bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of CTGF and Cyr61 in colorectal cancer
Authors: Ladwa Rahul , Pringle Howard , Kumar Rohan , West Kevin 
Published: November 2010

BackgroundThe CCN genes encode secreted extracellular matrix proteins cysteine rich-61 (Cyr61), connective tissue growth factor (CTGF) and nephroblastoma overexpressed (Nov). They are involved in diverse cellular functions. Expression of these factors in tumours has produced conflicting results. More recently, research has focused on molecular biomarkers to indicate progression of a disease or the susceptibility of the disease to a given treatment.AimsThe purpose of this study was to determine the expression of CTGF and Cyr61 genes and proteins in colorectal cancer. Expression was compared with various clinicopathological parameters including Dukes' stage and TNM stage. We determined the in vitro effects of hypoxia on Cyr61 and CTGF expression in colorectal cancer cell lines.ResultsHypoxia significantly reduced CTGF mRNA expression (p<0.01) in HT29 and Caco-2 cell lines. Cyr61 was induced (p<0.01) in HT29 cell lines but significantly reduced (p<0.01) in Caco-2 cell lines under hypoxic conditions. High levels of CTGF and Cyr61 mRNA were found in colorectal cancer compared with normal colon (p<0.05). Expression was reduced in more advanced cancers (Dukes' C vs Dukes' A and B). There was a significant association between CTGF protein expression and advancing Dukes' stage (p<0.01), T stage (p<0.01) and lymph-node involvement (p<0.05), but there was no significant association between Cyr61 expression and clinicopathological parameters.ConclusionUpregulation of Cyr61 and CTGF gene expression in colorectal cancer suggests they have a role in tumour initiation or development. However, the genes are not as highly expressed in advanced stages of colorectal cancer, suggesting their role may be important at an early stage of tumour development. These genes maybe used as early biomarkers to risk-stratify patients. Hypoxia alters the expression of these genes in colorectal cancer cell lines. Further studies are needed to determine whether targeting these genes would be useful in future therapy.
Spatial and temporal influence of glaciers and rivers on the sedimentary environment in Sassenfjorden and Tempelfjorden, Spitsbergen
Authors: Forwick Matthias , Vorren Tore O. , Hald Morten , Korsun Sergei , Roh Yul , Vogt Christoph , Yoo Kyu-Cheul 
Published: November 2010

Abstract

Multiproxy analyses including hydrographical, geochemical, foraminferal, lithological and geophysical data reveal variable influences of the glaciers Tunabreen and von Postbreen as well as the river Sassenelva on the sedimentary environment in two Spitsbergen fjords during the Late Weichselian and the Holocene. Grounded ice covered the study area during the last glacial. The glacier fronts retreated stepwise during the latest Weichselian/earliest Holocene, and the glaciers were probably small during the early Holocene. A growth of Tunabreen occurred between 6 and 4 cal ka BP. Reduced input from Tunabreen from
c.
3.7 cal ka BP was probably a result of suppressed iceberg rafting related to the enhanced formation of sea ice and/or reduced meltwater runoff. During the past two millennia, the glacier fronts advanced and retreated several times. The maximum Holocene glacier extent was reached at the end of a surge of von Postbreen in AD 1870. Characteristics of the modern glaciomarine environment include: (1) different colours and bulk-mineral assemblages of the turbid waters emanating from the main sediment sources; (2) variable locations of the turbid-water plumes as a consequence of wind forcing and the Coriolis effect; (3) stratified water masses during summers with interannual variations; (4) increasing productivity with increasing distance from the glacier fronts; (5) foraminifera-faunal assemblages typical for glacierproximal settings; and (6) periodical mass-transport activity.
Paraglacial slope instability in Scottish fjords: examples from Little Loch Broom, NW Scotland
Authors: Stoker Martyn S. , Wilson Charles R. , Howe John A. , Bradwell Tom , Long David 
Published: November 2010

