bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Factor-κB Is Central to the Expression of Truncated Neurokinin-1 Receptor in Breast Cancer: Implication for Breast Cancer Cell Quiescence within Bone Marrow Stroma
Authors: Ramkissoon Shakti H. , Patel Prem S. , Taborga Marcelo , Rameshwar Pranela 
Published: February 2007

Abstract
Breast cancer is a leading cause of mortality among women in the United States. Tac1 and neurokinin-1 (NK1) are involved in autocrine stimulation of breast cancer cells (BCCs). The single NK1 gene produces full-length (NK1-FL) and truncated (NK1-Tr) forms. NK1-Tr mediates malignancy in breast cells. We now report a critical role for nuclear factor-κB (NF-κB) in the expression of NK1-Tr, but not NK1-FL, in human BCCs. By Western and Northern blot analyses, NK1-FL and NK1-Tr were coexpressed in BCCs but were undetectable in nontumorigenic cells. Loss of repressive activity within the 5′ flanking region of the NK1 partly accounts for constitutive expression of NK1 in BCCs but could not account for the presence of NK1-Tr. Transient transfections with dominant-negative and wild-type IκB show that activation of NF-κB is required for the expression of NK1-Tr. Tac1 gene was linked to the generation of NK1-Tr because its overexpression in BCCs led to the production of multiple cytokines that can activate NF-κB to mediate NK1-Tr expression. Studies with Tac1 knockdown BCCs and Tac1-expressing nontumorigenic breast cells verified a role for NF-κB in the expression of NK1-Tr. The quiescent phenotype of BCCs on contact with bone marrow stroma was partly explained by decreased NF-κB activation and undetectable NK1-Tr. In summary, this study shows a role for NF-κB in the expression of NK1-Tr in BCCs, which seems to be reversed by bone marrow stromal cells. [Cancer Res 2007;67(4):1653–9]
Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling
Authors: Nahta Rita , Yuan Linda X.H. , Du Yi , Esteva Francisco J. 
Published: February 2007

AbstractThe majority of breast cancer patients who achieve an initial therapeutic response to the HER2-targeted antibody trastuzumab will show disease progression within 1 year. Thus, the identification of novel agents that effectively inhibit survival of cancer cells that have progressed on trastuzumab is critical. In the current study, we show that the dual epidermal growth factor receptor (EGFR)/human EGFR-2 (HER2) kinase inhibitor lapatinib induces apoptosis in trastuzumab-resistant cells derived from the HER2-overexpressing SKBR3 breast cancer line. Lapatinib inhibited EGFR and HER2 signaling in resistant cells, blocking activation of downstream Akt, mitogen-activated protein kinase, and S6 kinases and inducing expression of p27kip1. Importantly, lapatinib also inhibited insulin-like growth factor I (IGF-I) signaling and growth-promoting effects in parental and resistant cells, and the cytotoxic effects of lapatinib were further enhanced by the IGF-I receptor–blocking antibody αIR3. As increased IGF-I receptor signaling has been implicated in trastuzumab resistance, our data strongly support further study of lapatinib as a potential therapeutic in breast cancers that have progressed on trastuzumab. [Mol Cancer Ther 2007;6(2):667–74]
Potent cytotoxicity of the phosphatase inhibitor microcystin LR and microcystin analogues in OATP1B1- and OATP1B3-expressing HeLa cells
Authors: Monks Noel R. , Liu Shuqian , Xu Yongsheng , Yu Hui , Bendelow Adam S. , Moscow Jeffrey A. 
Published: February 2007

