilizing an in vitro directed evolution and chemical biology approach, we sought to isolate a nuclease resistant RNA aptamer that binds specifically to factor XII and directly inhibits factor XII coagulant function.
Methods and Results
Herein, we describe the isolation and characterization of a high affinity RNA aptamer targeting factor XII/XIIa that dose dependently prolongs fibrin clot formation and thrombin generation in clinical coagulation assays. This aptamer functions as a potent anticoagulant by inhibiting the autoactivation of factor XII, as well as inhibiting intrinsic pathway activation (factor XI activation). However, the aptamer does not affect the factor XIIa-mediated activation of the proinflammatory kallikrein-kinin system (plasma kallikrein activation).
Conclusions
We have generated a specific and potent factor XII/XIIa aptamer anticoagulant that offers targeted inhibition of discrete macromolecular interactions involved in the activation of the intrinsic pathway of blood coagulation.
doi:10.1111/jth.12302
PMCID: PMC3816843  PMID: 23692437
RNA Aptamers; Factor XII; Factor XIIa; Anticoagulant Agents; Blood Coagulation
7.  MicroRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis 
British Journal of Cancer  2013;108(3):653-661.
Background:
MicroRNA (miRNA, miR)-18a is a member of the miR-17–92 cluster, an important locus that is markedly overexpressed in several cancers and associated with cancer development and progression. However, the mechanism of action of the miR-17–92 cluster and its individual miRNAs are largely unknown.
Methods and Results:
In this study, we investigated the expression of the miR-17–92 cluster by in situ hybridisation (ISH) assay and copy-number analysis in gastric tissue microarray (TMA) specimens. We determined that miR-18a was present at higher levels than the other five miRNAs in the cluster. In addition, we identified Protein Inhibitor of Activated Signal Transducer and Activator of Transcription 3 (PIAS3) as a direct target of miR-18a in gastric cancer. miR-18a level was positively correlated with levels of Survivin, Bcl-xL, and c-Myc, which are downstream transcriptional targets of Signal Transducer and Activator of Transcription 3 (STAT3). STAT3-induced transcription can be negatively regulated by PIAS3; consistent with this, PIAS3 level was negatively correlated with levels of Survivin, Bcl-xL, and c-Myc.
Conclusion:
Our findings indicate that miR-18a acts as an oncogene and plays a role in gastric adenocarcinogenesis, at least in part by negatively regulating PIAS3 and thereby modulating expression of STAT3 target genes.
doi:10.1038/bjc.2012.587
PMCID: PMC3593546  PMID: 23322197
gastric adenocarcinoma; microRNA-18a; PIAS3; STAT3; Survivin; Bcl-xL; c-Myc
8.  NK Cells Inhibit T-bet-deficient, Autoreactive Th17 Cells 
The differentiation and maintenance of Th17 cells require a unique cytokine milieu and activation of lineage-specific transcription factors. This process appears to be antagonized by the transcription factor T-bet, which controls the differentiation of Th1 cells. Considering that T-bet-deficient (T-bet−/−) mice are largely devoid of natural killer (NK) cells due to a defect in the terminal maturation of these cells, and because NK cells can influence the differentiation of T helper cells, we investigated whether the absence of NK cells in T-bet-deficient mice contributes to the augmentation of autoreactive Th17 cell responses. We show that the loss of T-bet renders the transcription factors Rorc and STAT3 highly responsive to activation by stimuli provided by NK cells. Furthermore, reconstitution of T-bet−/− mice with wild-type NK cells inhibited the development of autoreactive Th17 cells through NK cell-derived production of IFN-γ. These results identify NK cells as critical regulators in the development of autoreactive Th17 cells and Th17-mediated pathology.
doi:10.1111/j.1365-3083.2012.02773.x
PMCID: PMC3600979  PMID: 22928727
10.  ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3β in the signal network 
Feng, L | Zhang, D | Fan, C | Ma, C | Yang, W | Meng, Y | Wu, W | Guan, S | Jiang, B | Yang, M | Liu, X | Guo, D
Cell Death & Disease  2013;4(7):e715-.
