bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-519c Suppresses Hypoxia-Inducible Factor-1α Expression and Tumor Angiogenesis
Authors: Cha Shih-Ting , Chen Pai-Sheng , Johansson Gunnar , Chu Chia-Yu , Wang Ming-Yang , Jeng Yung-Ming , Yu Sung-Liang , Chen Jin-Shing , Chang King-Jen , Jee Shiou-Hwa , Tan Ching-Ting , Lin Ming-Tsan , Kuo Min-Liang 
Published: March 2010

Abstract
Hypoxia-inducible factor-1α (HIF-1α) is widely considered to be one of the key regulators of tumor angiogenesis. The upstream regulation is complex and involves several growth factors, cytokines, and hypoxia. Herein, we have identified miR-519c as a hypoxia-independent regulator of HIF-1α, acting through direct binding to the HIF-1α 3′ untranslated region and leading to reduced tumor angiogenesis. Overexpression of miR-519c resulted in a significant decrease of HIF-1α protein levels and reduced the tube formation of human umbilical vein endothelial cells; similarly, antagomir inhibition of miR-519c increased the level of HIF-1α protein and enhanced angiogenic activity, suggesting an important role of miR-519c in HIF-1α–mediated angiogenesis. Consistent with the overexpression of miR-519c in cancer patients with better prognosis, mice injected with miR-519c–overexpressing cells exhibited dramatically reduced HIF-1α levels, followed by suppressed tumor angiogenesis, growth, and metastasis. In addition, we found that hepatocyte growth factor (HGF), a known HIF-1α inducer, reduced the miR-519c levels through an Akt-dependent pathway. This regulation was posttranscriptional and may be mediated by suppression of miR-519c maturation. Taken together, our findings provide the first evidence that miR-519c is a pivotal regulator of tumor angiogenesis and that microenvironmental HGF contributes to regulating miR-519c biogenesis in cancer cells. Cancer Res; 70(7); 2675–85
Cyr61 Mediates Hepatocyte Growth Factor–Dependent Tumor Cell Growth, Migration, and Akt Activation
Authors: Goodwin C. Rory , Lal Bachchu , Zhou Xin , Ho Sandra , Xia Shuli , Taeger Alexandra , Murray Jamie , Laterra John 
Published: March 2010

Abstract
Certain tumor cell responses to the growth factor–inducible early response gene product CCN1/Cyr61 overlap with those induced by the hepatocyte growth factor (HGF)/c-Met signaling pathway. In this study, we investigate if Cyr61 is a downstream effector of HGF/c-Met pathway activation in human glioma cells. A semiquantitative immunohistochemical analysis of 112 human glioma and normal brain specimens showed that levels of tumor-associated Cyr61 protein correlate with tumor grade (P &lt; 0.001) and with c-Met protein expression (r2 = 0.4791, P &lt; 0.0001). Purified HGF rapidly upregulated Cyr61 mRNA (peak at 30 minutes) and protein expression (peak at 2 hours) in HGF−/c-Met+ human glioma cell lines via a transcription- and translation-dependent mechanism. Conversely, HGF/c-Met pathway inhibitors reduced Cyr61 expression in HGF+/c-Met+ human glioma cell lines in vitro and in HGF+/c-Met+ glioma xenografts. Targeting Cyr61 expression with small interfering RNA (siRNA) inhibited HGF-induced cell migration (P &lt; 0.01) and cell growth (P &lt; 0.001) in vitro. The effect of Cyr61 on HGF-induced Akt pathway activation was also examined. Cyr61 siRNA had no effect on the early phase of HGF-induced Akt phosphorylation (Ser473) 30 minutes after stimulation with HGF. Cyr61 siRNA inhibited a second phase of Akt phosphorylation measured 12 hours after cell stimulation with HGF and also inhibited HGF-induced phosphorylation of the Akt target glycogen synthase kinase 3α. We treated preestablished subcutaneous glioma xenografts with Cyr61 siRNA or control siRNA by direct intratumoral delivery. Cyr61 siRNA inhibited Cyr61 expression and glioma xenograft growth by up to 40% in a dose-dependent manner (P &lt; 0.05). These results identify a Cyr61-dependent pathway by which c-Met activation mediates cell growth, cell migration, and long-lasting signaling events in glioma cell lines and possibly astroglial malignancies. Cancer Res; 70(7); 2932–41
A NADPH Oxidase–Dependent Redox Signaling Pathway Mediates the Selective Radiosensitization Effect of Parthenolide in Prostate Cancer Cells
Authors: Sun Yulan , St. Clair Daret K. , Xu Yong , Crooks Peter A. , St. Clair William H. 
Published: March 2010

