bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the Heat Shock Factor 1 by RNA Interference: A Potent Tool to Enhance Hyperthermochemotherapy Efficacy in Cervical Cancer
Authors: Rossi Antonio , Ciafrè Stefania , Balsamo Mirna , Pierimarchi Pasquale , Santoro M. Gabriella 
Published: August 2006

Abstract
Carcinoma of the uterine cervix is one of the highest causes of mortality in female cancer patients worldwide, and improved treatment options for this type of malignancy are highly needed. Local hyperthermia has been successfully used in combination with systemic administration of cisplatin-based chemotherapy in phase I/II clinical studies. Heat-induced expression of cytoprotective and antiapoptotic heat shock proteins (HSP) is a known complication of hyperthermia, resulting in thermotolerance and chemoresistance and hindering the efficacy of the combination therapy. Heat shock transcription factor 1 (HSF1) is the master regulator of heat-induced HSP expression. In the present report, we used small interfering RNA (siRNA) to silence HSF1 and to examine the effect of HSF1 loss of function on the response to hyperthermia and cisplatin-based chemotherapy in HeLa cervical carcinoma. We have identified the 322-nucleotide to 340-nucleotide HSF1 sequence as an ideal target for siRNA-mediated HSF1 silencing, have created a pSUPER-HSF1 vector able to potently suppress the HSF1 gene, and have generated for the first time human cancer cell lines with stable loss of HSF1 function. We report that, although it surprisingly does not affect cancer cell sensitivity to cisplatin or elevated temperatures up to 43°C when administered separately, loss of HSF1 function causes a dramatic increase in sensitivity to hyperthermochemotherapy, leading to massive (&gt;95%) apoptosis of cancer cells. These findings indicate that disruption of HSF1-induced cytoprotection during hyperthermochemotherapy may represent a powerful strategy to selectively amplify the damage in cancer cells and identify HSF1 as a promising therapeutic target in cervical carcinoma. (Cancer Res 2006; 66(15): 7678-85)
Vaccination Strategy Determines the Emergence and Dominance of CD8+ T-Cell Epitopes in a FVB/N Rat HER-2/neuMouse Model of Breast Cancer
Authors: Singh Reshma , Paterson Yvonne 
Published: August 2006

AbstractThe HER-2/neu oncogene has &gt;25 HLA epitopes, yet only one FVB/N mouse CD8+ T-cell epitope has been mapped to date. This epitope has been termed the immunodominant epitope for the FVB/N mouse, but we propose that the vaccination strategy determines the dominance of epitopes. Using a series of overlapping peptides, we have mapped another CD8+ T-cell epitope that emerges in the FVB/N mouse following vaccination with Listeria monocytogenes–based vaccines that express fragments of HER-2/neu. Following the identification of this novel H-2Kq-restricted epitope, we sought to compare the T-cell response to this epitope with the previously identified PDSLRDLSVF epitope. This newly identified epitope and the previously identified epitope lie within fragments contained in different vaccines, the PDSLRDLSVF epitope in Lm-LLO-EC2 and the newly identified PYNYLSTEV epitope in Lm-LLO-EC1; thus, it has been possible to compare the responses of these epitopes independent of any competing response between the epitopes. CTL analysis of individual peptide-pulsed target cells and intracellular cytokine stain for IFN-γ produced by splenocytes from Lm-LLO-EC1 compared with Lm-LLO-EC2 vaccinated FVB/N mice shows that there is no difference between the responses generated to either of these epitopes. We also show that the avidity of the CD8+ T cells for either of these epitopes is similar based on the concentration of peptide necessary to mediate similar levels of lysis of target cells. In addition, HER-2/neu DNA vaccination followed by CTL analysis further showed that both of these peptides can emerge as epitopes. (Cancer Res 2006; 66(15): 7748-57)
Antagonism of CXCR3 Inhibits Lung Metastasis in a Murine Model of Metastatic Breast Cancer
Authors: Walser Tonya C. , Rifat Salah , Ma Xinrong , Kundu Namita , Ward Chris , Goloubeva Olga , Johnson Michael G. , Medina Julio C. , Collins Tassie L. , Fulton Amy M. 
Published: August 2006