HeLa cells treated with celastrol, a natural compound with inhibitive effect on proteasome, exhibited increase in apoptotic rate and characteristics of apoptosis. To clarify the signal network activated by celastrol to induce apoptosis, both the direct target proteins and undirect target proteins of celastrol were searched in the present study. Proteasome catalytic subunit β1 was predicted by computational analysis to be a possible direct target of celastrol and confirmed by checking direct effect of celastrol on the activity of recombinant human proteasome subunit β1 in vitro. Undirect target-related proteins of celastrol were searched using proteomic studies including two-dimensional electrophoresis (2-DE) analysis and iTRAQ-based LC-MS analysis. Possible target-related proteins of celastrol such as endoplasmic reticulum protein 29 (ERP29) and mitochondrial import receptor Tom22 (TOM22) were found by 2-DE analysis of total cellular protein expression profiles. Further study showed that celastrol induced ER stress and ER stress inhibitor could ameliorate cell death induced by celastrol. Celastrol induced translocation of Bax into the mitochondria, which might be related to the upregulation of BH-3-only proteins such as BIM and the increase in the expression level of TOM22. To further search possible target-related proteins of celastrol in ER and ER-related fractions, iTRAQ-based LC-MS method was use to analyze protein expression profiles of ER/microsomal vesicles-riched fraction of cells with or without celastrol treatment. Based on possible target-related proteins found in both 2-DE analysis and iTRAQ-based LC-MS analysis, protein–protein interaction (PPI) network was established using bioinformatic analysis. The important role of glycogen synthase kinase-3β (GSK3β) in the signal cascades of celastrol was suggested. Pretreatment of LiCL, an inhibitor of GSK3β, could significantly ameliorate apoptosis induced by celastrol. On the basis of the results of the present study, possible signal network of celastrol activated by celastrol leading to apoptosis was predicted.
doi:10.1038/cddis.2013.222
PMCID: PMC3730400  PMID: 23846217
celastrol; apoptosis; endothelium reticulum; proteomics; bioinformatics
11.  Feasibility study on retinal vascular bypass surgery in isolated arterially perfused caprine eye model 
Chen, Y | Wu, W | Zhang, X | Fan, W | Shen, L
Eye  2011;25(11):1499-1503.
Purpose
To investigate the feasibility of bypassing occluded segments of retinal venous main vessels in isolated, arterially perfused caprine eyes via the closed-sky vitrectomy approach using keratoprosthesis.
Methods
Isolated caprine eyes were used in this study. For each eye, the retinal vessel was perfused by Krebs solution via ophthalmic artery, and pars plana vitrectomy was performed using temporary keratoprosthesis. All retinal micro-vascular maneuvers were performed in a closed-sky eyeball. The main retinal vein was blocked by endodiathermy at the site of the vessel's first branching. Two openings, several millimeters apart, were created by vascular punctures in both the main vein and its branch vein wall straddling the induced occluded segment. Catheterization was achieved using a flexible polyimide tube, with each end inserted into the vessel wall opening. A sealed connection between the vessel and the tube was obtained by endodiathermy. Bypass of the occluded retinal vein segment was thus achieved, and the patency of this vascular bypass was confirmed by intravascular staining.
Results
Puncturing, catheterization, and endodiathermy were viable by closed-sky approach using keratoprosthesis. Bypassing of the occluded retinal main vein segment was accomplished with the combination of these maneuvers. Good results were obtained in 23 of 38 (60%) caprine eyes.
Conclusions
This study demonstrated that bypassing the occluded segment of retinal main vein can be successfully performed in a closed-sky eyeball model of isolated, arterially perfused caprine eye. This early work indicated that the more advanced retinal vascular bypass surgery in in vivo eye may be feasible in the future.
doi:10.1038/eye.2011.197
PMCID: PMC3213656  PMID: 21921946
retinal vein occlusion; retinal vein bypass surgery; isolated arterially perfused caprine eye; closed-sky eyeball; keratoprosthesis
12.  Effects of Merogel coverage on wound healing and ostial patency in endonasal endoscopic dacryocystorhinostomy for primary chronic dacryocystitis 
Wu, W | Cannon, P S | Yan, W | Tu, Y | Selva, D | Qu, J
Eye  2011;25(6):746-753.
Purpose
To investigate the effects of Merogel coverage on ostial patency in endonasal endoscopic dacryocystorhinostomy (EES-DCR) for primary chronic dacryocystitis (PCD).