Abstract
Cancer cells are usually under higher oxidative stress compared with normal cells. We hypothesize that introducing additional reactive oxygen species (ROS) insults or suppressing antioxidant capacity may selectively enhance cancer cell killing by oxidative stress–generating agents through stress overload or stress sensitization, whereas normal cells may be able to maintain redox homeostasis under exogenous ROS by adaptive response. Here, we show that parthenolide, a sesquiterpene lactone, selectively exhibits a radiosensitization effect on prostate cancer PC3 cells but not on normal prostate epithelial PrEC cells. Parthenolide causes oxidative stress in PC3 cells but not in PrEC cells, as determined by the oxidation of the ROS-sensitive probe H2DCFDA and intracellular reduced thiol and disulfide levels. In PC3 but not PrEC cells, parthenolide activates NADPH oxidase, leading to a decrease in the level of reduced thioredoxin, activation of phosphoinositide 3-kinase/Akt, and consequent FOXO3a phosphorylation, which results in the downregulation of FOXO3a targets antioxidant enzyme manganese superoxide dismutase and catalase. Importantly, when combined with radiation, parthenolide further increases ROS levels in PC3 cells whereas it decreases radiation-induced oxidative stress in PrEC cells, possibly by increasing reduced glutathione levels. Together, the results show that parthenolide selectively activates NADPH oxidase and mediates intense oxidative stress in prostate cancer cells by both increasing ROS generation and decreasing antioxidant defense capacity. The results support the concept of exploiting the intrinsic differences in the redox status of cancer cells and normal cells as targets for selective cancer killing. Cancer Res; 70(7); 2880–90
Novel pharmacokinetic behavior of intravenous busulfan in children with thalassemia undergoing hematopoietic stem cell transplantation: a prospective evaluation of pharmacokinetic and pharmacodynamic profile with therapeutic drug monitoring
Authors: Gaziev Javid , Nguyen Laurent , Puozzo Christian , Mozzi Alessia Francesca , Casella Marialuisa , Perrone Donnorso Michela , Gravina Paolo , Sodani Pietro , Marziali Marco , Isgrò Antonella , Simone Maria Domenica , Andreani Marco , Formosa Amanda , Testi Manuela , Federici Giorgio , Bernardini Sergio , Lucarelli Guido 
Published: March 2010

AbstractWe prospectively studied the pharmacokinetics (PK) and clinical outcomes of intravenous busulfan (Bu) in 71 children with preexisting liver damage who underwent hematopoietic stem cell transplantation for thalassemia. Intravenous Bu was administered every 6 hours as part of a conditioning regimen with PK-based dose adjustment to target a conservative area under the concentration-versus-time curve (AUC) range (900-1350 μMol*min). The first-dose Bu clearance (CL) was significantly higher than the subsequent daily CL that remained unchanged in the ensuing days. One-third of patients required dose escalation based on dose 1 AUC, whereas dose reduction was needed in the subsequent days. At doses 5, 9, and 13, 78%, 81%, and 87% of patients, respectively, achieved the target range of AUC. A population PK analysis confirmed that the first-dose CL was 20% higher and that body weight was the most important covariate to explain PK variability. Patients with variant GSTA1*B had a 10% lower Bu CL than wild-type. These results suggest that the disease-specific behavior of intravenous Bu PK should be considered for PK-guided dose adjustment in patients with thalassemia, and the use of a conservative AUC range resulted in low toxicity, good engraftment, and good survival rate.
How does comorbidity affect cost of health care in patients with irritable bowel syndrome? A cohort study in general practice
Authors: Johansson Per A , Farup Per G , Bracco Andrea , Vandvik Per O 
Published: March 2010

