bluuebunny/crossref_metadata_2025_split huggingface dataset:
Humanized Anti-Interleukin-6 Receptor Antibody Suppresses Tumor Angiogenesis and In vivo Growth of Human Oral Squamous Cell Carcinoma
Authors: Shinriki Satoru , Jono Hirofumi , Ota Kazutoshi , Ueda Mitsuharu , Kudo Mareina , Ota Tomoko , Oike Yuichi , Endo Motoyoshi , Ibusuki Mutsuko , Hiraki Akimitsu , Nakayama Hideki , Yoshitake Yoshihiro , Shinohara Masanori , Ando Yukio 
Published: August 2009

Abstract
Purpose: The biological effect of interleukin-6 (IL-6) signaling in oral squamous cell carcinoma (OSCC) and whether IL-6 receptor (IL-6R)-mediated signaling can be a therapeutic target for OSCC are unclear. The aim of this study was to investigate the effects of inhibition of IL-6R–mediated signaling on OSCC progression and to evaluate the availability of tocilizumab, a humanized antihuman IL-6R antibody, as a therapeutic agent for OSCC.
Experimental Design: We evaluated expression levels of IL-6 and IL-6R in 58 OSCC tissues and 4 OSCC cell lines by real-time quantitative reverse transcription-PCR and/or immunohistochemstry. We investigated the effects of tocilizumab on OSCC growth in vitro and in xenografts. Xenografts were analyzed by immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 (pSTAT3), Ki-67, and CD31, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay was done.
Results: Expression levels of IL-6 at both mRNA and protein levels in OSCC tissues were significantly higher than those in normal mucosal tissues. In addition, OSCC cell lines expressed higher levels of both IL-6 and IL-6R mRNA than did HaCaT keratinocytes. Tocilizumab significantly reduced in vivo growth of SAS cells with a drastic reduction of STAT3 phosphorylation in tumor cells in mice. Inhibition of IL-6 signaling significantly decreased vascular endothelial growth factor mRNA expression in SAS, and microvessel density and vessel diameter in SAS tumors in tocilizumab-treated mice.
Conclusions: Therapeutic approaches targeting IL-6R by tocilizumab may be effective for OSCC treatment by at least inhibiting angiogenesis. (Clin Cancer Res 2009;15(17):5426–34)
Decreased Blood Flow with Increased Metabolic Activity: A Novel Sign of Pancreatic Tumor Aggressiveness
Authors: Komar Gaber , Kauhanen Saila , Liukko Kaisa , Seppänen Marko , Kajander Sami , Ovaska Jari , Nuutila Pirjo , Minn Heikki 
Published: August 2009

Abstract
Purpose: To study blood flow (BF) and metabolism in normal pancreas and in different pancreatic lesions. We then determined the effect of these biomarkers on outcome in patients with pancreatic cancer.
Experimental Design: Oxygen-15–labeled water and fluorodeoxyglucose positron emission tomography/computed tomography scans were used in 26 patients with a suspicion of pancreatic cancer to measure pancreatic BF and metabolism. In addition, the ratio of standardized uptake value to BF (SUV/BF) was calculated. Patients were divided into three groups: patients with a finding of normal pancreas (n = 7), benign lesions (n = 8), and malignant tumors (n = 11).
Results: Patients with benign and malignant pancreatic tumors had decreased BF of the lesion by 48% and 60%, respectively, compared with patients with normal pancreatic tissue. SUVmax was 3-fold higher in malignant tumors compared with both benign lesions and normal pancreas (P &lt; 0.05). In contrast, the SUVmax of patients with benign lesions and normal pancreas did not differ. The SUV/BF ratio was significantly higher in malignant lesions than in benign lesions or in patients with normal pancreas (P &lt; 0.05). In patients with cancer, high SUV/BF ratio was a stronger predictor of poor survival compared with high metabolism or lower-than-normal pancreatic BF.
Conclusions: BF in pancreatic cancer is significantly reduced compared with the normal pancreas, which may in part explain the poor success of both radiotherapy and chemotherapy. We suggest that the composite measurement of BF and metabolism in pancreatic cancer could serve as a novel tool in the planning of treatments targeting vasculature. (Clin Cancer Res 2009;15(17):5511–7)
A Phase I Study of a 2-Day Lapatinib Chemosensitization Pulse Preceding Nanoparticle Albumin-Bound Paclitaxel for Advanced Solid Malignancies
Authors: Chien Amy J. , Illi Julie A. , Ko Andrew H. , Korn Wolfgang M. , Fong Lawrence , Chen Lee-may , Kashani-Sabet Mohammed , Ryan Charles J. , Rosenberg Jonathan E. , Dubey Sarita , Small Eric J. , Jahan Thierry M. , Hylton Nola M. , Yeh Benjamin M. , Huang Yong , Koch Kevin M. , Moasser Mark M. 
Published: August 2009