Methods
In all, 260 patients with unilateral PCD were randomized into two groups: the Merogel group and the control group. All patients underwent EES-DCR. The Merogel group received Merogel covering the wound 1–2 mm around the ostium and the control group received no treatment. Patients were followed up for 9 months. The mucosal epithelialization of the wound, the proliferation of fibrosis tissue, and the success rate of ostial patency were compared.
Results
Our study included 112 patients in the Merogel group and 115 patients in the control group. At the 2-week review, intact mucosal epithelium lined the ostia in 96 Merogel patients compared with 80 control patients (ITT analysis: χ 2=4.502, P=0.034). At the 9-month review, scars were present in 18 patients in the Merogel group compared with 39 patients in the control group (ITT analysis: χ 2=9.909, P=0.002, ITT analysis). No differences were observed in the granulation formation between the two groups. The success rate of ostial patency reached 94.6% (106/112) in the Merogel group compared with 80% (92/115) in the control group (ITT analysis: χ 2=4.151, P=0.042).
Conclusion
Merogel coverage may enhance the success rate of EES-DCR for PCD by promoting mucosal epithelial healing and preventing excessive scarring.
doi:10.1038/eye.2011.44
PMCID: PMC3178118  PMID: 21394118
endonasal endoscopic dacryocystorhinostomy; hyaluronan; ostial patency; mucosa epithelialization; primary chronic dacryocystitis
13.  MicroRNA dysregulation in colorectal cancer: a clinical perspective 
British Journal of Cancer  2011;104(6):893-898.
Recent researches have shed light on the biological importance of microRNAs (miRNAs) in colorectal cancer (CRC) genesis, progression and response to treatments. The potential utility of miRNAs in the preclinical stage have been explored and investigated. In this review, we explored the literature and reviewed the cutting edge progress in the discovery of noninvasive plasma and faecal miRNAs for CRC early diagnosis, as well as their measurability and predictability. We also discussed the utility of miRNAs as novel prognostic and predictive markers, and their association with CRC clinical phenotypes including recurrence, metastasis and therapeutic outcomes. Finally, we summarised miRNA-related single-nucleotide polymorphisms and their potential influence on sporadic CRC susceptibility and therapeutic response. In conclusion, the use of miRNAs as biomarker for CRC is still in its infancy and need further characterisation and evaluation.
doi:10.1038/bjc.2011.57
PMCID: PMC3065287  PMID: 21364594
miRNA; colorectal cancer; diagnostic marker; prognostic marker; single-nucleotide polymorphisms
14.  Very Small Embryonic-Like Stem Cells in adult tissues – potential implications for aging 
Recently our group identified in murine bone marrow (BM) and human cord blood (CB), a rare population of Very Small Embryonic-Like (VSEL) stem cells. We hypothesize that these cells are deposited during embryonic development in BM as a mobile pool of circulating pluripotent stem cells (PSC) that play a pivotal role in postnatal tissue turnover both of non-hematopoietic and hematopoietic tissues. During in vitro co-cultures with murine myoblastic C2C12 cells, VSELs form spheres that contain primitive stem cells. Cells isolated from these spheres may give rise to cells from all three germ layers when plated in tissue specific media. The number of murine VSELs and their ability to form spheres decreases with the age and is reduced in short-living murine strains. Thus, developmental deposition of VSELs in adult tissues may potentially play an underappreciated role in regulating the rejuvenation of senescent organs. We envision that the regenerative potential of these cells could be harnessed to decelerate aging processes.
doi:10.1016/j.mad.2008.02.003
PMCID: PMC3164811  PMID: 18377952
Oct-4; Nanog; SSEA; CXCR4; VSELs; embryonic stem cells
15.  Brain tissue sodium concentration in multiple sclerosis: a sodium imaging study at 3 tesla 
Brain  2010;133(3):847-857.