Abstract
Tumor cells aberrantly express chemokines and/or chemokine receptors, and some may promote tumor growth and metastasis. We examined the expression and function of chemokine receptor CXCR3 in a syngeneic murine model of metastatic breast cancer. By flow cytometry, CXCR3 was detected in all murine mammary tumor cell lines examined. All human breast cancer cell lines examined also expressed CXCR3, as did the immortalized but nontumorigenic MCF-10A cell line. Interaction of CXCR3 ligands, CXCL9, CXCL10, and CXCL11, with CXCR3 on the highly malignant murine mammary tumor cell line 66.1 resulted in intracellular calcium mobilization and chemotaxis in vitro. To test the hypothesis that tumor metastasis is facilitated by CXCR3 expressed by tumor cells, we employed a small molecular weight antagonist of CXCR3, AMG487. 66.1 tumor cells were pretreated with AMG487 prior to i.v. injection into immune-competent female mice. Antagonism of CXCR3 on 66.1 tumor cells inhibited experimental lung metastasis, and this antimetastatic activity was compromised in mice depleted of natural killer cells. Systemic administration of AMG487 also inhibited experimental lung metastasis. In contrast to the antimetastatic effect of AMG487, local growth of 66.1 mammary tumors was not affected by receptor antagonism. These studies indicate that murine mammary tumor cells express CXCR3 which facilitates the development of lung metastases. These studies also indicate for the first time that a small molecular weight antagonist of CXCR3 has the potential to inhibit tumor metastasis. (Cancer Res 2006; 66(15): 7701-7)
Notch1-Induced Transformation of RKE-1 Cells Requires Up-regulation of Cyclin D1
Authors: Stahl Mark , Ge Changhui , Shi Shaolin , Pestell Richard G. , Stanley Pamela 
Published: August 2006

Abstract
RKE-1 cells induced to overexpress activated Notch1 (RKE-ER-Nic) exhibit increased cyclin D1 transcripts and become transformed. However, the oncogenic pathway of Notch1-induced transformation is not known. Here, we use mutational analysis to functionally identify the sole region of the cyclin D1 promoter that responds to activated Notch1. The same region responds to activated Notch4 as well as to physiologic Notch ligand-induced Notch receptor signaling. The cyclin D1 gene was subsequently found to be a physiologic target of Notch signaling in Pofut1−/− mouse embryos defective in canonical Notch signaling and in embryos with an inactivating mutation in Notch1. To determine if Notch1-induced cyclin D1 expression in RKE-ER-Nic cells plays a direct role in transformation, cyclin D1 up-regulation was inhibited using a cyclin D1 antisense cDNA. We report here that transformation of RKE-ER-Nic cells is dependent on increased expression of cyclin D1 protein, which represents a new mechanism of Notch1-induced transformation. (Cancer Res 2006; 66(15): 7562-70)
A Cascade of Modules of a Network Defines Cancer Progression
Authors: Thiagalingam Sam 
Published: August 2006

Abstract
Similar histologic subtypes of cancers often exhibit different spectrum of genetic and epigenetic alterations. The heterogeneity observed due to lack of consistent and defined alterations affecting a unique set of gene(s) or gene products in cancers derived from a specific tissue, or an organ, pose a challenge in unraveling the molecular basis of the disease. This dilemma also complicates diagnosis, prognosis, effective management, and treatment modalities. To streamline the available and emerging data into a coherent scheme of events, a multimodular molecular network (MMMN) cancer progression model is presented as a roadmap to dissect the complexity inherent to this disease. The fact that disruption/dysregulation of more than one alternate target gene could affect the functionality of each specific module of a cascade provides a molecular basis for genetic and epigenetic heterogeneity in any given cancer. Polymorphisms/mutations as well as the extracellular matrix and or the epigenetically/genetically conditioned surrounding stromal cells could also influence the rate of tumorigenesis and the properties of the tumor cells. The formulation of MMMN cancer progression models for specific cancers is likely to provide the blueprints for the markers and targets to aid diagnosis, prevention, and therapy of this deadly disease. (Cancer Res 2006; 66(15): 7379-85)
Epidermal Growth Factor Receptor–Related Protein Inhibits Cell Growth and Invasion in Pancreatic Cancer
Authors: Wang Zhiwei , Sengupta Radha , Banerjee Sanjeev , Li Yiwei , Zhang Yuxiang , Rahman K.M. Wahidur , Aboukameel Amro , Mohammad Ramzi , Majumdar Adhip P.N. , Abbruzzese James L. , Sarkar Fazlul H. 
Published: August 2006