Abstract
Lateglacial–Holocene fjord sediments in Little Loch Broom preserve evidence of extensive slope instability. The major area of reworking is in the outer loch and mid-loch sill region where ice-contact/ice-proximal deposits of the Lateglacial Assynt Glaciogenic Formation have been disrupted by sliding and mass-flow processes linked to the Little Loch Broom Slide Complex and the adjacent Badcaul Slide. Mass failure was instigated about 14–13 ka BP, and is probably the response of the landscape to deglaciation immediately following the removal of ice support during glacial retreat. An initial phase of translational sliding was followed by rotational sliding, as revealed by the superimposition of scallop-shaped slumps on a larger-scale rectilinear pattern of failure. Paraglacial landscape readjustment may also have been enhanced by episodic seismic activity linked to glacio-isostatic unloading. In the inner fjord, evidence of Holocene mass failure includes the Ardessie debris lobe and a discrete intact slide block preserved within the postglacial basinal deposits. The former is a localized accumulation linked to a fluvial catchment on the adjacent An Teallach massif. These mass-transport deposits may represent an ongoing response to paraglacial processes, albeit much reduced (relative to the major slides) in terms of sediment supply to the fjord.
Variations in organic carbon flux and stagnation periods during the last 2400 years in a Skagerrak fjord basin, inferred from benthic foraminiferal δ
13
C
Authors: Filipsson Helena L. , Nordberg Kjell 
Published: November 2010

Abstract

A well-dated high-resolution δ
13
C record of the last 2400 a, based on the benthic foraminifer
Cassidulina laevigata
, is presented for Gullmar Fjord, Sweden. The time interval covers the Roman Warm Period (RWP), the Viking Age/Medieval Warm Period (VA/MWP), the Little Ice Age (LIA) and the most recent warming. There is little variation in the δ
13
C record until the early Viking Age (AD 800), when the δ
13
C signal becomes significantly more negative and continues to decrease throughout the VA/MWP. The δ
13
C signal increases both at the beginning and at the end of the LIA but is marked by more negative values during the larger part of the period. Since about 1970, the δ
13
C values are more negative than the long-term average. This general negativity of the record may result from a higher flux of organic matter, possibly of terrestrial origin due to land-use changes together with moderate changes in stagnation periods since the VA/MWP. In most recent times, the oceanic Suess effect together with increased number of extended stagnation periods are probably the main causes of the shift towards more negative δ
13
C values.
Scottish west coast fjords since the last glaciation: a review
Authors: Mcintyre Kate L. , Howe John A. 
Published: November 2010

Abstract

Evidence from seismic profiles, sidescan and multibeam sonar surveys and sediment cores reveal important information about the depositional history of Scotland's fjords during the last deglacial transition and the subsequent Holocene. Devensian glaciation removed pre-existing sediments both inside and outside the fjord basins, and deposited a diamict over much of the subsequent erosional surface. Glaciomarine sequences deposited during the initial retreat of this ice margin are mainly preserved in the sea area outside the fjords. Younger glaciomarine units present within the fjord basins are often attributed to the later Younger Dryas re-advance (12.8–11.5 ka BP). Younger Dryas ice reworked Devensian sediments, depositing terminal moraines at the mouths of a number of fjords and glaciomarine units within the basins during its retreat. Ice margins oscillated throughout deglaciation, although the latter stages of post-Younger Dryas retreat may have occurred rapidly with topographic pinning an important factor in determining the style of retreat. Holocene records from the fjords are limited, but tentatively support the onshore evidence for a tundra-style landscape in the earliest Holocene, followed by a warming of the climate and, latterly (
c
. 2000 ka BP), increasing humidity. In the more recent past, human activities such as deforestation, fishing, aquaculture and industry have been recorded in the fjord sediments.
Modern glacimarine processes and potential future behaviour of Kronebreen and Kongsvegen polythermal tidewater glaciers, Kongsfjorden, Svalbard
Authors: Trusel Luke D. , Powell R. D. , Cumpston R. M. , Brigham-Grette J. 
Published: November 2010