Abstract
Microcystins are a family of cyclic peptides that are potent inhibitors of the protein phosphatase families PP1 and PP2A. Only three human proteins are thought to be able to mediate the hepatic uptake of microcystins (the organic anion-transporting polypeptides OATP1B1, OATP1B3, and OATP1A2), and the predominant hepatic expression of these transporters accounts for the liver-specific toxicity of microcystins. A significant obstacle in the study of microcystins as anticancer drugs is the requirement of specific transport proteins for cellular uptake. We report that OATP1B3 mRNA is up-regulated in non–small cell lung cancer tumors in comparison with normal control tissues. This finding led to the exploration of microcystins as potential anticancer agents. We have developed a HeLa cell model with functional OATP1B1 and OATP1B3 activity. Transiently transfected HeLa cells are over 1,000-fold more sensitive to microcystin LR than the vector-transfected control cells, showing that transporter expression imparts marked selectivity for microcystin cytotoxicity. In addition, microcystin analogues showed variable cytotoxicities in the OATP1B1- and OATP1B3-transfected cells, including two analogues with IC50 values &lt;1 nmol/L. Cytotoxicity of microcystin analogues seems to correlate to the inhibition of PP2A in these cells and induces rapid cell death as seen by chromatin condensation and cell fragmentation. These studies show that microcystin-induced phosphatase inhibition results in potent cytotoxicity when microcystin compounds can gain intracellular access and are a potent novel class of therapeutic agents for tumors expressing these uptake proteins. [Mol Cancer Ther 2007;6(2):587–98]
Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit
Authors: Williams Kaye J. , Telfer Brian A. , Shannon Aoife M. , Babur Muhammad , Stratford Ian J. , Wedge Stephen R. 
Published: February 2007

Abstract
AZD2171 is a highly potent, orally active inhibitor of vascular endothelial growth factor receptor signaling. The potential for AZD2171 to enhance the antitumor effects of radiotherapy was investigated in lung (Calu-6) and colon (LoVo) human tumor xenograft models. Combined treatment resulted in a significantly enhanced growth delay compared with either modality alone. The enhancement was independent of whether chronic once daily AZD2171 treatment was given 2 h prior to each radiation fraction (2 Gy daily for 3 or 5 consecutive days), and daily thereafter, or commenced immediately following the course of radiotherapy. Histologic assessments revealed that 5 days of radiation (2 Gy) or AZD2171 (3 or 6 mg/kg/d) reduced vessel density and perfusion. Concomitant AZD2171 and radiation enhanced this effect and produced a significant increase in tumor hypoxia. Concomitant AZD2171 (6 mg/kg/d) was also found to reduce tumor growth significantly during the course of radiotherapy (5 × 2 Gy). However, the extent and duration of tumor regression observed postradiotherapy was similar to sequentially treated tumors, suggesting that preirradiated tumors were sensitized to AZD2171 treatment. An enhanced antivascular effect of administering AZD2171 postradiotherapy was observed in real-time in Calu-6 tumors grown in dorsal window chambers. Collectively, these data support the clinical development of AZD2171 in combination with radiotherapy. [Mol Cancer Ther 2007;6(2):599–606]
Turning on Default Reasons
Authors: McKeever Sean , Ridge Michael 
Published: February 2007

AbstractParticularism takes an extremely ecumenical view of what considerations might count as reasons and thereby threatens to ‘flatten the moral landscape’ by making it seem that there is no deep difference between, for example, pain, and shoelace color. After all, particularists have claimed, either could provide a reason provided a suitable moral context. To avoid this result, some particularists draw a distinction between default and non-default reasons. The present paper argues that all but the most deflationary ways of drawing this distinction are either implausible or else insufficient to help the particularist avoid flattening the moral landscape. The difficulty can be avoided, however, if we reject particularism's extremely ecumenical view of reasons.
The Structure of Empathy
Authors: Deonna Julien 
Published: February 2007

AbstractIf Sam empathizes with Maria, then it is true of Sam that (1) Sam is aware of Maria's emotion, and (2) Sam ‘feels in tune’ with Maria. On what I call thetransparency conception of how they interact when instantiated, I argue that these two conditions are collectively necessary and sufficient for empathy. I first clarify the ‘awareness’ and ‘feeling in tune’ conditions, and go on to examine different candidate models that explain the manner in which these two conditions might come to be concomitantly instantiated in a subject. I dismiss what I call theparallel and oscillation models for not satisfying the transparency condition, i.e. for failing to capture that, if Sam empathizes with Maria, then Sam's own emotional experience towards the object of Maria's emotion has to be mediated by Maria's own emotional experience. I conclude in favour the fusion model as the only model capable of satisfying the transparency condition, and I argue that the suggested proposal illuminates the difference between it and other ways in which we understand the emotions of others. Finally, I expand and clarify the conception of empathy as transparency through responses to obvious objections that the view raises.
Moderation of the platelet releasate response by aspirin
Authors: Coppinger Judith A. , O'Connor Roisin , Wynne Kieran , Flanagan Michelle , Sullivan Matthew , Maguire Patricia B. , Fitzgerald Desmond J. , Cagney Gerard 
Published: February 2007

