bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Detection of Chemoradioresponse in Esophageal Carcinoma by 3′-Deoxy-3′-3H-Fluorothymidine Using Preclinical Tumor Models
Authors: Apisarnthanarax Smith , Alauddin Mian M. , Mourtada Firas , Ariga Hisanori , Raju Uma , Mawlawi Osama , Han Dongmei , Bornmann William G. , Ajani Jaffer A. , Milas Luka , Gelovani Juri G. , Chao K.S. Clifford 
Published: August 2006

Abstract
Purpose: Early identification of esophageal cancer patients who are responding or resistant to combined chemoradiotherapy may lead to individualized therapeutic approaches and improved clinical outcomes. We assessed the ability of 3′-deoxy-3′-18F-fluorothymidine positron emission tomography (FLT-PET) to detect early changes in tumor proliferation after chemoradiotherapy in experimental models of esophageal carcinoma.
Experimental Design: The in vitro and ex vivo tumor uptake of [3H]FLT in SEG-1 human esophageal adenocarcinoma cells were studied at various early time points after docetaxel plus irradiation and validated with conventional assessments of cellular proliferation [thymidine (Thd) and Ki-67] and [18F]FLT micro-PET imaging. Imaging-histologic correlation was determined by comparing spatial Ki-67 and [18F]FLT distribution in autoradiographs. Comparison with fluorodeoxyglucose (FDG) was done in all experiments.
Results: In vitro [3H]FLT and [3H]Thd uptake rapidly decreased in SEG-1 cells 24 hours after docetaxel with a maximal reduction of over 5-fold (P = 0.005). The [3H]FLT tumor-to-muscle uptake ratio in xenografts declined by 75% compared with baseline (P &lt; 0.005) by 2 days after chemoradiotherapy, despite the lack of change in tumor size. In contrast, the decline of [3H]FDG uptake was gradual and less pronounced. Tumor uptake of [3H]FLT was more closely correlated with Ki-67 expression (r = 0.89, P &lt; 0.001) than was [3H]FDG (r = 0.39, P = 0.08). Micro-PET images depicted similar trends in reduction of [18F]FLT and [18F]FDG tumor uptake. Autoradiographs displayed spatial correlations between [18F]FLT uptake and histologic Ki-67 distribution in preliminary studies.
Conclusions: FLT-PET is suitable and more specific than FDG-PET for depicting early reductions in tumor proliferation that precede tumor size changes after chemoradiotherapy.
Intratumoral Therapy with IL13-PE38 Results in Effective CTL-Mediated Suppression of IL-13Rα2-Expressing Contralateral Tumors
Authors: Kawakami Koji , Terabe Masaki , Kioi Mitomu , Berzofsky Jay A. , Puri Raj K. 
Published: August 2006

AbstractPurpose: IL13-PE38, a targeted cytotoxin comprised of interleukin 13 (IL-13) and a mutated form of Pseudomonas exotoxin, induces specific killing of tumor cells expressing abundant levels of the IL-13Rα2 chain. We hypothesized that tumor cells killed by the cytotoxin may release antigens and/or apoptotic bodies when cells are dying, which then induce adoptive immunity, and that the PE38 portion of IL13-PE38 may act as a stimulant for the induction of a CTL response.Experimental Design: To test this hypothesis, we established D5 melanoma tumors with or without expression of the IL-13Rα2 chain in both flanks of C57BL/6 mice, and then IL13-PE38 was injected in the right flank tumors only.Results and Conclusions: When animals with IL-13Rα2-expressing D5 tumor (right) were injected with IL13-PE38, right flank tumors expressing the IL-13Rα2 chain not only showed dramatic regression but contralateral tumors (left flank) also showed tumor regression. Cell depletion experiments in tumor-bearing animals indicated that both CD8+ and CD4+ T cells contribute to the regression of contralateral tumors through CTL activation in the periphery and cellular infiltration into tumors. In addition, intratumoral treatment into s.c. tumors of mice bearing metastatic lung tumors with IL13-PE38 showed not only the reduction of treated s.c. tumor but also the reduction of lung metastasis. Thus, IL13-PE38 mediates an antitumor effect not only directly but also indirectly by inducing a host CD8+ T cell immune response. Accordingly, targeted cytotoxins may be used to treat local disease even if they cannot be administered systemically, and yet may still induce a reasonable systemic antitumor response.
Effect of Altering Dietary ω-6/ω-3 Fatty Acid Ratios on Prostate Cancer Membrane Composition, Cyclooxygenase-2, and Prostaglandin E2
Authors: Kobayashi Naoko , Barnard R. James , Henning Susanne M. , Elashoff David , Reddy Srinivasa T. , Cohen Pinchas , Leung Pak , Hong-Gonzalez Jenny , Freedland Stephen J. , Said Jonathan , Gui Dorina , Seeram Navindra P. , Popoviciu Laura M. , Bagga Dilprit , Heber David , Glaspy John A. , Aronson William J. 
Published: August 2006

