bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluorescence from the A2Σ+state suggests a non-Franck–Condon N2O+•vibrational state population after keV collisional activation with helium
Authors: Lin Yawei , Mayer Paul M. 
Published: March 2011

A commercial analytical mass spectrometer coupled with a spectrograph and charge-coupled device (CCD) detector was used to obtain the collision-induced emission (CIE) spectra (190–1020 nm) from ion–molecule collisions between N2O+•and He at laboratory frame collision energies of 4–8 keV. The observed emissions were from the A2Σ+ → X2Π+system of N2O+•, excited fragments of the parent molecule, and the target gas. The relative emission intensities of the N2O+•ions and their fragments were independent of the ion translational energy within the 4–8 keV range, confirming the curve-crossing mechanism for translational-to-internal energy transfer in this system. Band emission intensities of [Formula: see text] and [Formula: see text] relative to the [Formula: see text] band within the N2O+•(A → X) system have been measured and compared with reference data. The results indicated that the collisionally excited ion has a decidedly non-Franck–Condon vibrational state distribution.
Photochromic benzo[g]quinoxalines
Authors: Rakotomalala Muriel , Katz Michael , Voisin Emilie , Pace Tamara C. S. , Bohne Cornelia , Williams Vance E. 
Published: March 2011

The photochromism of two 2,3-diarylbenzo[g]quinoxaline derivatives was explored. Irradiating 2,3-diphenylbenzo[g]quinoxaline with 350 nm light led to the formation of its photodimer, which could be reverted to its monomers either thermally or photochemically.The resulting photodimer absorbs at a longer wavelength than analogous dianthracene derivatives. 2,3-Dipyridylbenzo[g]quinoxaline was also observed to undergo photodimerization. The ability of these readily prepared benzoquinoxaline derivatives to undergo [4 + 4]-photocycloaddition reactions makes them attractive alternatives to anthracene derivatives.
Modulation of metabolic and cardiac dysfunctions by insulin sensitizers and angiotensin receptor blocker in rat model of type 2 diabetes mellitus
Authors: Hussein Abd El-Aziz M. , Omar Nisereen M. , Sakr Hussein , Elsamanoudy Ayman Z. , Shaheen Dalia 
Published: March 2011

The objective of this study was to investigate the modulation of metabolic dysfunctions, adiponectin levels, and cardiac dysfunctions of type 2 diabetes mellitus (T2DM) by a combination of the insulin sensitizer rosiglitazone and angiotensin receptor blocker telmisartan in an experimental rat model. Fifty male adult Sprague–Dawley rats were divided equally into 5 groups. Group I: fed normal chow; served as normal control group. Groups II–V: fed a high-fat diet (HFD) for 2 weeks, followed by injection of streptozotocin (STZ; 35 mg/kg) to create a model of T2DM. Group II: treated with vehicle. Group III: treated with rosiglitazone (4 mg/kg). Group IV: treated with telmisartan (5 mg/kg). Group V: treated with both agents. Untreated HFD-STZ rats showed elevated fasting blood glucose, insulin, homeostasis model assessment (HOMA) index, triglycerides (TGs), low-density lipoprotein cholesterol (LDL), and total serum cholesterol (TC), with a decrease in high-density lipoprotein cholesterol (HDL) and adiponectin levels (p < 0.001). Rosiglitazone exerted more improvement in all parameters than telmisartan did, and a combination of both did not augment the improvement further, except for TGs and adiponectin. For the isolated atrial study, a combination of rosiglitazone and telmisartan corrected the responses of the atria of HFD-STZ rats to the negative inotropic effect induced by adenosine better than either one did alone, whereas this combination, surprisingly, significantly attenuated the positive inotropic response to β-adrenoreceptor and α-adrenoreceptor agonists. In conclusion, rosiglitazone significantly improved the metabolic and cardiac dysfunctions in T2DM. Moreover, a combination of rosiglitazone and telmisartan offered more improvement in serum TGs and adiponectin, and restored the atrial inotropic response to adenosine. Surprisingly, this combination significantly attenuates the positive inotropic response to α1-adrenoreceptor and β-adrenoreceptor agonists.
Enalapril decreases cardiac mass and fetal gene expression without affecting the expression of endothelin-1, transforming growth factor β-1, or cardiotrophin-1 in the healthy normotensive rat
Authors: Mackovicova Katarina , Gazova Andrea , Kucerova Dana , Gajdacova Beata , Klimas Jan , Ochodnicky Peter , Goncalvesova Eva , Kyselovic Jan , Krenek Peter 
Published: March 2011