Abstract

Glacimarine dynamics and associated sedimentary processes are closely tied to glacial regime and reflect dominant climatic conditions. Quantitative measurements for subpolar glaciers, such as sediment yield, are limited especially near glacial termini where most sediment accumulates. Here we characterize the modern glacimarine environment, quantify sediment flux and yield, document landform genesis and hypothesize potential future behaviour of Kronebreen and Kongsvegen glaciers in inner Kongsfjorden, Svalbard. A minimum of 6.74×10
3
g m
−2
d
−1
(at least 300 mm a
−1
) of glacimarine sediment is building a grounding-line fan via submarine stream discharge from Kronebreen. Average daily sediment flux to the ice-contact basin is recorded to be 2.6×10
3
g m
−2
d
−1
or an average annual flux of 1.56×10
5
g m
−2
a
−1
. We measure an average annual ice-contact sediment yield of 1.20×10
4
tonnes km
−2
a
−1
associated with the rapid genesis of grounding-line landforms. With forecasted warming we expect meltwater volumes and sediment flux to increase. Grounding-line deposits may aggrade above water, tending to stabilize the terminus at least initially if the sediment is sufficient to counteract total terminus ablation. This would hold until either the glaciers next surge or climatic warming ablates the glaciers through surface melting.
The Ability to Form Primary Tumor Xenografts Is Predictive of Increased Risk of Disease Recurrence in Early-Stage Non–Small Cell Lung Cancer
Authors: John Thomas , Kohler Derek , Pintilie Melania , Yanagawa Naoki , Pham Nhu-An , Li Ming , Panchal Devang , Hui Frances , Meng Fannong , Shepherd Frances A. , Tsao Ming-Sound 
Published: November 2010

Abstract
Purpose: Primary tumor xenografts (PTXG) established directly from patients' primary tumors in immunosuppressed animals might represent the spectrum of histologic complexity of lung cancers better than xenografts derived from established cell lines. These models are important in the study of aberrant biological pathways in cancers and as preclinical models for testing new therapeutic agents. However, not all primary tumors engraft when implanted into immunosuppressed mice. We have investigated factors that may influence the ability of primary non–small cell lung cancer (NSCLC) to form xenografts and their association with clinical outcome.
Experimental Design: Tumor fragments from patients undergoing curative surgery were implanted into NOD-SCID (nonobese diabetic-severely combined immunodeficient) mice within 24 hours of surgery. Patient characteristics for tumors that engrafted (XG) and did not engraft (no-XG) were compared. Patient tumor DNA was profiled for the presence of 238 known mutations in 19 cancer-associated genes by using the MassARRAY platform.
Results: Xenografts were established and passaged successfully from 63 of 157 (40%) implanted NSCLCs. Tumor factors associated with engraftment included squamous histology, poor differentiation, and larger tumor size. Significantly fewer EGFR (epidermal growth factor receptor)-mutated tumors engrafted (P = 0.03); conversely, more K-RAS–mutated tumors engrafted (P = 0.05). In multivariate analysis including age, sex, stage, and mutation, patients with XG tumors had significantly shorter disease-free survival compared with no-XG patients (hazard ratio: 7.0, 95% CI: 3.1–15.81; P &lt; 0.000003).
Conclusion: PTXGs closely mirror the histology and molecular profiles of primary tumors and therefore may serve as important preclinical models. Tumors that engraft are biologically more aggressive and may be more representative of cancers with a higher propensity to relapse after surgery. Clin Cancer Res; 17(1); 134–41. ©2010 AACR.
Rectal laterally spreading tumors successfully treated in two steps by endoscopic submucosal dissection and endoscopic mucosal resection
Authors: Stroppa Italo , Milito Giovanni , Lionetti Raffaella , Palmieri Giovanni , Cadeddu Federica , Pallone Francesco 
Published: November 2010

Abstract

Background
Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy alternative to endoscopic mucosal resection (EMR) for superficial gastrointestinal neoplasms >2 cm. ESD allows for the direct dissection of the submucosa and large lesions can be resected en bloc. ESD is not limited by resection size, increases histologically complete resection rates and may reduce the local recurrence.
Nevertheless, the technique is time-consuming, technically demanding and associated with a high complication rate. To reduce the risk of complications, different devices and technical advances have been proposed with conflicting results and, still, ESD en bloc resections of huge lesions are associated with increased complications.

Case Presentation
We successfully used a combined ESD/EMR technique for huge rectal laterally spreading tumors (LSTs). ESD was used for circumferential resection of 2/3 of the lesion followed by piecemeal resection (2-3 pieces) of the central part of the tumour.
In all three patients we obtained the complete dissection of the polyp and the complete histological evaluation in absence of complications and recurrence at 6 months' follow up.

Conclusions
In the treatment of rectal LSTs, the combined treatment - ESD/EMR resection may be considered a suitable therapeutic option, indicated in selected cases as an alternative to surgery, in which the two techniques are neither reliable nor safe separately. However, to confirm our results, larger trials with longer follow up are required together with improvement of the technique and of the technical devices.
Association of serum markers with improvement in clinical response measures after treatment with golimumab in patients with active rheumatoid arthritis despite receiving methotrexate: results from the GO-FORWARD study
Authors: Visvanathan Sudha , Rahman Mahboob U , Keystone Edward , Genovese Mark , Klareskog Lars , Hsia Elizabeth , Mack Michael , Buchanan Jacqui , Elashoff Michael , Wagner Carrie 
Published: November 2010

Abstract
Introduction
The goal of this study was to identify serum markers that are modulated by treatment with golimumab with or without methotrexate (MTX) and are associated with clinical response.