Abstract
Purpose: To determine whether altering the dietary content of ω-6 (n-6) and ω-3 (n-3) polyunsaturated fatty acids affects the growth of androgen-sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and tumor cyclooxygenase-2 and prostaglandin E2 (PGE2) levels.
Experimental Design: Individually caged male severe combined immunodeficiency mice were fed isocaloric 20% kcal fat diets with the fat derived either primarily from n-6 fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4 (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric intake was measured 3 days per week, and tumors and serum were harvested at 8 weeks postinjection.
Results: Tumor growth rates, final tumor volumes, and serum prostate-specific antigen levels were reduced in the n-3 group relative to the n-6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and increased apoptosis (terminal nucleotidyl transferase–mediated nick end labeling staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3 group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83% reduction in PGE2 levels, and decreased vascular endothelial growth factor expression.
Conclusion: These results provide a sound basis for clinical trials evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE2 and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer.
Expression of Annexin A1 in Esophageal and Esophagogastric Junction Adenocarcinomas: Association with Poor Outcome
Authors: Wang Kim L. , Wu Tsung-Teh , Resetkova Erika , Wang Huamin , Correa Arlene M. , Hofstetter Wayne L. , Swisher Stephen G. , Ajani Jaffer A. , Rashid Asif , Hamilton Stanley R. , Albarracin Constance T. 
Published: August 2006

Abstract
Purpose: Annexin A1 (ANXA1) is a calcium-binding protein involved in arachidonic acid metabolism and epidermal growth factor receptor tyrosine kinase pathway. ANXA1 has been implicated in early squamous cell carcinogenesis of esophagus and correlates with degree of tumor differentiation. However, the role of ANXA1 in esophageal adenocarcinoma is unclear. Our goal was to evaluate ANXA1 expression and determine its prognostic significance in adenocarcinoma of the esophagus and esophagogastric junction.
Experimental Design: This study included 104 consecutive patients with primary resected esophageal and esophagogastric junction adenocarcinomas (11 stage I, 24 stage II, 53 stage III, and 16 stage IV). ANXA1 protein expression in each tumor was assessed by immunohistochemical staining of tissue microarrays. ANAX1 expression level was classified as high (≥25% of tumor cells with cytoplasmic staining), low (&lt;25% of tumor cells with cytoplasmic staining), or negative; and was correlated with clinicopathologic features and patients' outcomes.
Results: High ANXA1 expression was present in 39% (41 of 104) of tumors and was associated with higher pathologic T stage (P = 0.03) and distant metastasis (P = 0.04). High ANXA1 expression correlated with increased recurrence rate (P = 0.004) and decreased overall survival (P = 0.003) in univariate analysis. In multivariate analysis, ANXA1 expression and pN stage significantly correlated with recurrence rate (P = 0.008 and P &lt; 0.001, respectively) and overall survival (P = 0.02 and P &lt; 0.001, respectively) independent of T stage.
Conclusion: Our results indicate that high ANXA1 expression is frequent in esophageal and esophagogastric junction adenocarcinomas, correlates with more advanced pathologic T stage and the presence of distant metastasis, and is an independent prognostic factor for patient survival.
Nature, Development and Disaster in Postwar Kobe: An Exploration of the Environmental Thinking of Japanese Local Politicians
Authors: Tsu Timothy Yun Hui 
Published: August 2006