Angiotensin II can induce cardiac hypertrophy by stimulating the release of growth factors. ACE inhibitors reduce angiotensin II levels and cardiac hypertrophy, but their effects on the healthy heart are largely unexplored. We hypothesized that ACE inhibition decreases left ventricular mass in normotensive animals and that this is associated with altered expression of cardiac fetal genes, growth factors, and endothelial nitric oxide synthase (eNOS). Wistar rats (n = 7 per group) were orally administered with enalapril twice daily for a total daily dose of 5 mg·kg–1·d–1(ENAP5) or 15 mg·kg–1·d–1(ENAP15) or vehicle. Systolic blood pressure was measured by the tail-cuff method. Left ventricular expression of cardiac myosin heavy chain-α (MYH6) and -β (MYH7), atrial natriuretic peptide (ANP), endothelin-1 (ET-1), transforming growth factor β-1 (TGFβ-1), cardiotrophin-1 (CT-1), and renal renin were examined by real-time PCR, and eNOS using Western blot. Blood pressure was decreased only in ENAP15 animals (p < 0.05 vs. Control), whereas left ventricular mass decreased after both doses of enalapril (p < 0.05 vs. Control). MYH7 and ANP were reduced in ENAP15, while no changes in ET-1, TGFβ-1, CT-1, and MYH6 mRNA or eNOS protein were observed. Renal renin dose-dependently increased after enalapril treatment. Enalapril significantly decreased left ventricular mass even after 1 week treatment in the normotensive rat. This was associated with a decreased expression of the fetal genes MYH7 and ANP, but not expression of ET-1, CT-1, or TGFβ-1.
Heterosis and outbreeding depression between strains of young-of-the-year brook trout (Salvelinus fontinalis)
Authors: Granier S. , Audet C. , Bernatchez L. 
Published: March 2011

Brook trout ( Salvelinus fontinalis (Mitchill, 1814)) supports a lucrative fish aquaculture industry in Quebec and production of this species is mainly oriented to stock enhancement supporting sport fisheries. The aim of this study was to verify the expression of interstrain heterosis, i.e., increased performance of first generation hybrid progeny, during the first stages of development in brook trout. Two wild populations that were recently introduced to fish production in Quebec, the Laval (L) and the Rupert (R) strains, and a domestic strain (D) that is present in most Quebec fish farms were used in this study. The growth of 72 full-sibling families, representing three pure (♀D × ♂D, ♀L × ♂L, ♀R × ♂R) and five hybrid (♀D × ♂L, ♀D × ♂R, ♀L × ♂D, ♀L × ♂R, ♀R × ♂L) cross types, were surveyed from hatching to 2136 degree-days. Both heterosis and outbreeding depression were observed, depending on the hybrid cross type. The occurrence of heterosis was dependent on the developmental stage, and growth advantage at a very early developmental stage did not necessarily translate into bigger size later on. Outbreeding depression in growth (mass or length) was much less common than heterosis, and when occurring, it varied from 9.2% to 33.3% compared with 9.0% to 88.2% improvement in growth traits for heterosis. The results indicate that in early development, there was higher occurrence of heterosis relative to fish mass than to fish length and that, overall, the occurrence of heterosis was unpredictable.
JUSTIFICATION OF POINT ELECTRODE MODELS IN ELECTRICAL IMPEDANCE TOMOGRAPHY
Authors: HANKE MARTIN , HARRACH BASTIAN , HYVÖNEN NUUTTI 
Published: March 2011