Abstract

Background
Irritable bowel syndrome (IBS) is associated with other disorders (comorbidity), reduced quality of life and increased use of health resources. We aimed to explore the impact of comorbidity on cost of health care in patients with IBS in general practice.

Methods
In this cohort study 208 consecutive patients with IBS (Rome II) were recruited. Sociodemographic data, IBS symptoms, and comorbidity (somatic symptoms, organic diseases and psychiatric disorders) were assessed at baseline. Based on a follow up interview after 6-9 months and use of medical records, IBS and non-IBS related health resource use were measured as consultations, hospitalisations, use of medications and alternative health care products and sick leave days. Costs were calculated by national tariffs and reported in Norwegian Kroner (NOK, 1 EURO equals 8 NOK). Multivariate analyses were performed to identify predictors of costs.

Results
A total of 164 patients (mean age 52 years, 69% female, median duration of IBS 17 years) were available at follow up, 143 patients (88%) had consulted their GP of whom 31 (19%) had consulted for IBS. Mean number of sick- leave days for IBS and comorbidity were 1.7 and 16.3 respectively (p < 0.01), costs related to IBS and comorbidity were 954 NOK and 14854 NOK respectively (p < 0.001). Age, organic diseases and somatic symptoms, but not IBS severity, were significant predictors for total costs.

Conclusion
Costs for health resource use among patients with IBS in general practice were largely explained by comorbidity, which generated ten times the costs for IBS.
TRPA1 Modulation of Spontaneous and Mechanically Evoked Firing of Spinal Neurons in Uninjured, Osteoarthritic, and Inflamed Rats
Authors: McGaraughty Steve , Chu Katharine L , Perner Richard J , DiDomenico Stan , Kort Michael E , Kym Philip R 
Published: March 2010

Background: There is growing evidence supporting a role for TRPA1 receptors in the neurotransmission of peripheral mechanical stimulation. In order to enhance understanding of TRPA1 contributions to mechanotransmission, we examined the effects a selective TRPA1 receptor antagonist, A-967079, on spinal neuronal activity following peripheral mechanical stimulation in uninjured, CFA-inflamed, and osteoarthritc (OA) rats. Results: Systemic injection of A-967079 (30 μmol/kg, i.v.) decreased the responses of wide dynamic range (WDR), and nociceptive specific (NS) neurons following noxious pinch stimulation of the ipsilateral hind paw in uninjured and CFA-inflamed rats. Similarly, A-967079 reduced the responses of WDR neurons to high-intensity mechanical stimulation (300 g von Frey hair) of the knee joint in both OA and OA-sham rats. WDR neuronal responses to low-intensity mechanical stimulation (10 g von Frey hair) were also reduced by A-967079 administration to CFA-inflamed rats, but no effect was observed in uninjured rats. Additionally, the spontaneous activity of WDR neurons was decreased after A-967079 injection in CFA-inflamed rats but was unaltered in uninjured, OA, and OA-sham animals. Conclusions: Blockade of TRPA1 receptors disrupts transmission of high-intensity mechanical stimulation to the spinal cord in both uninjured and injured rats indicating that TRPA1 receptors have an important role in noxious mechanosensation in both normal and pathological conditions. TRPA1 receptors also contribute to the transmission of low-intensity mechanical stimulation, and to the modulation of spontaneous WDR firing, but only after an inflammatory injury.
Control of the proliferation of activated CD4+ T cells by connexins
Authors: Oviedo-Orta Ernesto , Perreau Matthieu , Evans W Howard , Potolicchio Ilaria 
Published: March 2010