Methods
Sera were collected at weeks 0 and 4 from a total of 336 patients (training dataset, n = 100; test dataset, n = 236) from the GO-FORWARD study of patients with active rheumatoid arthritis despite MTX. Patients were randomly assigned to receive placebo plus MTX; golimumab, 100 mg plus placebo; golimumab, 50 mg plus MTX; or golimumab, 100 mg plus MTX. Subcutaneous injections were administered every 4 weeks. Samples were tested for select inflammatory, bone, and cartilage markers and for protein profiling using multianalyte profiles.

Results
Treatment with golimumab with or without MTX resulted in significant decreases in a variety of serum proteins at week 4 as compared with placebo plus MTX. The American College of Rheumatology (ACR) 20, ACR 50, and Disease Activity Score (DAS) 28 responders showed a distinct biomarker profile compared with nonresponding patients.

Conclusions
ACR 20 and ACR 50 responders among the golimumab/golimumab + MTX-treated patients had a distinct change from baseline to week 4 in serum protein profile as compared with nonresponders. Some of these changed markers were also associated with multiple clinical response measures and improvement in outcome measures in golimumab/golimumab + MTX-treated patients. Although the positive and negative predictive values of the panel of markers were modest, they were stronger than C-reactive protein alone in predicting clinical response to golimumab.

Trial registration
http://ClinicalTrials.gov identification number: NCT00264550.
Von willebrand factor increases endothelial cell adhesiveness for human mesenchymal stem cells by activating p38 mitogen-activated protein kinase
Authors: Potapova Irina A , Cohen Ira S , Doronin Sergey V 
Published: November 2010

Abstract
Introduction
Delivered systemically or natively circulating mesenchymal stem cells accumulate in injured tissues. During homing mesenchymal stem cells adhere to endothelial cells and infiltrate underlying tissue. Previously we have shown that adhesiveness of endothelial cells for mesenchymal stem cells correlates with the inhibition of mitochondrial function of endothelial cells and secretion of von Willebrand factor. We hypothesized that von Willebrand factor is an auto/paracrine regulator of endothelial cell adhesiveness and studied the effect of von Willebrand factor on adhesion of mesenchymal stem cells to endothelial cells.

Methods
We used Affymetrix DNA microarrays, human protein phospho-MAPK array, Western blot, cell-based ELISA and flow cytometry analysis to study the activation of endothelial cells by von Willebrand factor. Cell adhesion assay and protein kinase inhibitors were used to evaluate the role of mitogen-activated protein kinases in the regulation of endothelial cell adhesiveness for mesenchymal stem cell.

Results
Treatment of endothelial cells with von Willebrand factor stimulated the mesenchymal stem cell adhesion in a time- and concentration-dependent manner. Mesenchymal stem cells did not adhere to immobilized von Willebrand factor and did not express receptors for von Willebrand factor suggesting that the stimulation of the mesenchymal stem cell adhesion is a result of endothelial cell activation with von Willebrand factor. Treatment of endothelial cells with von Willebrand factor activated ERK-1,2 and p38 MAPK without an effect on gene or cell surface expression of E-selectin, P-selectin, VCAM1 and ICAM1. Inhibition of p38 MAPK, but not ERK-1,2, in endothelial cells completely abrogated the stimulation of the mesenchymal stem cell adhesion by von Willebrand factor.

Conclusions
Von Willebrand factor is an auto/paracrine regulator of endothelial cells. Activation of p38 MAPK in endothelial cells by von Willebrand factor is responsible for the regulation of endothelial cell adhesiveness for mesenchymal stem cells.
Identification and Functional Analysis of Novel Human Growth Hormone Secretagogue Receptor (GHSR) Gene Mutations in Japanese Subjects with Short Stature
Authors: Inoue Hiroshi , Kangawa Natsumi , Kinouchi Atsuko , Sakamoto Yukiko , Kimura Chizuko , Horikawa Reiko , Shigematsu Yosuke , Itakura Mitsuo , Ogata Tsutomu , Fujieda Kenji ,   on behalf of the Japan Growth Genome Consortium
Published: November 2010

abstract

Context:
Short stature (SS) is a multifactorial developmental condition with a significant genetic component. Recent studies have revealed that rare deleterious mutations in the GH-secretagogue receptor type 1A (GHSR1A) gene could be a cause of familial SS or GH deficiency.