The most accurate model for real-life electrical impedance tomography is the complete electrode model, which takes into account electrode shapes and (usually unknown) contact impedances at electrode-object interfaces. When the electrodes are small, however, it is tempting to formally replace them by point sources. This simplifies the model considerably and completely eliminates the effect of contact impedance. In this work we rigorously justify such a point electrode model for the important case of having difference measurements ("relative data") as data for the reconstruction problem. We do this by deriving the asymptotic limit of the complete model for vanishing electrode size. This is supplemented by an analogous result for the case that the distance between two adjacent electrodes also tends to zero, thus providing a physical interpretation and justification of the so-called backscattering data introduced by two of the authors.
A Simple Approach to Cancer Therapy Afforded by Multivalent Pseudopeptides That Target Cell-Surface Nucleoproteins
Authors: Destouches Damien , Page Nicolas , Hamma-Kourbali Yamina , Machi Valérie , Chaloin Olivier , Frechault Sophie , Birmpas Charalampos , Katsoris Panagiotis , Beyrath Julien , Albanese Patricia , Maurer Marie , Carpentier Gilles , Strub Jean-Marc , Van Dorsselaer Alain , Muller Sylviane , Bagnard Dominique , Briand Jean Paul , Courty José 
Published: March 2011

Abstract
Recent studies have implicated the involvement of cell surface forms of nucleolin in tumor growth. In this study, we investigated whether a synthetic ligand of cell-surface nucleolin known as N6L could exert antitumor activity. We found that N6L inhibits the anchorage-dependent and independent growth of tumor cell lines and that it also hampers angiogenesis. Additionally, we found that N6L is a proapoptotic molecule that increases Annexin V staining and caspase-3/7 activity in vitro and DNA fragmentation in vivo. Through affinity isolation experiments and mass-spectrometry analysis, we also identified nucleophosmin as a new N6L target. Notably, in mouse xenograft models, N6L administration inhibited human tumor growth. Biodistribution studies carried out in tumor-bearing mice indicated that following administration N6L rapidly localizes to tumor tissue, consistent with its observed antitumor effects. Our findings define N6L as a novel anticancer drug candidate warranting further investigation. Cancer Res; 71(9); 3296–305. ©2011 AACR.
Aberrant Expression of OX1 Receptors for Orexins in Colon Cancers and Liver Metastases: an Openable Gate to Apoptosis
Authors: Voisin Thierry , El Firar Aadil , Fasseu Magali , Rouyer-Fessard Christiane , Descatoire Véronique , Walker Francine , Paradis Valérie , Bedossa Pierre , Henin Dominique , Lehy Thérèse , Laburthe Marc 
Published: March 2011

Abstract
Resistance to apoptosis is a recurrent theme in colon cancer. We have shown previously that the 7-transmembrane spanning receptor OX1R for orexins promotes robust apoptosis in the human colon cancer cell line HT29 through an entirely novel mechanism involving phosphorylation of tyrosine-based motifs in OX1R. Here, we investigated the status of OX1R in a large series of human colorectal tumors and hepatic metastases. All primary colorectal tumors regardless of their localization and Duke's stages and all hepatic metastases tested expressed OX1R mRNA and/or protein. In sharp contrast, adjacent normal colonocytes or hepatocytes as well as control normal tissues were negative. Next, we showed that nine human colon cancer cell lines established from primary tumors or metastases expressed OX1R mRNA and underwent important apoptosis on orexin-A challenge. Most interestingly, orexin-A also promoted robust apoptosis in cells that are resistant to the most commonly used drug in colon cancer chemotherapy, 5-fluorouracil. When human colon cancer cells were xenografted in nude mice, orexin-A administered at day 0 strongly slowed the tumor growth and even reversed the development of established tumors when administered 7 days after cell inoculation. Orexin-A also acts by promoting tumor apoptosis in vivo because caspase-3 is activated in tumors on orexin treatment of nude mice. These findings support that OX1R is an Achilles heel of colon cancers, even after metastasis or chemoresistance. They suggest that OX1R agonists might be novel candidates for colon cancer therapy. Cancer Res; 71(9); 3341–51. ©2011 AACR.
Effects of mTOR Inhibitor Everolimus (RAD001) on Bladder Cancer Cells
Authors: Chiong Edmund , Lee I-Ling , Dadbin Ali , Sabichi Anita L. , Harris Loleta , Urbauer Diana , McConkey David J. , Dickstein Rian J. , Cheng Tiewei , Grossman H. Barton 
Published: March 2011