Abstract
Upon antigen recognition, CD4+ T cells require the expression of Cxs hemichannels to sustain their clonal expansion.
As expression of Cxs in cells of the immune system increases upon cellular activation, we investigated whether Cxs and especially CxHcs play a major role during T cell-mediated responses. In particular, we studied the expression of Cx43Hc following CD4+ T cell stimulation using flow cytometry, real-time PCR, and Western blot analysis. We showed that expression of Cx43 and its phosphorylated isoforms increased in response to the engagement of CD3 and CD28. Cx43Hcs were found to be involved in sustaining proliferation of T cells, as assessed by cell cycle staining, thymidine incorporation assays, and CFSE analysis of cells exposed to mimetic peptide inhibitors of the plasma membrane Cx channels and antibodies generated to an extracellular region of Cx. The reduction of T cell proliferation mediated by Cx channel inhibitors suppressed cysteine uptake but not cytokine production. We conclude that upon antigen recognition, T cells require CxHc to sustain their clonal expansion.
Singlet Oxygen Lifetime in Vitamin E Emulsion Depends on the Oil-Droplet Size
Authors: Ohara Keishi , Origuchi Takashi , Nagaoka Shin-ichi 
Published: March 2010

Abstract
The singlet oxygen (1O2) behavior in emulsions dispersing natural vitamin E (VE) (α-, β-, γ-, and δ-tocopherols) was investigated by measuring time-profiles of 1O2 phosphorescence. The 1O2 rise and decay dynamics noticeably reflected the existence of VE oil-droplets. The decay rate constant (kd) in the α-tocopherol emulsion decreased with increase of VE concentration ([VE]), and became roughly constant in [VE] ≥ 5 × 10−4 M. This kd behavior correlated to the oil-droplet diameter measured by dynamic light scattering. The droplet diameter increased rapidly from 270 to 430 nm with increase of [VE], and reached the limit for dispersing in [VE] ≥ 5 × 10−4 M. This result means that the 1O2 surroundings became more hydrophobic with increase of droplet size. On the other hand, in the emulsions dispersing tocopherols other than α-tocopherol, the kd values were roughly constant, indicating that the oil-droplets did not contribute to 1O2 quenching. The droplet diameter in the δ-tocopherol emulsion was around 212–243 nm and was much smaller than that in the α-tocopherol emulsion. The peculiar results observed in the α-tocopherol emulsion should be due to the large hydrophobicity of α-tocopherol which has two methyl-groups neighboring the OH group.
Calorimetric Study of Correlated Ligand Dynamics in Mixed-Valence MMX Chain Complex [{Ni2(n-BuCS2)4}I]
Authors: Ikeuchi Satoaki , Yamamura Yasuhisa , Yoshida Yuji , Mitsumi Minoru , Toriumi Koshiro , Saito Kazuya 
Published: March 2010

Abstract
Heat capacity of a mixed-valence complex having a one-dimensional chain structure, [{Ni2(n-BuCS2)4}I] (n-Bu = butyl group), was measured between 10 and 325 K by adiabatic calorimetry. Anomalies due to phase transitions were detected around 135 and 260 K. The anomaly around 260 K was of multiple-peaks. The excess entropy acquired below the phase transition around 260 K is much smaller than the simple estimate based on the structural disorder found in the crystal structure, implying the presence of motional correlation in dynamics of n-BuCS2 ligands. Through the comparison with the corresponding Pt complex, [{Pt2(n-BuCS2)4}I], the phase transition around 135 K is also discussed in relation to the absence in the present complex of a spin-Peierls transition observed in other members of Ni complexes with similar chain structures.
Heteronuclear Double Bonds E=E′ (E = Heavy Group 14 Element, E′ = Group 13–16 Element)
Authors: Lee Vladimir Ya , Sekiguchi Akira , Escudié Jean , Ranaivonjatovo Henri 
Published: March 2010