AbstractModulation of the proteins released during activation is one mechanism whereby aspirin may influence platelet-mediated human disease. We investigated the effect of aspirin on the platelet releasate using mass spectrometry and found that different agonists evoked different releasate profiles, with aspirin having a general moderating effect on the amount of protein released regardless of the agonist. These observations were confirmed for several cytokines using an antibody array approach.
Geographical variation in radiological services: a nationwide survey
Authors: Lysdahl Kristin Bakke , Børretzen Ingelin 
Published: February 2007

Abstract
Background
Geographical variation in health care services challenges the basic principle of fair allocation of health care resources. This study aimed to investigate geographical variation in the use of X-ray, CT, MRI and Ultrasound examinations in Norway, the contribution from public and private institutions, and the impact of accessibility and socioeconomic factors on variation in examination rates.

Methods
A nationwide survey of activity in all radiological institutions for the year 2002 was used to compare the rates per thousand of examinations in the counties. The data format was files/printouts where the examinations were recorded according to a code system.

Results
Overall rates per thousand of radiological examinations varied by a factor of 2.4. The use of MRI varied from 170 to 2, and CT from 216 to 56 examinations per 1000 inhabitants. Single MRI examinations (knee, cervical spine and head/brain) ranged high in variation, as did certain other spine examinations. For examination of specific organs, the counties' use of one modality was positively correlated with the use of other modalities. Private institutions accounted for 28% of all examinations, and tended towards performing a higher proportion of single examinations with high variability. Indicators of accessibility correlated positively to variation in examination rates, partly due to the figures from the county of Oslo. Correlations between examination rates and socioeconomic factors were also highly influenced by the figures from this county.

Conclusion
The counties use of radiological services varied substantially, especially CT and MRI examinations. A likely cause of the variation is differences in accessibility. The coexistence of public and private institutions may be a source of variability, along with socioeconomic factors. The findings represent a challenge to the objective of equality in access to health care services, and indicate a potential for better allocation of overall health care resources.

Previous publication
The data applied in this article was originally published in Norwegian in: Børretzen I, Lysdahl KB, Olerud HM: Radiologi i Noreg – undersøkingsfrekvens per 2002, tidstrendar, geografisk variasjon og befolkningsdose. StrålevernRapport 2006:6. Østerås: The Norwegian Radiation Protection Authority. The Norwegian Radiation Protection Authority has given the authors permission to republish the data.
Managed care and patient ratings of the quality of specialty care among patients with pain or depressive symptoms
Authors: Grembowski David , Paschane David , Diehr Paula , Katon Wayne , Martin Diane , Patrick Donald L 
Published: February 2007

Abstract
Background
Managed care efforts to regulate access to specialists and reduce costs may lower quality of care. Few studies have examined whether managed care is associated with patient perceptions of the quality of care provided by physician and non-physician specialists. Aim is to determine whether associations exist between managed care controls and patient ratings of the quality of specialty care among primary care patients with pain and depressive symptoms who received specialty care for those conditions.

Methods
A prospective cohort study design was conducted in the offices of 261 primary physicians in private practice in Seattle in 1997. Patients (N = 17,187) were screened in waiting rooms, yielding a sample of 1,514 patients with pain only, 575 patients with depressive symptoms only, and 761 patients with pain and depressive symptoms. Patients (n = 1,995) completed a 6-month follow-up survey. Of these, 691 patients received specialty care for pain, and 356 patients saw mental health specialists. For each patient, managed care was measured by the intensity of managed care controls in the patient's health plan and primary care office. Quality of specialty care at follow-up was measured by patient rating of care provided by the specialists. Outcomes were pain interference and bothersomeness, Symptom Checklist for Depression, and restricted activity days.