Abstract
Purpose: Systemic chemotherapy fails to access much of the tumor burden in patients with advanced cancer, significantly limiting its efficacy. In preclinical studies, brief high doses of tyrosine kinase inhibitors (TKI) targeting the human epidermal growth factor receptor (HER) family can prime tumor vasculature for optimal chemotherapeutic delivery and efficacy. This study investigates the clinical relevance of this approach.
Experimental Design: A phase I clinical study of escalating doses of the HER TKI lapatinib given as a 2-day pulse before a weekly infusion of nab-paclitaxel (100 mg/m2) was conducted in patients with advanced solid tumors.
Results: Twenty-five patients were treated. Treatment was associated with grade 1 to 2 toxicities including diarrhea, nausea, rash, neutropenia, neuropathy, fatigue, alopecia, and anemia. The two dose-limiting toxicities were grade 3 vomiting and grade 4 neutropenia, and the maximum tolerated dose of lapatinib was defined as 5250 mg/day in divided doses. Lapatinib concentrations increased with increasing dose. Dynamic Contrast Enhanced Magnetic Resonance Imaging studies in a subset of patients confirmed a decrease in tumor vascular permeability immediately following a lapatinib pulse. Sixty-five percent of evaluable patients experienced a partial or stable response on this therapy, 72% of whom were previously taxane-refractory.
Conclusion: A 2-day pulse of high-dose lapatinib given before weekly nab-paclitaxel is a feasible and tolerable clinical regimen, suitable for testing this novel vascular-priming chemosensitization hypothesis developed in preclinical models. (Clin Cancer Res 2009;15(17):5569–75)
[11C]Choline Positron Emission Tomography in Estrogen Receptor–Positive Breast Cancer
Authors: Contractor Kaiyumars B. , Kenny Laura M. , Stebbing Justin , Al-Nahhas Adil , Palmieri Carlo , Sinnett Dudley , Lewis Jacqueline S. , Hogben Katy , Osman Safiye , Shousha Sami , Lowdell Charles , Coombes R. Charles , Aboagye Eric O. 
Published: August 2009

Abstract
Purpose: Novel radiotracers could potentially allow the identification of clinically aggressive tumor phenotypes. As choline metabolism increases during malignant transformation and progression of human mammary epithelial cells, we examined the ability of [11C]choline (CHO) positron emission tomography imaging to detect clinically aggressive phenotype in patients with estrogen receptor (ER)–positive breast cancer in vivo.
Experimental Design: CHO positron emission tomography was done in 32 individuals with primary or metastatic ER–positive breast cancer. Semiquantitative (standardized uptake value) and fully quantitative (net irreversible transfer rate constant of CHO, Ki) estimates of CHO uptake in the tumors were calculated and compared with tumor grade, size, involved nodes, and also ER, progesterone receptor, Ki-67, and human epidermal growth factor receptor-2 scores.
Results: Breast tumors were well visualized in 30 of 32 patients with good tumor background ratios. A wide range of uptake values were observed in primary and metastatic tumors. CHO uptake variables correlated well with tumor grade. For most imaging variables, a poor association was found with tumor size, ER, progesterone receptor, human epidermal growth factor receptor-2, Ki-67, and nodal status.
Conclusions: CHO showed good uptake in most breast cancers and merits further investigation as a breast cancer imaging agent. (Clin Cancer Res 2009;15(17):5503–10)
Complexity Made Simple in Diffuse Large B-Cell Lymphoma
Authors: Aster Jon , Kutok Jeffery 
Published: August 2009

Abstract
Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease and response to therapy is difficult to predict. An algorithm to sort DLBCL cases using a series of five immunohistochemical markers (GCET1, CD10, BCL6, MUM1, FOXP1) accurately predicts survival in patients treated with current chemotherapeutic regimens. (Clin Cancer Res 2009;15(17):5291–3)
NF-κB activation in endothelial cells is critical for the activity of angiostatic agents
Authors: Tabruyn Sebastien P. , Mémet Sylvie , Avé Patrick , Verhaeghe Catherine , Mayo Kevin H. , Struman Ingrid , Martial Joseph A. , Griffioen Arjan W. 
Published: August 2009