Abstract
A number of compounds with heteronuclear double bonds between heavy elements of groups 13, 14, 15, and 16 have been isolated and characterized in the last three decades; they are kinetically stabilized by the use of bulky substituents or thermodynamically stabilized by intra- or intermolecular coordination. They are fascinating compounds in respect of their unusual chemical properties, being very useful building blocks in organometallic chemistry.
Temperature-dependent Emission of Copper(I) Phenanthroline Complexes with Bulky Substituents: Estimation of an Energy Gap between the Singlet and Triplet MLCT States
Authors: Asano Motoko S , Tomiduka Kazuhito , Sekizawa Keita , Yamashita Ken-ichi , Sugiura Ken-ichi 
Published: March 2010

Abstract
Temperature dependence of emission from bis(2,9-di-tert-butyl-1,10-phenanthroline)copper(I) ([Cu(dtbp)2]+) as well as several other copper(I) bis(phenanthroline) complexes was measured between 190 and 300 K. An analysis based on a Boltzmann distribution model gives an energy gap between 1MLCT and 3MLCT excited states as 790 cm−1 for [Cu(dtbp)2]SbF6. The contribution of the delayed fluorescence largely depends on the ligand substituents.
Enantioselective Michael Reaction of Malonates and α,β-Unsaturated Aldehydes Using a trans-4-Hydroxyproline Derived Organocatalyst
Authors: Sato Hisayuki , Nagashima Fumiaki , Oriyama Takeshi 
Published: March 2010

Abstract
Asymmetric Michael addition of malonates to various α,β-unsaturated aldehydes using an organocatalyst derived from trans-4-hydroxyproline in MeOH proceeds smoothly to afford the corresponding Michael adducts in high yields with high to excellent enantioselectivities.
Luminescence Study of Thioamide-based Pincer Palladium Complexes in Poly(vinylpyrrolidone) Matrix
Authors: Ogawa Yasuyuki , Taketoshi Ayako , Kuwabara Junpei , Okamoto Ken , Fukuda Takashi , Kanbara Takaki 
Published: March 2010

Abstract
Pincer palladium complexes bearing secondary thioamide units exhibit strong phosphorescence at room temperature upon incorporation into poly(vinylpyrrolidone) matrix; a hybrid film shows reversible switching of luminescence upon exposure to volatile organic compounds.
Inexpensive Synthesis of Silicalite-1 Membranes with High Pervaporation Performance
Authors: Zhou Rongfei , Zhu Meihua , Chen Xiangshu , Kita Hidetoshi 
Published: March 2010

Abstract
Good-intergrown silicalite-1 membranes with high ethanol permselectivity were prepared from a hyperdiluted solution with H2O/SiO2 ratio of 800 and an inexpensive template of tetrapropylammonium bromide (TPABr) on seeded mullite tubes.
Optically Transparent Sulfur-containing Semi-alicyclic Polyimide with High Refractive Index
Authors: Nakagawa Yu , Ogura Tomohito , Higashihara Tomoya , Ueda Mitsuru 
Published: March 2010

Abstract
Sulfur-containing semi-alicyclic polyimides (PIs) with high refractive indices up to 1.7272 at 632.8 nm have been prepared by the Michael polyaddition of sulfur-containing bismaleimides (SBMIs) with 4,4′-thiobis(benzenethiol) (TBT). These PIs also showed high transparency in the visible region, low birefringence (Δn), and a high glass transition temperature.
Design and Synthesis of New Linker Units for Covalently Immobilizing Organic Functional Molecules
Authors: Fukaya Norihisa , Onozawa Shun-ya , Ueda Masae , Saitou Kaori , Takagi Yukio , Sakakura Toshiyasu , Yasuda Hiroyuki 
Published: March 2010