AbstractPostwar Kobe prides itself on being a "progressive" city. It attracted nation-wide attention in the Fifties and Sixties for bold and innovative infrastructure construction. Since the Seventies, without slowing down the pace of construction, it has acquired the reputation for being "environmentally enlightened." The city therefore appears to have achieved a balance between the imperatives of the "construction nation" and "green nation." This paper examines the thinking of two Kobe mayors and two governors of Hyōgo prefecture, wherein the city is located, to shed light on an aspect of environmental change in modern Japan that has been overlooked by scholars. By showing how the four heads of local government, by their own account, have tried to resolve the conflicting demands of development and conservation, this paper argues that local political leaders, in contrary to the conventional view of Japanese government, do contribute—sometimes even taking the lead—to the physical and cultural transformation of the territory under their charge.
Smad5 is dispensable for adult murine hematopoiesis
Authors: Singbrant Sofie , Moody Jennifer L. , Blank Ulrika , Karlsson Goran , Umans Lieve , Zwijsen An , Karlsson Stefan 
Published: August 2006

AbstractSmad5 is known to transduce intracellular signals from bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β (TGF-β) superfamily and are involved in the regulation of hematopoiesis. Recent findings suggest that BMP4 stimulates proliferation of human primitive hematopoietic progenitors in vitro, while early progenitors from mice deficient in Smad5 display increased self-renewal capacity in murine embryonic hematopoiesis. Here, we evaluate the role of Smad5 in the regulation of hematopoietic stem cell (HSC) fate decisions in adult mice by using an inducible MxCre-mediated conditional knockout model. Surprisingly, analysis of induced animals revealed unperturbed cell numbers and lineage distribution in peripheral blood (PB), bone marrow (BM), and the spleen. Furthermore, phenotypic characterization of the stem cell compartment revealed normal numbers of primitive lin–Sca-1+c-Kit+ (LSK) cells in Smad5–/– BM. When transplanted in a competitive fashion into lethally irradiated primary and secondary recipients, Smad5-deficient BM cells competed normally with wild-type (wt) cells, were able to provide long-term reconstitution for the hosts, and displayed normal lineage distribution. Taken together, Smad5-deficient HSCs from adult mice show unaltered differentiation, proliferation, and repopulating capacity. Therefore, in contrast to its role in embryonic hematopoiesis, Smad5 is dispensable for hematopoiesis in the adult mouse.
Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells
Authors: Rüster Brigitte , Göttig Stephan , Ludwig Ralf J. , Bistrian Roxana , Müller Stefanie , Seifried Erhard , Gille Jens , Henschler Reinhard 
Published: August 2006

AbstractTo explore the initial steps by which transplanted mesenchymal stem cells (MSCs) interact with the vessel wall in the course of extravasation, we studied binding of human MSCs to endothelial cells (ECs). In a parallel plate flow chamber, MSCs bound to human umbilical vein ECs (HUVECs) similar to peripheral-blood mononuclear cells (PBMCs) or CD34+ hematopoietic progenitors at shear stresses of up to 2 dynes/cm2. This involved rapid extension of podia, rolling, and subsequent firm adhesion that was increased when ECs were prestimulated with TNF-α. MSC binding was suppressed when ECs were pretreated with function-blocking anti–P-selectin antibody, and rolling of MSCs was induced on immobilized P-selectin, indicating that P-selectin was involved in this process. Preincubation of HUVECs with anti–VCAM-1 or of MSCs with anti–VLA-4 antibodies suppressed binding of MSCs to HUVECs but did not enhance inhibition by anti–P-selectin, indicating that both P-selectin and VCAM-1 are equally required for this process. Intravital microscopy demonstrated the capacity of MSCs to roll and adhere to postcapillary venules in vivo in a mouse model in a P-selectin–dependent manner. Thus, MSCs interact in a coordinated fashion with ECs under shear flow, engaging P-selectin and VCAM-1/VLA-4.
Role of chromosome stability and telomere length in the production of viable cell lines for somatic cell nuclear transfer
Authors: Mastromonaco Gabriela F , Perrault Steve D , Betts Dean H , King W Allan 
Published: August 2006

Abstract

Background
Somatic cell nuclear transfer (SCNT) provides an appealing alternative for the preservation of genetic material in non-domestic and endangered species. An important prerequisite for successful SCNT is the availability of good quality donor cells, as normal embryo development is dependent upon proper reprogramming of the donor genome so that embryonic genes can be appropriately expressed. The characteristics of donor cell lines and their ability to produce embryos by SCNT were evaluated by testing the effects of tissue sample collection (DART biopsy, PUNCH biopsy, post-mortem EAR sample) and culture initiation (explant, collagenase digestion) techniques.