Abstract
Purpose: We investigated the effect of the mTOR inhibitor RAD001 (everolimus) on human bladder cancer (BC) cells in vitro and in vivo.
Experimental Design: The effect of RAD001 on the growth of UM-UC-3, UM-UC-6, UM-UC-9, and UM-UC-14 BC cells were assessed by crystal violet and [3H]thymidine incorporation assays. Flow cytometric cell-cycle analyses were done to measure the apoptotic cell fraction. Protein synthesis was measured using tritium-labeled leucine incorporation assays. The effects of RAD001 on the mTOR pathway were analyzed by Western blotting. To test the effects of RAD001 in vivo, UM-UC-3, UM-UC-6, and UM-UC-9 cells were subcutaneously implanted into nude mice. Tumor-bearing mice were treated orally with RAD001 or placebo. Tumors were harvested for immunohistochemical analysis.
Results: In vitro, RAD001 transiently inhibited BC cell growth in a dose-dependent manner. This effect was augmented by re-treatment of cells after 3 days. UM-UC-14 cells were the most sensitive to RAD001, whereas UM-UC-9 cells were the least sensitive. After re-treatment with RAD001, only sensitive cell lines showed G1-phase arrest, with no evidence of apoptosis. RAD001 significantly inhibited the growth of tumors that were subcutaneously implanted in mice. Inhibition of protein synthesis through the S6K and 4EBP1 pathways seems to be the main mechanism for the RAD001-induced growth inhibition. However, inhibition of angiogenesis was the predominant mechanism of the effect of RAD001 on UM-UC-9 cells.
Conclusions: The mTOR inhibitor RAD001 inhibits growth of BC cells in vitro. RAD001 is effective in treating BC tumors in an in vivo nude mouse model despite the heterogeneity of in vitro responses. Clin Cancer Res; 17(9); 2863–73. ©2011 AACR.
Genomic Analysis Reveals the Molecular Heterogeneity of Ovarian Clear Cell Carcinomas
Authors: Tan David S.P. , Iravani Marjan , McCluggage W. Glenn , Lambros Maryou B.K. , Milanezi Fernanda , Mackay Alan , Gourley Charles , Geyer Felipe C. , Vatcheva Radost , Millar Joanne , Thomas Karen , Natrajan Rachael , Savage Kay , Fenwick Kerry , Williams Alistair , Jameson Charles , El-Bahrawy Mona , Gore Martin E. , Gabra Hani , Kaye Stanley B. , Ashworth Alan , Reis-Filho Jorge S. 
Published: March 2011