Abstract
In tumor cells, the transcription factor NF-κB has been described to be antiapoptotic and proproliferative and involved in the production of angiogenic factors such as vascular endothelial growth factor. From these data, a protumorigenic role of NF-κB has emerged. Here, we examined in endothelial cells whether NF-κB signaling pathway is involved in mediating the angiostatic properties of angiogenesis inhibitors. The current report describes that biochemically unrelated agents with direct angiostatic effect induced NF-κB activation in endothelial cells. Our data showed that endostatin, anginex, angiostatin, and the 16-kDa N-terminal fragment of human prolactin induced NF-κB activation in endothelial cells in both cultured human endothelial cells and in vivo in a mouse tumor model. It was also found that NF-κB activity was required for the angiostatic activity, because inhibition of NF-κB in endothelial cells impaired the ability of angiostatic agents to block sprouting of endothelial cells and to overcome endothelial cell anergy. Therefore, activation of NF-κB in endothelial cells can result in an unexpected antitumor outcome. Based on these data, the current approach of systemic treatment with NF-κB inhibitors may therefore be revisited because NF-κB activation specifically targeted to endothelial cells might represent an efficient strategy for the treatment of cancer. [Mol Cancer Ther 2009;8(9):2645–54]
Structure and Origin of the Quasi-Biweekly Oscillation over the Tropical Indian Ocean in Boreal Spring
Authors: Wen Min , Li Tim , Zhang Renhe , Qi Yanjun 
Published: August 2009

Abstract
The structure and evolution features of the quasi-biweekly (10–20 day) oscillation (QBWO) in boreal spring over the tropical Indian Ocean (IO) are investigated using 27-yr daily outgoing longwave radiation (OLR) and the National Centers for Environment Prediction–National Center for Atmospheric Research (NCEP–NCAR) reanalysis data. It is found that a convective disturbance is initiated over the western IO and moves slowly eastward. After passing the central IO, it abruptly jumps into the eastern IO. Meanwhile, the preexisting suppressed convective anomaly in the eastern IO moves poleward in the form of double-cell Rossby gyres. The analysis of vertical circulation shows that a few days prior to the onset of local convection in the eastern equatorial IO an ascending motion appears in the boundary layer.
Based on the diagnosis of the zonal momentum equation, a possible boundary layer–triggering mechanism over the eastern equatorial IO is proposed. The cause of the boundary layer convergence and vertical motion is attributed to the free-atmospheric divergence in association with the development of the barotropic wind. It is the downward transport of the background mean easterly momentum by perturbation vertical motion during the suppressed convective phase of the QBWO that leads to the generation of a barotropic easterly—the latter of which further causes the free-atmospheric divergence and, thus, the boundary layer convergence. The result suggests that the local process, rather than the eastward propagation of the disturbance from the western IO, is essential for the phase transition of the QBWO convection over the eastern equatorial IO.
Influence of Ice Crystal Aspect Ratio on the Evolution of Ice Size Spectra during Vapor Depositional Growth
Authors: Sheridan Lindsay M. , Harrington Jerry Y. , Lamb Dennis , Sulia Kara 
Published: August 2009

Abstract
The relationship among aspect ratio, initial size, and the evolution of the size spectrum is explored for ice crystals growing by vapor deposition. Ice crystal evolution is modeled based on the growth of spheroids, and the ice size spectrum is predicted using a model that is Lagrangian in crystal size and aspect ratio. A dependence of crystal aspect ratio on initial size is discerned: more exaggerated shapes are shown to result when the initial crystals are small, whereas more isometric shapes are found to result from initially large crystals. This result is due to the nature of the vapor gradients in the vicinity of the crystal surface. The more rapid growth of the smaller crystals is shown to produce a period during which the size distribution narrows, followed by a broadening led by the initially smallest crystals. The degree of broadening is shown to depend strongly on the primary habit and hence temperature.
Do High-Frequency Eddies Contribute to Low-Frequency Teleconnection Tendencies?*
Authors: Athanasiadis Panos J. , Ambaum Maarten H. P. 
Published: August 2009