Results
Differences in initial sample size based on sample collection technique had an effect on the amount of time necessary for achieving primary confluence and the number of population doublings (PDL) produced. Thus, DART and PUNCH biopsies resulted in cultures with decreased lifespans (<30 PDL) accompanied by senescence-like morphology and decreased normal chromosome content (<40% normal cells at 20 PDL) compared to the long-lived (>50 PDL) and chromosomally stable (>70% normal cells at 20 PDL) cultures produced by post-mortem EAR samples. Chromosome stability was influenced by sample collection technique and was dependent upon the culture's initial telomere length and its rate of shortening over cell passages. Following SCNT, short-lived cultures resulted in significantly lower blastocyst development (≤ 0.9%) compared to highly proliferative cultures (11.8%). Chromosome stability and sample collection technique were significant factors in determining blastocyst development outcome.

Conclusion
These data demonstrate the influence of culture establishment techniques on cell culture characteristics, including the viability, longevity and normality of cells. The identification of a quantifiable marker associated with SCNT embryo developmental potential, chromosome stability, provides a means by which cell culture conditions can be monitored and improved.
Dopamine presynaptically and heterogeneously modulates nucleus accumbens medium-spiny neuron GABA synapses in vitro
Authors: Geldwert Daron , Norris J Madison , Feldman Igor G , Schulman Joshua J , Joyce Myra P , Rayport Stephen 
Published: August 2006

AbstractBackgroundThe striatal complex is the major target of dopamine action in the CNS. There, medium-spiny GABAergic neurons, which constitute about 95% of the neurons in the area, form a mutually inhibitory synaptic network that is modulated by dopamine. When put in culture, the neurons reestablish this network. In particular, they make autaptic connections that provide access to single, identified medium-spiny to medium-spiny neuron synaptic connections.ResultsWe examined medium-spiny neuron autaptic connections in postnatal cultures from the nucleus accumbens, the ventral part of the striatal complex. These connections were subject to presynaptic dopamine modulation. D1-like receptors mediated either inhibition or facilitation, while D2-like receptors predominantly mediated inhibition. Many connections showed both D1 and D2 modulation, consistent with a significant functional colocalization of D1 and D2-like receptors at presynaptic sites. These same connections were subject to GABAA, GABAB, norepinephrine and serotonin modulation, revealing a multiplicity of modulatory autoreceptors and heteroreceptors on individual varicosities. In some instances, autaptic connections had two components that were differentially modulated by dopamine agonists, suggesting that dopamine receptors could be distributed heterogeneously on the presynaptic varicosities making up a single synaptic (i.e. autaptic) connection.ConclusionDifferential trafficking of dopamine receptors to different presynaptic varicosities could explain the many controversial studies reporting widely varying degrees of dopamine receptor colocalization in medium-spiny neurons, as well as more generally the diversity of dopamine actions in target areas. Longer-term changes in the modulatory actions of dopamine in the striatal complex could be due to plasticity in the presynaptic distribution of dopamine receptors on medium-spiny neuron varicosities.
Protocol for north of England and Scotland study of tonsillectomy and adeno-tonsillectomy in children (NESSTAC). A pragmatic randomised controlled trial comparing surgical intervention with conventional medical treatment in children with recurrent sore throats
Authors: Bond John , Wilson Janet , Eccles Martin , Vanoli Alessandra , Steen Nick , Clarke Ray , Zarod Andrew , Lock Catherine , Brittain Katie , Speed Chris , Rousseau Nikki 
Published: August 2006