Neuro-axonal degeneration occurs progressively from the onset of multiple sclerosis and is thought to be a significant cause of increasing clinical disability. Several histopathological studies of multiple sclerosis and experimental autoimmune encephalomyelitis have shown that the accumulation of sodium in axons can promote reverse action of the sodium/calcium exchanger that, in turn, leads to a lethal overload in intra-axonal calcium. We hypothesized that sodium magnetic resonance imaging would provide an indicator of cellular and metabolic integrity and ion homeostasis in patients with multiple sclerosis. Using a three-dimensional radial gradient-echo sequence with short echo time, we performed sodium magnetic resonance imaging at 3 T in 17 patients with relapsing–remitting multiple sclerosis and in 13 normal subjects. The absolute total tissue sodium concentration was measured in lesions and in several areas of normal-appearing white and grey matter in patients, and corresponding areas of white and grey matter in controls. A mixed model analysis of covariance was performed to compare regional tissue sodium concentration levels in patients and controls. Spearman correlations were used to determine the association of regional tissue sodium concentration levels in T2- and T1-weighted lesions with measures of normalized whole brain and grey and white matter volumes, and with expanded disability status scale scores. In patients, tissue sodium concentration levels were found to be elevated in acute and chronic lesions compared to areas of normal-appearing white matter (P < 0.0001). The tissue sodium concentration levels in areas of normal-appearing white matter were significantly higher than those in corresponding white matter regions in healthy controls (P < 0.0001). The tissue sodium concentration value averaged over lesions and over regions of normal-appearing white and grey matter was positively associated with T2-weighted (P ≤ 0.001 for all) and T1-weighted (P ≤ 0.006 for all) lesion volumes. In patients, only the tissue sodium concentration value averaged over regions of normal-appearing grey matter was negatively associated with the normalized grey matter volume (P = 0.0009). Finally, the expanded disability status scale score showed a mild, positive association with the mean tissue sodium concentration value in chronic lesions (P = 0.002), in regions of normal-appearing white matter (P = 0.004) and normal-appearing grey matter (P = 0.002). This study shows the feasibility of using in vivo sodium magnetic resonance imaging at 3 T in patients with multiple sclerosis. Our findings suggest that the abnormal values of the tissue sodium concentration in patients with relapsing–remitting multiple sclerosis might reflect changes in cellular composition of the lesions and/or changes in cellular and metabolic integrity. Sodium magnetic resonance imaging has the potential to provide insight into the pathophysiological mechanisms of tissue injury when correlation with histopathology becomes available.
doi:10.1093/brain/awp334
PMCID: PMC2842511  PMID: 20110245
sodium imaging; multiple sclerosis; tissue sodium concentration; brain atrophy; clinical disability
16.  A study on the influence of breathing phases in intensity-modulated radiotherapy of lung tumours using four-dimensional CT 
The British Journal of Radiology  2010;83(987):252-256.
During gated intensity-modulated radiotherapy (IMRT) treatment for patients with inoperable non-small cell lung cancer (NSCLC), the end-expiration (EE) phase of respiratory is more stable, whereas end-inspiration (EI) spares more normal lung tissue. This study compared the relative plan quality based on dosimetric and biological indices of the planning target volume (PTV) and organs at risk (OARs) between EI and EE in gated IMRT. 16 Stage I NSCLC patients, who were scanned by four-dimensional CT, were recruited and re-planned. An IMRT plan of a prescription dose of 60 Gy per respiratory phase was computed using the iPlan treatment planning system. The heart, spinal cord, both lungs and PTV were outlined. The tumour control probability for the PTV and normal tissue complication probability for all OARs in the EE and EI phases were nearly the same; only the normal tissue complication probability of the heart in EE was slightly lower. Conversely, the conformation number of the PTV, V20 of the left lung, V30 of both lungs, Dmax of the heart and spinal cord, V10 of the heart and D5% of the spinal cord were better in EE, whereas Dmean of the PTV, V20 of the right lung and maximum doses of both lungs were better in EI. No differences reached statistical significance (p<0.05) except Dmax of the spinal cord (p _ 0.033). Overall, there was no expected clinical impact between EI and EE in the study. However, based on the practicality factor, EI is recommended for patients who can perform breath-hold; otherwise, EE is recommended.
doi:10.1259/bjr/33094251
PMCID: PMC3473553  PMID: 19723769
17.  Synthesis and Magnetic Properties of Maghemite (γ-Fe2O3) Short-Nanotubes 
Nanoscale Research Letters  2010;5(9):1474-1479.