Abstract
The epidermal growth factor receptor (EGFR) signaling network plays critical roles in human cancers, including pancreatic cancer, suggesting that the discovery of specific agents targeting EGFR would be extremely valuable for pancreatic cancer therapy. EGFR-related protein (ERRP), a recently identified pan-erbB inhibitor, has been shown to inhibit growth and induce apoptosis of pancreatic cancer cells in vitro and tumor growth in a xenograft model. However, the precise molecular mechanism(s) by which ERRP exerts its antitumor activity remains unclear. The current investigation was undertaken to delineate the tumor growth inhibitory mechanism(s) of ERRP in pancreatic cancer cells. Using multiple molecular assays, such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis, gene transfection, real-time reverse transcription-PCR, Western blotting, invasion, and electrophoretic mobility shift assay for measuring DNA-binding activity of nuclear factor-κB (NF-κB), we found that ERRP caused marked inhibition of pancreatic cancer cell growth. This was accompanied by increased apoptosis and concomitant attenuation of Notch-1 and NF-κB and down-regulation of NF-κB downstream genes, such as matrix metalloproteinase-9 and vascular endothelial growth factor, resulting in the inhibition of pancreatic cancer cell invasion through the Matrigel. We also found that down-regulation of Notch-1 by small interfering RNA before ERRP treatment resulted in enhanced cell growth inhibition and apoptosis. Our data suggest that the ERRP-mediated inactivation of EGFR, Notch-1, NF-κB, and its downstream target genes contributed to the inhibition of cell growth and invasion. We conclude that ERRP could be an effective agent for inhibiting tumor growth and invasion for the treatment of pancreatic cancer. (Cancer Res 2006; 66(15): 7653-60)
Ekphrasis, Lorenzo Lotto's Annunciation, and the Hermeneutics of Suspicion
Authors: Padgett Jacqueline Olson 
Published: August 2006

AbstractLorenzo Lotto's Recanati Annunciation develops the second of the traditional pericopes in St. Luke's narrative of the Annunciation, presenting to the spectator the Virgin's startled reaction to the arrival of the angel Gabriel and suggesting that we might employ a hermeneutics of suspicion in reading the Gospel text. Recent literary responses to Lotto's painting and to the Lukan text engage in a similar hermeneutics to offer an understanding of personal and cultural responses to the Annunciation narrative and to present at times a counter-narrative.
Abkhaz Loans in Megrelian
Authors: Chirikba Vyacheslav 
Published: August 2006

AbstractThe paper presents a thorough investigation of the Abkhaz borrowings in Megrelian, including structural loans, grammatical elements, adjectives, adverbs, numerals, and appellativa (anatomical and medical terms, household items, terms related to husbandry and pasture, floristic and zoological names, religious terms, landscape, food, etc.). The author examines also the cases of the Abkhaz influence on Megrelian onomasticon.
Estimating Soil Wetness from the GOES Sounder
Authors: Rabin Robert M. , Schmit Timothy J. 
Published: August 2006

Abstract
In this note, the relationship between the observed daytime rise in surface radiative temperature, derived from the Geostationary Operational Environmental Satellites (GOES) sounder clear-sky data, and modeled soil moisture is explored over the continental United States. The motivation is to provide an infrared (IR) satellite–based index for soil moisture, which has a higher resolution than possible with the microwave satellite data. The daytime temperature rise is negatively correlated with soil moisture in most areas. Anomalies in soil moisture and daytime temperature rise are also negatively correlated on monthly time scales. However, a number of exceptions to this correlation exist, particularly in the western states. In addition to soil moisture, the capacity of vegetation to generate evapotranspiration influences the amount of daytime temperature rise as sensed by the satellite. In general, regions of fair to poor vegetation health correspond to the relatively high temperature rise from the satellite. Regions of favorable vegetation match locations of lower-than-average temperature rise.
A Quality Control Concept for Radar Reflectivity, Polarimetric Parameters, and Doppler Velocity
Authors: Friedrich Katja , Hagen Martin , Einfalt Thomas 
Published: August 2006