Abstract
An isentropic potential vorticity (PV) budget analysis is employed to examine the role of synoptic transients, advection, and nonconservative processes as forcings for the evolution of the low-frequency PV anomalies locally and those associated with the North Atlantic Oscillation (NAO) and the Pacific–North American (PNA) pattern. Specifically, the rate of change of the low-frequency PV is expressed as a sum of tendencies due to divergence of eddy transport, advection by the low-frequency flow (hereafter referred to as advection), and the residual nonconservative processes. The balance between the variances and covariances of these terms is illustrated using a novel vector representation.
It is shown that for most locations, as well as for the PNA pattern, the PV variability is dominantly driven by advection. The eddy forcing explains a small amount of the tendency variance. For the NAO, the role of synoptic eddy fluxes is found to be stronger, explaining on average 15% of the NAO tendency variance. Previous studies have not assessed quantitively how the various forcings balance the tendency. Thus, such studies may have overestimated the role of eddy fluxes for the evolution of teleconnections by examining, for example, composites and regressions that indicate maintenance, rather than evolution driven by the eddies. The authors confirm this contrasting view by showing that during persistent blocking (negative NAO) episodes the eddy driving is relatively stronger.
Pollen-Based Quantitative Reconstruction of Holocene Climate Changes in the Daihai Lake Area, Inner Mongolia, China
Authors: Xu Qinghai , Xiao Jule , Li Yuecong , Tian Fang , Nakagawa Takeshi 
Published: August 2009

Abstract
Vegetation around the Daihai Lake, northern China, is very sensitive to climate changes. In this paper, pollen-based quantitative climate reconstructions using three methods [weighted averaging partial least squares method (WAPLS), modern analog technique (MAT), and pollen response surface method (PRS)] were conducted to obtain robust reconstructions of Holocene climate changes in the Daihai Lake area. The result obtained by the three methods all consistently show the annual precipitation to have been 50–100 mm lower in the early Holocene, 100–200 mm higher in the Mid-Holocene, and 50–100 mm lower again in the late Holocene than at present. The WAPLS and the MAT methods also show quasi-synchronous oscillations of the mean annual temperature (Ta); 1°–2°C lower in the Early Holocene and 1°–3°C higher in the Mid-Holocene than today. The time period from 6200 to 5100 cal yr BP was the wettest and the warmest interval, with an annual precipitation (Pa) greater than 550 mm and mean annual temperature Ta higher than 6.5°C. Several cold and dry events can be identified to occur about 8200, 6000, and 4400 cal yr BP, with an annual precipitation less than 400 mm and a mean annual temperature colder than 4.5°C, respectively. The mean temperature of the warmest month (Tw) as reconstructed using both WAPLS and MAT methods was relatively stable during the Holocene, fluctuating about ±2°C relative to the present level, but the PRS method suggests more varied Tw values in both amplitude and frequency. After 1500 cal yr BP, no consistent pattern can be observed from these three different analyses, probably because of the impact of intensified human disturbances on the natural vegetation. The fluctuations of annual precipitation (Pa) correspond to that observed in Dongge Cave in southern China. The differences might be linked to Indian monsoon and East Asia monsoon climates or caused by the different degree of dating precision, different temporal resolution, and different sensitive response of climate proxies to the climate variations.
Identification of 4 new HLA-DR–restricted minor histocompatibility antigens as hematopoietic targets in antitumor immunity
Authors: Stumpf Anita N. , van der Meijden Edith D. , van Bergen Cornelis A. M. , Willemze Roel , Falkenburg J. H. Frederik , Griffioen Marieke 
Published: August 2009

Abstract
Potent graft-versus-leukemia (GVL) effects can be mediated by donor-derived T cells recognizing minor histocompatibility antigens (mHags) in patients treated with donor lymphocyte infusion (DLI) for relapsed hematologic malignancies after HLA-matched allogeneic stem cell transplantation (alloSCT). Donor-derived T cells, however, may not only induce GVL, but also mediate detrimental graft-versus-host disease (GVHD). Because HLA-class II is under noninflammatory conditions predominantly expressed on hematopoietic cells, CD4+ T cells administered late after alloSCT may selectively confer GVL without GVHD. Although a broad range of different HLA-class I–restricted mHags have been identified, the first 2 autosomal HLA-class II–restricted mHags have only recently been characterized. By screening a recombinant bacteria cDNA expression library, we identified 4 new HLA-class II–restricted mHags recognized by CD4+ T cells induced in a patient with relapsed chronic myeloid leukemia who achieved long-term complete remission and experienced only mild GVHD of the skin after DLI. All CD4+ T cells were capable of recognizing the mHags presented by HLA-DR surface molecules on primary hematopoietic cells, but not on skin-derived (cytokine-treated) fibroblasts. The selective recognition of hematopoietic cells as well as the balanced population frequencies and common HLA-DR restriction elements make the novel mHags possible targets for development of immunotherapeutic strategies.
Comprehensive assessment of T-cell receptor β-chain diversity in αβ T cells
Authors: Robins Harlan S. , Campregher Paulo V. , Srivastava Santosh K. , Wacher Abigail , Turtle Cameron J. , Kahsai Orsalem , Riddell Stanley R. , Warren Edus H. , Carlson Christopher S. 
Published: August 2009