We report a rational synthesis of maghemite (γ-Fe2O3) short-nanotubes (SNTs) by a convenient hydrothermal method and subsequent annealing process. The structure, shape, and magnetic properties of the SNTs were investigated. Room-temperature and low-temperature magnetic measurements show that the as-fabricated γ-Fe2O3 SNTs are ferromagnetic, and its coercivity is nonzero when the temperature above blocking temperature (TB). The hysteresis loop was operated to show that the magnetic properties of γ-Fe2O3 SNTs are strongly influenced by the morphology of the crystal. The unique magnetic behaviors were interpreted by the competition of the demagnetization energy of quasi-one-dimensional nanostructures and the magnetocrystalline anisotropy energy of particles in SNTs.
doi:10.1007/s11671-010-9664-4
PMCID: PMC2920399  PMID: 20730115
Short-nanotubes; γ-Fe2O3; Magnetic properties
18.  Synthesis and Magnetic Properties of Maghemite (γ-Fe2O3) Short-Nanotubes 
Nanoscale Research Letters  2010;5(9):1474-1479.
We report a rational synthesis of maghemite (γ-Fe2O3) short-nanotubes (SNTs) by a convenient hydrothermal method and subsequent annealing process. The structure, shape, and magnetic properties of the SNTs were investigated. Room-temperature and low-temperature magnetic measurements show that the as-fabricated γ-Fe2O3 SNTs are ferromagnetic, and its coercivity is nonzero when the temperature above blocking temperature (TB). The hysteresis loop was operated to show that the magnetic properties of γ-Fe2O3 SNTs are strongly influenced by the morphology of the crystal. The unique magnetic behaviors were interpreted by the competition of the demagnetization energy of quasi-one-dimensional nanostructures and the magnetocrystalline anisotropy energy of particles in SNTs.
doi:10.1007/s11671-010-9664-4
PMCID: PMC2920399  PMID: 20730115
Short-nanotubes; γ-Fe2O3; Magnetic properties
19.  Transcatheter closure of patent ductus arteriosus with severe pulmonary arterial hypertension in adults 
Yan, C | Zhao, S | Jiang, S | Xu, Z | Huang, L | Zheng, H | Ling, J | Wang, C | Wu, W | Hu, H | Zhang, G | Ye, Z | Wang, H
Heart  2006;93(4):514-518.
Background
Surgical closure of patent ductus arteriosus (PDA) with severe pulmonary arterial hypertension in adults carries higher risk than in children.
Objectives
To investigate the application of self‐expandable occluders for transcatheter closure of PDA associated with severe pulmonary arterial hypertension in adults, and the assessment of immediate and short‐term results.
Methods
29 adult patients (6 men, 23 women) underwent attempted transcatheter closure of PDA at a mean (standard deviation (SD)) age of 31.1 (11.4) years (range 18–58 years) and a mean (SD) weight of 54.1 (7.1) kg (range 42–71 kg). On the basis of haemodynamic and clinical data obtained before and after trial occlusion, the final duct occlusion was determined and carried out. Radiographs of the chest, electrocardiograms and echocardiograms were used for follow‐up evaluation of the treatment within 1 day, 1 month and 3–6 months after successful closure.
Results
20 of the 29 patients had successful occlusion (group 1), and 9 patients failed (named group 2). In group 1, in which occlusion was successful, mean (SD) pulmonary arterial pressures decreased markedly after trial occlusion: 78 (19.3) mm Hg (range 50–125 mm Hg) before occlusion and 41 (13.8) mm Hg (range 23–77 mm Hg) after occlusion. Systemic arterial oxygen saturation was found to be >90% in 19 patients and <90% in the remaining patient before inhalation of oxygen, and >95% during inhalation of oxygen or after occlusion in all 20 patients. In group 2, the occlusion was not successful, because in two patients the device was not available; another two patients showed worsening of symptoms. The other five patients showed increased pulmonary arterial pressures after trial closure; their mean (SD) pulmonary arterial pressures increased by 10.3 (6) mm Hg (4–16 mm Hg) after trial occlusion, and systemic arterial oxygen saturation was 85.5% (2.6%) (range 82.6–88%) before inhalation of oxygen and 94.7% (1.7%) (range 90.7–99.1%) during inhalation of oxygen. In group 1, the dimensions of the left atrium, left ventricle and pulmonary artery increased considerably in 3–6‐months of follow‐up compared with those of preocclusion.