AbstractOver the last few years the use of weather radar data has become a fundamental part of various applications like rain-rate estimation, nowcasting of severe weather events, and assimilation into numerical weather prediction models. The increasing demand for radar data necessitates an automated, flexible, and modular quality control. In this paper a quality control procedure is developed for radar reflectivity factors, polarimetric parameters, and Doppler velocity. It consists of several modules that can be extended, modified, and omitted depending on the user requirement, weather situation, and radar characteristics. Data quality is quantified on a pixel-by-pixel basis and encoded into a quality-index field that can be easily interpreted by a nontrained end user or an automated scheme that generates radar products. The quality-index algorithms detect and quantify the influence of beam broadening, the height of the first radar echo, ground clutter contamination, return from non-weather-related objects, and attenuation of electromagnetic energy by hydrometeors on the quality of the radar measurement. The quality-index field is transferred together with the radar data to the end user who chooses the amount of data and the level of quality used for further processing. The calculation of quality-index fields is based on data measured by the polarimetric C-band Doppler radar (POLDIRAD) located in the Alpine foreland in southern Germany.
Nef interference with HIV-1–specific CTL antiviral activity is epitope specific
Authors: Adnan Sama , Balamurugan Arumugam , Trocha Alicja , Bennett Michael S. , Ng Hwee L. , Ali Ayub , Brander Christian , Yang Otto O. 
Published: August 2006

AbstractHIV-1 Nef and HIV-1–specific cytotoxic T lymphocytes (CTLs) have important and opposing roles in the immunopathogenesis of HIV-1 infection. Nef-mediated down-modulation of HLA class I on infected cells can confer resistance to CTL clearance, but the factors determining the efficiency of this process are unknown. This study examines the impact of Nef on the antiviral activity of several CTL clones recognizing epitopes from early and late HIV-1 proteins, restricted by HLA-A, -B, and -C molecules. CTL-targeting epitopes in early proteins remained susceptible to the effects of Nef, although possibly to a lesser degree than CTL-targeting late protein epitopes, indicating that significant Nef-mediated HLA down-regulation can precede even the presentation of early protein-derived epitopes. However, HLA-C–restricted CTLs were unaffected by Nef, consistent with down-regulation of cell-surface HLA-A and -B but not HLA-C molecules. Thus, CTLs vary dramatically in their susceptibility to Nef interference, suggesting differences in the relative importance of HLA-A– and HLA-B– versus HLA-C–restricted CTLs in vivo. The data thus indicate that HLA-C–restricted CTLs may have an under-appreciated antiviral role in the setting of Nef in vivo and suggest a benefit of promoting HLA-C–restricted CTLs for immunotherapy or vaccine development.
Optimization of immunomagnetic separation for cord blood-derived hematopoietic stem cells
Authors: Kekarainen Tuija , Mannelin Sirkka , Laine Jarmo , Jaatinen Taina 
Published: August 2006

Abstract

Background
There is a growing interest in cord blood as a source of primitive stem cells with the capacity for multilineage differentiation. Pure cell fractions are needed for the characterization and in vitro expansion of stem cells as well as for their use in preclinical research. However, enrichment of stem cells is challenging due to the lack of stem cell-specific markers and gentle protocols for the isolation of highly pure stem cell fractions. Protocols developed for the enrichment of peripheral blood-derived stem cells have been found to be suboptimal for cord blood.

Results
In this study, immunomagnetic cell sorting protocols to purify CD34+, CD133+ and Lin- cells from fresh and cryopreserved cord blood were optimized. Reproducible purities of up to 97% were reached. The selected cells were highly viable having substantial colony-forming potential.