Abstract
Purpose: Ovarian clear cell carcinomas (OCCC) are a drug-resistant and aggressive type of epithelial ovarian cancer. We analyzed the molecular genetic profiles of OCCCs to determine whether distinct genomic subgroups of OCCCs exist.
Experimental design: Fifty pure primary OCCCs were subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). Unsupervised hierarchical clustering using Ward's linkage analysis was performed to identify genomic subgroups of OCCCs. Survival analysis was performed using Kaplan–Meier method and log-rank test. Cox-regression analysis was used to identify independent predictors of outcome. Differentially amplified regions between genomic subgroups of OCCCs were identified using a multi-Fisher's exact test.
Results: Hierarchical cluster analysis revealed two distinct clusters of OCCCs with different clinical outcomes. Patients from cluster-1 had a significantly shorter median progression-free survival (PFS) than those from cluster-2 (11 vs. 65 months, P = 0.009), although estimates for ovarian cancer–specific survival (OCS) did not reach statistical significance (P = 0.065). In multivariate analysis, suboptimal debulking surgery and genomic cluster were independently prognostic for PFS. Recurrently amplified genomic regions with a significantly higher prevalence in cluster-1 than cluster-2 OCCCs were identified and validated. HER2 gene amplification and protein overexpression was observed in 14% of OCCCs, suggesting that this may constitute a potential therapeutic target for a subgroup of these tumors.
Conclusions: OCCCs constitute a heterogeneous disease at the genomic level despite having similar histological features. The pattern of genomic aberrations in subgroups of OCCCs is of clinical significance. We have identified recurrently amplified regions that may harbor potential therapeutic targets for subgroups of OCCCs. Clin Cancer Res; 17(6); 1521–34. ©2011 AACR.
Role of ERK-BIM and STAT3-Survivin Signaling Pathways in ALK Inhibitor–Induced Apoptosis in EML4-ALK–Positive Lung Cancer
Authors: Takezawa Ken , Okamoto Isamu , Nishio Kazuto , Jänne Pasi A. , Nakagawa Kazuhiko 
Published: March 2011

Abstract
Purpose: EML4-ALK (echinoderm microtubule-associated protein–like 4 anaplastic lymphoma kinase) was recently identified as a transforming fusion gene in non–small cell lung cancer. The purpose of the present study was to characterize the mechanism of malignant transformation by EML4-ALK.
Experimental Design: We established NIH 3T3 cells that stably express variant 1 or 3 of EML4-ALK and examined the signaling molecules that function downstream of EML4-ALK.
Results: Forced expression of EML4-ALK induced marked activation of extracellular signal–regulated kinase (ERK) and STAT3, but not that of AKT. Inhibition of ERK or STAT3 signaling resulted in substantial attenuation of the proliferation of cells expressing either variant of EML4-ALK, suggesting that these signaling pathways function downstream of EML4-ALK in lung cancer cells. The specific ALK inhibitor TAE684 induced apoptosis that was accompanied both by upregulation of BIM, a proapoptotic member of the Bcl-2 family, and by downregulation of survivin, a member of the inhibitor of apoptosis protein (IAP) family, in EML4-ALK–expressing NIH 3T3 cells as well as in H3122 human lung cancer cells harboring endogenous EML4-ALK. Depletion of BIM and overexpression of survivin each inhibited TAE684-induced apoptosis, suggesting that both upregulation of BIM and downregulation of survivin contribute to TAE684-induced apoptosis in EML4-ALK–positive lung cancer cells. Furthermore, BIM and survivin expression was found to be independently regulated by ERK and STAT3 signaling pathways, respectively.
Conclusions: ALK inhibitor–induced apoptosis is mediated both by BIM upregulation resulting from inhibition of ERK signaling as well as by survivin downregulation resulting from inhibition of STAT3 signaling in EML4-ALK–positive lung cancer cells. Clin Cancer Res; 17(8); 2140–8. ©2011 AACR.
Genomic Loss ofmiR-486Regulates Tumor Progression and theOLFM4Antiapoptotic Factor in Gastric Cancer
Authors: Oh Hue-Kian , Tan Angie Lay-Keng , Das Kakoli , Ooi Chia-Huey , Deng Nian-Tao , Tan Iain BeeHuat , Beillard Emmanuel , Lee Julian , Ramnarayanan Kalpana , Rha Sun-Young , Palanisamy Nallasivam , Voorhoeve P. Mathijs , Tan Patrick 
Published: March 2011