Conclusions
Transcatheter closure is an effective treatment for adults with PDA associated with reversible severe pulmonary arterial hypertension. Further research is needed for the evaluation of long‐term results.
doi:10.1136/hrt.2006.091215
PMCID: PMC1861497  PMID: 16954130
20.  Self-Organized Ni Nanocrystal Embedded in BaTiO3 Epitaxial Film 
Nanoscale Research Letters  2010;5(5):834-838.
Ni nanocrystals (NCs) were embedded in BaTiO3 epitaxial films using the laser molecular beam epitaxy. The processes involving the self-organization of Ni NCs and the epitaxial growth of BaTiO3 were discussed. With the in situ monitoring of reflection high-energy electron diffraction, the nanocomposite films were engineered controllably by the fine alternation of the self-organization of Ni NCs and the epitaxial growth of BaTiO3. The transmission electron microscopy and the X-ray diffraction characterization confirmed that the composite film consists of the Ni NCs layers alternating with the (001)/(100)-oriented epitaxial BaTiO3 separation layers.
doi:10.1007/s11671-010-9570-9
PMCID: PMC2894189  PMID: 20672067
Laser molecular beam epitaxy; Nanocomposite film; Reflection high-energy electron diffraction; Self-organization; Epitaxial growth
21.  Role for PADI6 and the CPLs in Ribosomal Storage in Oocytes and Translation in the Early Embryo 
Development (Cambridge, England)  2008;135(15):2627-2636.
The mechanisms mediating the establishment of totipotency during the egg-to-embryo transition in mammals remain poorly understood. The cytoplasmic lattices (CPLs), a structure unique to mammalian oocytes and preimplantation embryos, have long been predicted to function as a storage form for the maternal contribution of ribosomes and mRNA to the early embryo. Here, we demonstrate that oocyte- and embryo-restricted peptidylarginine deiminase 6 (PADI6) is required for incorporation of ribosomal components into the oocyte CPLs. Next, we show that the abundance and localization of ribosomal components is dramatically affected in PADI6-/- two-cell embryos and that de novo protein synthesis is also disregulated in these embryos. Finally, we demonstrate that embryonic genome activation (EGA) is defective in PADI6 -/- two-cell embryos. These results suggest that, in mammals, ribosomal components are stored in the oocyte CPLs and are required for protein translation during early development.
doi:10.1242/dev.016329
PMCID: PMC2708103  PMID: 18599511
22.  Overexpression/amplification of HER-2/neu is uncommon in hepatocellular carcinoma 
Journal of Clinical Pathology  2005;58(5):500-503.
Background: Hepatocellular carcinoma (HCC) is one of the most prevalent fatal cancers in the world. Despite advances in early diagnosis and improvements in surgical techniques, the survival of patients with HCC even after resection is poor because of the high incidence of recurrences. Therefore, the identification of prognostic factors may be helpful in the development of new treatment protocols.
Aims: To investigate HER-2/neu status in HCC by immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), and to explore the possibility of using trastuzumab in the treatment of HCC.
Methods: Eight hundred and sixty eight surgical samples from patients with primary HCC were examined for their HER-2/neu status. IHC for HER-2/neu was performed with the HercepTest kit; FISH analysis was performed with the PathVysion HER-2 DNA probe kit. The correlations between HER-2/neu overexpression and clinicopathological characteristics were analysed statistically.
Results: HER-2/neu overexpression was detected in 21 (2.42%) of the 868 primary HCCs. Only one specimen showed HER-2/neu gene amplification by FISH. No significant associations were found between HER-2/neu overexpression and the clinicopathological parameters.
Conclusions: There is a low frequency of HER-2/neu overexpression/amplification in HCC. There appears to be no role for HER-2/neu as a prognostic marker and no benefit of anti-HER-2/neu trastuzumab treatment in patients with HCC.
doi:10.1136/jcp.2004.023556
PMCID: PMC1770655  PMID: 15858121
HER-2/neu; hepatocellular carcinoma; fluorescence in situ hybridisation; immunohistochemistry
23.  Embryonic Expression and Extracellular Secretion of Xenopus Slit 
Neuroscience  2000;96(1):231-236.