AbstractThe adaptive immune system uses several strategies to generate a repertoire of T- and B-cell antigen receptors with sufficient diversity to recognize the universe of potential pathogens. In αβ T cells, which primarily recognize peptide antigens presented by major histocompatibility complex molecules, most of this receptor diversity is contained within the third complementarity-determining region (CDR3) of the T-cell receptor (TCR) α and β chains. Although it has been estimated that the adaptive immune system can generate up to 1016 distinct αβ pairs, direct assessment of TCR CDR3 diversity has not proved amenable to standard capillary electrophoresis-based DNA sequencing. We developed a novel experimental and computational approach to measure TCR CDR3 diversity based on single-molecule DNA sequencing, and used this approach to determine the CDR3 sequence in millions of rearranged TCRβ genes from T cells of 2 adults. We find that total TCRβ receptor diversity is at least 4-fold higher than previous estimates, and the diversity in the subset of CD45RO+ antigen-experienced αβ T cells is at least 10-fold higher than previous estimates. These methods should prove valuable for assessment of αβ T-cell repertoire diversity after hematopoietic cell transplantation, in states of congenital or acquired immunodeficiency, and during normal aging.
Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units
Authors: Verneris Michael R. , Brunstein Claudio G. , Barker Juliet , MacMillan Margaret L. , DeFor Todd , McKenna David H. , Burke Michael J. , Blazar Bruce R. , Miller Jeffrey S. , McGlave Philip B. , Weisdorf Daniel J. , Wagner John E. 
Published: August 2009

AbstractUmbilical cord blood (UCB) transplantation is potentially curative for acute leukemia. This analysis was performed to identify risk factors associated with leukemia relapse following myeloablative UCB transplantation. Acute leukemia patients (n = 177; 88 with acute lymphoblastic leukemia and 89 with acute myeloid leukemia) were treated at a single center. Patients received a UCB graft composed of either 1 (47%) or 2 (53%) partially human leukocyte antigen (HLA)–matched unit(s). Conditioning was with cyclophosphamide and total body irradiation with or without fludarabine. The incidence of relapse was 26% (95% confidence interval [CI], 19%-33%). In multivariate analysis, relapse was higher in advanced disease patients (≥ third complete remission [CR3]; relative risk [RR], 3.6; P < .01), with a trend toward less relapse in recipients of 2 UCB units (RR = 0.6; P = .07). However, relapse was lower for CR1-2 patients who received 2 UCB units (RR 0.5; P < .03). Leukemia-free survival was 40% (95% CI, 30%-51%) and 51% (95% CI, 41%-62%) for single- and double-unit recipients, respectively (P = .35). Although it is known that transplantation in CR1 and CR2 is associated with less relapse risk, this analysis reveals an enhanced graft-versus-leukemia effect in acute leukemia patients after transplantation with 2 partially HLA-matched UCB units. This trial was registered at http://clinicaltrials.gov as NCT00309842.
Comparative 454 pyrosequencing of transcripts from two olive genotypes during fruit development
Authors: Alagna Fiammetta , D'Agostino Nunzio , Torchia Laura , Servili Maurizio , Rao Rosa , Pietrella Marco , Giuliano Giovanni , Chiusano Maria Luisa , Baldoni Luciana , Perrotta Gaetano 
Published: August 2009

Abstract

Background
Despite its primary economic importance, genomic information on olive tree is still lacking. 454 pyrosequencing was used to enrich the very few sequence data currently available for the Olea europaea species and to identify genes involved in expression of fruit quality traits.

Results
Fruits of Coratina, a widely cultivated variety characterized by a very high phenolic content, and Tendellone, an oleuropein-lacking natural variant, were used as starting material for monitoring the transcriptome. Four different cDNA libraries were sequenced, respectively at the beginning and at the end of drupe development. A total of 261,485 reads were obtained, for an output of about 58 Mb. Raw sequence data were processed using a four step pipeline procedure and data were stored in a relational database with a web interface.

Conclusion
Massively parallel sequencing of different fruit cDNA collections has provided large scale information about the structure and putative function of gene transcripts accumulated during fruit development. Comparative transcript profiling allowed the identification of differentially expressed genes with potential relevance in regulating the fruit metabolism and phenolic content during ripening.