AbstractPurpose: MicroRNAs (miRNA) play pivotal oncogenic and tumor-suppressor roles in several human cancers. We sought to discover novel tumor-suppressor miRNAs in gastric cancer (GC).Experimental Design: Using Agilent miRNA microarrays, we compared miRNA expression profiles of 40 primary gastric tumors and 40 gastric normal tissues, identifying miRNAs significantly downregulated in gastric tumors.Results: Among the top 80 miRNAs differentially expressed between gastric tumors and normals (false discovery rate &lt; 0.01), we identified hsa-miR-486 (miR-486) as a significantly downregulated miRNA in primary GCs and GC cell lines. Restoration of miR-486 expression in GC cell lines (YCC3, SCH and AGS) caused suppression of several pro-oncogenic traits, whereas conversely inhibiting miR-486 expression in YCC6 GC cells enhanced cellular proliferation. Array-CGH analysis of 106 primary GCs revealed genomic loss of the miR-486 locus in approximately 25% to 30% of GCs, including two tumors with focal genomic losses specifically deleting miR-486, consistent with miR-486 playing a tumor-suppressive role. Bioinformatic analysis identified the secreted antiapoptotic glycoprotein OLFM4 as a potential miR-486 target. Restoring miR-486 expression in GC cells decreased endogenous OLFM4 transcript and protein levels, and also inhibited expression of luciferase reporters containing an OLFM4 3′ untranslated region with predicted miR-486 binding sites. Supporting the biological relevance of OLFM4 as a miR-486 target, proliferation in GC cells was also significantly reduced by OLFM4 silencing.Conclusions: miR-486 may function as a novel tumor-suppressor miRNA in GC. Its antioncogenic activity may involve the direct targeting and inhibition of OLFM4. Clin Cancer Res; 17(9); 2657–67. ©2011 AACR.
Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of TH-302, a Hypoxia-Activated Prodrug, in Patients with Advanced Solid Malignancies
Authors: Weiss Glen J. , Infante Jeffrey R. , Chiorean E. Gabriela , Borad Mitesh J. , Bendell Johanna C. , Molina Julian R. , Tibes Raoul , Ramanathan Ramesh K. , Lewandowski Karen , Jones Suzanne F. , Lacouture Mario E. , Langmuir Virginia K. , Lee Hank , Kroll Stew , Burris Howard A. 
Published: March 2011

Abstract
Purpose: The objectives of this phase 1, first-in-human study were to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary activity of the hypoxia-activated prodrug TH-302 in patients with advanced solid tumors.
Experimental Design: TH-302 was administered intravenously over 30 to 60 minutes in two regimens: three times weekly dosing followed by 1 week off (arm A) and every 3-week dosing (arm B).
Results: Fifty-seven patients enrolled (arm A: N = 37 and arm B: N = 20). The TH-302 dose was escalated from 7.5 to 670 mg/m2 in arm A and from 670 to 940 mg/m2 in arm B. The most common adverse events were nausea, skin rash, fatigue, and vomiting. Hematologic toxicity was mild and limited. Grade 3 skin and mucosal toxicities were dose limiting at 670 mg/m2 in arm A; the MTD was 575 mg/m2. In arm B, grade 3 fatigue and grade 3 vaginitis/proctitis were dose limiting at 940 mg/m2; the MTD was 670 mg/m2. Plasma concentrations of TH-302 and the active metabolite Br-IPM (brominated version of isophosphoramide mustard) increased proportionally with dose. Two partial responses were noted in patients with metastatic small cell lung cancer (SCLC) and melanoma in arm A at 480 and 670 mg/m2. Stable disease was observed in arms A and B in 18 and 9 patients, respectively.
Conclusions: The MTD of TH-302 was 575 mg/m2 weekly and 670 mg/m2 every 3 weeks. Skin and mucosal toxicities were DLTs. On the basis of responses in metastatic melanoma and SCLC, further investigations in these indications were initiated. Clin Cancer Res; 17(9); 2997–3004. ©2011 AACR.