Results
The intensity of managed care controls in health plans and primary care offices was generally not associated with patient ratings of the quality of specialty care. However, pain patients in more-managed primary care offices had lower ratings of the quality of specialty care from physician specialists and ancillary providers.

Conclusion
For primary care patients with pain or depressive symptoms and who see specialists, managed care controls may influence ratings of specialty care for patients with pain but not patients with depressive symptoms.
Applying the compound Poisson process model to the reporting of injury-related mortality rates
Authors: Kegler Scott R 
Published: February 2007

AbstractInjury-related mortality rate estimates are often analyzed under the assumption that case counts follow a Poisson distribution. Certain types of injury incidents occasionally involve multiple fatalities, however, resulting in dependencies between cases that are not reflected in the simple Poisson model and which can affect even basic statistical analyses. This paper explores the compound Poisson process model as an alternative, emphasizing adjustments to some commonly used interval estimators for population-based rates and rate ratios. The adjusted estimators involve relatively simple closed-form computations, which in the absence of multiple-case incidents reduce to familiar estimators based on the simpler Poisson model. Summary data from the National Violent Death Reporting System are referenced in several examples demonstrating application of the proposed methodology.
An evaluation of LSU rDNA D1-D2 sequences for their use in species identification
Authors: Sonnenberg Rainer , Nolte Arne W , Tautz Diethard 
Published: February 2007

Abstract

Background
Identification of species via DNA sequences is the basis for DNA taxonomy and DNA barcoding. Currently there is a strong focus on using a mitochondrial marker for this purpose, in particular a fragment from the cytochrome oxidase I gene (COI). While there is ample evidence that this marker is indeed suitable across a broad taxonomic range to delineate species, it has also become clear that a complementation by a nuclear marker system could be advantageous. Ribosomal RNA genes could be suitable for this purpose, because of their global occurrence and the possibility to design universal primers. However, it has so far been assumed that these genes are too highly conserved to allow resolution at, or even beyond the species level. On the other hand, it is known that ribosomal gene regions harbour also highly divergent parts. We explore here the information content of two adjacent divergence regions of the large subunit ribosomal gene, the D1-D2 region.

Results
Universal primers were designed to amplify the D1-D2 region from all metazoa. We show that amplification products in the size between 800–1300 bp can be obtained across a broad range of animal taxa, provided some optimizations of the PCR procedure are implemented. Although the ribosomal genes occur in multiple copies in the genomes, we find generally very little intra-individual polymorphism (<< 0.1% on average) indicating that concerted evolution is very effective in most cases. Studies in two fish taxa (genus Cottus and genus Aphyosemion) show that the D1-D2 LSU sequence can resolve even very closely related species with the same fidelity as COI sequences. In one case we can even show that a mitochondrial transfer must have occurred, since the nuclear sequence confirms the taxonomic assignment, while the mitochondrial sequence would have led to the wrong classification. We have further explored whether hybrids between species can be detected with the nuclear sequence and we show for a test case of natural hybrids among cyprinid fish species (Alburnus alburnus and Rutilus rutilus) that this is indeed possible.

Conclusion
The D1-D2 LSU region is a suitable marker region for applications in DNA based species identification and should be considered to be routinely used as a marker complementing broad scale studies based on mitochondrial markers.
A pragmatic cluster randomised controlled trial of a Diabetes REcall And Management system: the DREAM trial
Authors: Eccles Martin P , Whitty Paula M , Speed Chris , Steen Ian N , Vanoli Alessandra , Hawthorne Gillian C , Grimshaw Jeremy M , Wood Linda J , McDowell David 
Published: February 2007

Abstract

Background
Following the introduction of a computerised diabetes register in part of the northeast of England, care initially improved but then plateaued. We therefore enhanced the existing diabetes register to address these problems. The aim of the trial was to evaluate the effectiveness and efficiency of an area wide 'extended,' computerised diabetes register incorporating a full structured recall and management system, including individualised patient management prompts to primary care clinicians based on locally-adapted, evidence-based guidelines.