The slit genes have recently been found to encode proteins with a conserved chemorepulsive activity for axons in invertebrates and vertebrates. We have determined the expression pattern of a slit gene in Xenopus embryos. In the neural tube, slit is expressed at the ventral and dorsal midlines, and the motor neurons. slit is also expressed in a changing pattern in the retina. The full-length Xenopus Slit protein is secreted extracellularly, whereas its receptor Roundabout can not be secreted. Using a myc-tagged secreted Slit protein, we confirmed the binding of Slit to Roundabout expressed on the cell surface.
These results confirm Slit–Roundabout interactions and the biochemical properties of Slit and Roundabout proteins, and further support the idea that Slit may guide axon projections in multiple regions of the embryo.
PMCID: PMC2072876  PMID: 10683427
Slit; Roundabout; olfactory bulb; axon guidance; chemorepulsion
24.  Characterization of Low-Pathogenic H5 Subtype Influenza Viruses from Eurasia: Implications for the Origin of Highly Pathogenic H5N1 Viruses▿  
Journal of Virology  2007;81(14):7529-7539.
Highly pathogenic avian influenza (HPAI) H5N1 viruses are now endemic in many Asian countries, resulting in repeated outbreaks in poultry and increased cases of human infection. The immediate precursor of these HPAI viruses is believed to be A/goose/Guangdong/1/96 (Gs/GD)-like H5N1 HPAI viruses first detected in Guangdong, China, in 1996. From 2000 onwards, many novel reassortant H5N1 influenza viruses or genotypes have emerged in southern China. However, precursors of the Gs/GD-like viruses and their subsequent reassortants have not been fully determined. Here we characterize low-pathogenic avian influenza (LPAI) H5 subtype viruses isolated from poultry and migratory birds in southern China and Europe from the 1970s to the 2000s. Phylogenetic analyses revealed that Gs/GD-like virus was likely derived from an LPAI H5 virus in migratory birds. However, its variants arose from multiple reassortments between Gs/GD-like virus and viruses from migratory birds or with those Eurasian viruses isolated in the 1970s. It is of note that unlike HPAI H5N1 viruses, those recent LPAI H5 viruses have not become established in aquatic or terrestrial poultry. Phylogenetic analyses revealed the dynamic nature of the influenza virus gene pool in Eurasia with repeated transmissions between the eastern and western extremities of the continent. The data also show reassortment between influenza viruses from domestic and migratory birds in this region that has contributed to the expanded diversity of the influenza virus gene pool among poultry in Eurasia.
doi:10.1128/JVI.00327-07
PMCID: PMC1933357  PMID: 17507485
25.  Role of VraSR in Antibiotic Resistance and Antibiotic-Induced Stress Response in Staphylococcus aureus 
Antimicrobial Agents and Chemotherapy  2006;50(10):3424-3434.
Exposure of Staphylococcus aureus to cell wall inhibitors induces massive overexpression of a number of genes, provided that the VraSR two-component sensory regulatory system is intact. Inactivation of vraS blocks this transcriptional response and also causes a drastic reduction in the levels of resistance to beta-lactam antibiotics and vancomycin. We used an experimental system in which the essential cell wall synthesis gene of S. aureus, pbpB, was put under the control of an isopropyl-β-d-thiogalactopyranoside-inducible promoter in order to induce reversible perturbations in cell wall synthesis without the use of any cell wall-active inhibitor. Changes in the level of transcription of pbpB were rapidly followed by parallel changes in the vraSR signal, and the abundance of the pbpB transcript was precisely mirrored by the abundance of the transcripts of vraSR and some additional genes that belong to the VraSR regulon. Beta-lactam resistance in S. aureus appears to involve a complex stress response in which VraSR performs the critical role of a sentinel system capable of sensing the perturbation of cell wall synthesis and allowing mobilization of genes that are essential for the generation of a highly resistant phenotype. One of the sites in cell wall synthesis “sensed” by the VraSR system appears to be a step catalyzed by PBP 2.
doi:10.1128/AAC.00356-06
PMCID: PMC1610096  PMID: 17005825

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