Conclusion
The optimized protocols enable rapid enrichment of highly pure hematopoietic stem cells from both fresh and cryopreserved cord blood.
Inspiratory resistances facilitate the diaphragm response to transcranial stimulation in humans
Authors: Locher Chrystèle , Raux Mathieu , Fiamma Marie-Noelle , Morélot-Panzini Capucine , Zelter Marc , Derenne Jean-Philippe , Similowski Thomas , Straus Christian 
Published: August 2006

Abstract

Background
Breathing in humans is dually controlled for metabolic (brainstem commands) and behavioral purposes (suprapontine commands) with reciprocal modulation through spinal integration. Whereas the ventilatory response to chemical stimuli arises from the brainstem, the compensation of mechanical loads in awake humans is thought to involve suprapontine mechanisms. The aim of this study was to test this hypothesis by examining the effects of inspiratory resistive loading on the response of the diaphragm to transcranial magnetic stimulation.

Results
Six healthy volunteers breathed room air without load (R0) and then against inspiratory resistances (5 and 20 cmH2O/L/s, R5 and R20). Ventilatory variables were recorded. Transcranial magnetic stimulation (TMS) was performed during early inspiration (I) or late expiration (E), giving rise to motor evoked potentials (MEPs) in the diaphragm (Di) and abductor pollicis brevis (APB). Breathing frequency significantly decreased during R20 without any other change. Resistive breathing had no effect on the amplitude of Di MEPs, but shortened their latency (R20: -0.903 ms, p = 0.03) when TMS was superimposed on inspiration. There was no change in APB MEPs.

Conclusion
Inspiratory resistive breathing facilitates the diaphragm response to TMS while it does not increase the automatic drive to breathe. We interpret these findings as a neurophysiological substratum of the suprapontine nature of inspiratory load compensation in awake humans.
Factors affecting left ventricular remodeling after valve replacement for aortic stenosis. An overview
Authors: Villa Emmanuel , Troise Giovanni , Cirillo Marco , Brunelli Federico , Tomba Margherita Dalla , Mhagna Zen , Tasca Giordano , Quaini Eugenio 
Published: August 2006

Abstract
Although a small percentage of patients with critical aortic stenosis do not develop left ventricle hypertrophy, increased ventricular mass is widely observed in conditions of increased afterload. There is growing epidemiological evidence that hypertrophy is associated with excess cardiac mortality and morbidity not only in patients with arterial hypertension, but also in those undergoing aortic valve replacement. Valve replacement surgery relieves the aortic obstruction and prolongs the life of many patients, but favorable or adverse left ventricular remodeling is affected by a large number of factors whose specific roles are still a subject of debate. Age, gender, hemodynamic factors, prosthetic valve types, myocyte alterations, interstitial structures, blood pressure control and ethnicity can all influence the process of left ventricle mass regression, and myocardial metabolism and coronary artery circulation are also involved in the changes occurring after aortic valve replacement. The aim of this overview is to analyze these factors in the light of our experience, elucidate the important question of prosthesis-patient mismatch by considering the method of effective orifice area, and discuss surgical timings and techniques that can improve the management of patients with aortic valve stenosis and maximize the probability of mass regression.
Predictors of self-rated health: a 12-month prospective study of IT and media workers
Authors: Hasson Dan , Arnetz Bengt B , Theorell Töres , Anderberg Ulla Maria 
Published: August 2006

Abstract

Objective
The aim of the present study was to determine health-related risk and salutogenic factors and to use these to construct prediction models for future self-rated health (SRH), i.e. find possible characteristics predicting individuals improving or worsening in SRH over time (0–12 months).

Methods
A prospective study was conducted with measurements (physiological markers and self-ratings) at 0, 6 and 12 months, involving 303 employees (187 men and 116 women, age 23–64) from four information technology and two media companies.

Results
There were a multitude of statistically significant cross-sectional correlations (Spearman's Rho) between SRH and other self-ratings as well as physiological markers. Predictors of future SRH were baseline ratings of SRH, self-esteem and social support (logistic regression), and SRH, sleep quality and sense of coherence (linear regression).

Conclusion
The results of the present study indicate that baseline SRH and other self-ratings are predictive of future SRH. It is cautiously implied that SRH, self-esteem, social support, sleep quality and sense of coherence might be predictors of future SRH and therefore possibly also of various future health outcomes.