Methods
The study design was a pragmatic, cluster randomised controlled trial, with the general practice as the unit of randomisation. Set in 58 general practices in three Primary Care Trusts in the northeast of England, the study outcomes were the clinical process and outcome variables held on the diabetes register, patient-reported outcomes, and service and patient costs. The effect of the intervention was estimated using generalised linear models with an appropriate error structure. To allow for the clustering of patients within practices, population averaged models were estimated using generalized estimating equations.

Results
Patients in intervention practices were more likely to have at least one diabetes appointment recorded (OR 2.00, 95% CI 1.02, 3.91), to have a recording of a foot check (OR 1.87, 95% CI 1.09, 3.21), have a recording of receiving dietary advice (OR 2.77, 95% CI 1.22, 6.29), and have a recording of blood pressure (BP) (OR 2.14, 95% CI 1.06, 4.36). There was no difference in mean HbA1c or BP levels, but the mean cholesterol level in patients from intervention practices was significantly lower (-0.15 mmol/l, 95% CI -0.25, -0.06). There were no differences in patient-reported outcomes or in patient-reported use of drugs, or uptake of health services. The average cost per patient was not significantly different between the intervention and control groups. Costs incurred in administering the system at the register and in general practice were in addition to these.

Conclusion
This study has shown benefits from an area-wide, computerised diabetes register incorporating a full structured recall and individualised patient management system. However, these benefits were achieved at a cost. In future, these costs may fall as electronic data exchange becomes a reliable reality.

Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN) Register, ISRCTN32042030.
Oestrogen receptor negative breast cancers exhibit high cytokine content
Authors: Chavey Carine , Bibeau Frédéric , Gourgou-Bourgade Sophie , Burlinchon Sandrine , Boissière Florence , Laune Daniel , Roques Sylvie , Lazennec Gwendal 
Published: February 2007

Abstract
Introduction
An emerging hypothesis suggests that cytokines could play an important role in cancer as potential modulators of angiogenesis and leucocyte infiltration.

Methods
A novel multiplexed flow cytometry technology was used to measure the expression of 17 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 [p70], IL-13, IL-17, granulocyte colony-stimulating factor [CSF], granulocyte-macrophage CSF, IFN-γ, monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1β, tumour necrosis factor [TNF]-α) at the protein level in 105 breast carcinoma. B lymphocyte, T lymphocyte and macrophage levels were determined by immunohistochemistry.

Results
Fourteen of the 17 cytokines were expressed in breast carcinoma, whereas only nine cytokines could be detected in normal breast. Most cytokines were more abundant in breast carcinoma than in normal breast, with IL-6, IL-8, granulocyte CSF, IFN-γ, MCP-1 and MIP-1β being very abundant. IL-2, IL-6, IL-8, IL-10, IFN-γ, MCP-1, MIP-1β and TNF-α, and to a lesser extent IL-1β and IL-13 exhibited levels of expression that were inversely correlated to oestrogen receptor and progesterone receptor status. Most cytokines were not correlated with age at cancer diagnosis, tumour size, histological type, or lymph node status. However, IL-1β, IL-6, IL-8, IL-10, IL-12, MCP-1 and MIP-1β were more abundant in high-grade tumours than in low-grade tumours. In addition, IL-8 and MIP-1β were expressed to a greater degree in HER2-positive than in HER2-negative patients. The expression of most of the studied cytokines was correlated to levels of activator protein-1, which is known to regulate numerous cytokines. Overexpression of MCP-1 and MIP-1β were linked to B lymphocyte, T lymphocyte and macrophage infiltration, whereas high levels of IL-8 were correlated with high macrophage content in tumour. Moreover, IL-8 positive tumours exhibited increased vascularization.

Conclusion
We found that multiple cytokines were overexpressed in oestrogen receptor negative breast carcinoma, and that the three major cytokines – MCP-1, MIP-1β and IL-8 – were correlated with inflammatory cell component, which could account for the aggressiveness of these tumours.