Objective:
The aim of this study was to evaluate the contribution of GHSR1A mutations to the molecular mechanism underlying SS in Japanese subjects.

Methods:
We performed mutational screening of the GHSR1A gene in 127 unrelated Japanese SS patients diagnosed with either isolated GH deficiency or idiopathic SS. Identified mutations were analyzed in 188 control subjects, and their functional properties were examined in a heterologous expression system.

Results:
Four novel heterozygous GHSR1A mutations were identified (ΔQ36, P108L, C173R, and D246A). Expression studies demonstrated that these mutations had varying functional consequences: 1) all mutations showed a loss-of-function effect on the constitutive signaling activity of GHSR1A, but the degree of loss varied widely; 2) C173R caused intracellular retention of the mutated protein, resulting in total loss of receptor function; 3) P108L resulted in a large decrease in binding affinity to ghrelin, without affecting its surface expression; 4) D246A uniquely impaired agonist- and inverse agonist-stimulated receptor signaling; and 5) ΔQ36 showed only a subtle reduction in constitutive activity. The cumulative frequency of these putative functional mutations was significantly higher in the patient group than in controls (4.72 vs. 0.53%; P = 0.019; odds ratio = 9.28; 95% confidence interval, 1.10–78.0).

Conclusions:
Our results suggest that GHSR1A mutations contribute to the genetic etiology of SS in the Japanese population.
Belimumab: A BLyS-Specific Inhibitor for Systemic Lupus Erythematosus
Authors: Wiglesworth Amy K , Ennis Kelly M , Kockler Denise R 
Published: November 2010

Objective: To review the efficacy, safety, dosing, drug interactions, as well as economic and therapeutic considerations of belimumab, an investigational B-lymphocyte stimulator (BLyS) inhibitor. Data Sources: A systematic, English-language MEDLINE search (1966-August 2010) was conducted using the search terms belimumab, Benlysta, B-lymphocyte stimulators, BLyS-specific inhibitors, and systemic lupus erythematosus (SLE). Press releases and bibliographies were reviewed for additional information and citations. Study Selection and Data Extraction: Belimumab was first identified and studied as a human protein target in 1999. Therefore, all published clinical trials and abstracts evaluating the safety and efficacy of belimumab for treatment of SLE as well as review articles from 1999 to present were evaluated for inclusion. Additional data were extracted from the manufacturer's Web site and Food and Drug Administration (FDA) documents. Data Synthesis: Current therapies for SLE target nonspecific sites for inflammatory reduction and immune system suppression. Belimumab is a target-specific, human lgG1λ monoclonal B-lymphocyte stimulator inhibitor currently in late stage investigation for the treatment of SLE. Unpublished Phase 3 trials have reported statistically significant results for primary endpoints when belimumab 10 mg/kg plus standard of care was compared to placebo plus standard of care in seropositive patients with SLE. Overall, belimumab has been relatively well tolerated with discontinuation rates and adverse events similar to those of placebo. If belimumab is approved by the FDA, its US market launch would be expected in 2011. Conclusions: Belimumab has shown significant benefits for patients with SLE in the few Phase 3 trials that have been published. However, questions remain regarding optimal patient population, duration of treatment, place in therapy, and long-term adverse effects.
Lithium-Transition Metal-Tetrelides – Structure and Lithium Mobility
Authors: Pöttgen Rainer , Dinges Tim , Eckert Hellmut , Sreeraj Puravankara , Wiemhöfer Hans-Dieter 
Published: November 2010

Abstract
Lithium-transition metal (T)-tetrelides (tetr.= C, Si, Ge, Sn, Pb) are an interesting class of materials with greatly differing crystal structures. The transition metal and tetrel atoms build up covalently bonded networks which leave cavities or channels for the lithium atoms. Depending on the bonding of the lithium atoms to the polyanionic network one observes mobility of the lithium atoms. The crystal chemistry, chemical bonding, 7Li solid state NMR, and the electrochemical behavior of the tetrelides are reviewed herein.