Abstract
The design and synthesis of a new linker unit that will enable uniform and robust immobilization of organic functional molecules onto silica supports is described. This linker unit works as a rigid scaffold to prevent grafted organic functional moieties from leaving the support.
Minimal Residual Disease Detection by Flow Cytometry in Adult T-Cell Leukemia/Lymphoma
Authors: Shao Haipeng , Yuan Constance M. , Xi Liqiang , Raffeld Mark , Morris John C. , Janik John E. , Stetler-Stevenson Maryalice 
Published: March 2010

AbstractLittle information exists regarding the detection of minimal residual disease (MRD) in adult T-cell leukemia/lymphoma (ATLL). We evaluated 75 peripheral blood samples from 17 ATLL cases using flow cytometry (FC); 50 of the samples were concurrently evaluated by polymerase chain reaction (PCR) for clonal T-cell receptor γ chain (TRG) gene rearrangement and the presence of human T-cell lymphotropic virus-1 proviral sequences. Residual ATLL cells were identified using a multiparametric approach to identify aberrant T-cell immunophenotypes. Malignant T cells were CD4+, CD3 dim+, CD26–, CD25 bright, CD7+, and CD27+, with occasional dim expression of CD2 or CD5. FC exhibited a high sensitivity, detecting as few as 0.29% ATLL cells/WBC (4.9 cells/μL) in the peripheral blood. PCR for TRG gene rearrangement was slightly more sensitive, and FC and PCR complemented each other in detecting MRD. In 2 patients, there was complete remission; 4 patients had disease refractory to therapy, and 3 died; 11 others had persistent disease with variable numbers of ATLL cells in the peripheral blood. Higher levels of ATLL cells appeared to correlate with disease severity. FC detection of aberrant T cells permits sensitive and quantitative monitoring of MRD in ATLL.
Fifth International Symposium on Safety in Ice Hockey
Authors: Greenwald Richard M. , Ashare Alan B. 
Published: March 2010

Description
The latest volume in this comprehensive series enhances our understanding of both the injuries incurred in the game of ice hockey and of the techniques used to decrease the risk of these injuries.
Twenty-one peer-reviewed papers cover injury prevention and decreasing the risk of catastrophic injuries. Half of the papers in this book cover head and neck injuries, focusing on their analysis, prevention, and treatment of concussions.
The four approaches to achieve these objectives include
These papers were written by experts in their fields, including researchers in a diverse group of fields, including sports medicine, biokinetics, mechanical engineering, neuropsychology, sports litigation, and sports epidemiology.
Twelfth International Symposium on Flammability and Sensitivity of Materials in Oxygen-Enriched Atmospheres
Authors: Barthélémy Hervé , Steinberg Theodore A. , Binder Christian , Smith Sarah 
Published: March 2010

Description
Twenty-eight peer-reviewed papers cover
STP 1522 provides a diverse source of new information to the air separation industry, oxygen manufacturers, manufacturers of components for oxygen and other industrial gases service, manufacturers of materials intended for oxygen and other industrial gases service, and users of oxygen and oxygen-enriched atmospheres. It covers the aerospace, medical, industrial gases, chemical processing, steel and metals refining industries, as well as to military, commercial, and recreational diving.
What Constitutes Reasonable Evidence of Efficacy and Effectiveness to Guide Oncology Treatment Decisions?
Authors: Sargent Daniel 
Published: March 2010

Abstract
The need to practice evidence-based medicine is the current prevailing paradigm within the medical community. Evidence to guide practice can and should come from a variety of sources, including clinical trials, observational studies, and meta-analyses of both or either. This paper discusses the relative strengths and weaknesses of data that arise from these various sources. The different types of evidence required to demonstrate “efficacy” versus “effectiveness,” a critical and often overlooked distinction, are discussed. In the genomic age, in which targeted therapies with or without specific biomarkers are emerging in cancer care, new approaches are necessary to generate the evidence required for decision making.