AbstractBackgroundUncertainties surrounding the effectiveness and cost-effectiveness of childhood tonsillectomy for recurrent sore throat led the NHS Health Technology Assessment Programme to commission this research to evaluate the effectiveness and cost-effectiveness of tonsillectomy and adeno-tonsillectomy in comparison with standard non-surgical management in children aged under 16 with recurrent throat infections. The aim is to evaluate if tonsillectomy and adeno-tonsillectomy reduces the number of episodes of sore throats among children to a clinically significant extent.Methods/designA simple prospective pragmatic randomised controlled trial with economic analysis and prospective cohort study of non-trial participants comparing surgical intervention with conventional medical treatment. The treatment arm will receive tonsillectomy and adeno-tonsillectomy while in the control arm non-surgical conventional medical treatment only will be used. The primary outcome measure will be reported number of episodes of sore throat over two years with secondary outcomes measures of reported number of episodes of sore throat, otitis media and upper respiratory tract infection which invoke a GP consultation; reported number of symptom-free days; reported severity of sore throats and surgical and anaesthetic morbidity. The study will take place in five hospitals in the UK. The trial population will be 406 children aged 4–15 on their last birthday with recurrent sore throat referred by primary care to the 5 otolaryngology departments. The duration of the study is seven years (July 2001- July 2008).DiscussionAs with all pragmatic randomised controlled trials it is impossible to control the external environment in which the research is taking place. Since this trial began a number of factors have arisen which could affect the outcome including; a reduction in the incidence of respiratory tract infections, marked socio-economic differences in consultation rates, the results from the National Prospective Tonsillectomy Audit and the Government's waiting list initiatives.
Prevalence and Treatment of Metabolic Syndrome in Adolescents with Type 2 Diabetes
Authors: Sanders Brittany Harris , Lubsch Lisa M , West Donna S 
Published: August 2006

Background: The incidence of obesity and type 2 diabetes among adolescents has risen dramatically in recent years, and it is likely that many of these adolescents also have metabolic syndrome. Objective: To investigate the prevalence of metabolic syndrome in the patient population enrolled in a children's hospital type 2 diabetes clinic and to describe baseline pharmacologic treatment and adherence patterns. Methods: In this retrospective cohort study, the medical charts of 52 adolescents were reviewed. A data collection instrument was used to collect demographic data, laboratory values, medication lists, and documented adherence patterns from the patient's initial clinic visit. Data collected were used to identify patients with metabolic syndrome. Data were entered into a database and analyzed using SPSS 13.0. Results: Data were collected for 52 patients; of these, 40 (76.9%) had characteristics of metabolic syndrome meeting 3 or more of the 5 criteria, although only 8 (15.4%) were diagnosed with the metabolic syndrome. Among patients with characteristics of metabolic syndrome, 92.5% were taking a glucose-lowering drug, with 85% of those receiving metformin. Sixteen (40%) patients were receiving a blood pressure–lowering medication at baseline, and 4 (10%) were taking a lipid-lowering agent. Forty-three percent of these patients reported nonadherence to their prescribed drugs. Conclusions: Given these treatment patterns, pharmacologic management of metabolic syndrome in adolescents with type 2 diabetes may be suboptimal and may impact cardiovascular outcomes. It is important for clinicians to be aware of the incidence of type 2 diabetes and metabolic syndrome in adolescents so that treatment with lifestyle modifications and pharmacologic therapy may be implemented earlier.
Invariance of SCL‐90‐R dimensions of symptom distress in patients with peri partum pelvic pain (PPPP) syndrome
Authors: Arrindell W. A. , Barelds Dick P. H. , Janssen Irene C. M. , Buwalda Femke M. , van der Ende Jan 
Published: August 2006

Objectives. There are no studies available that have examined the factorial invariance of dimensions underlying the Symptom Checklist‐90‐Revised (SCL‐90‐R) across at least three distinct samples. In the following study, we wished to determine whether a dimensional model comprising eight primary factors previously identified in psychiatric out‐patients, phobics and the general population (Arrindell & Ettema, 2003) could be extended to a homogeneous sample of pain patients comprising females suffering from peri partum pelvic pain (PPPP) syndrome (N=413). The internal consistency and discriminant validity of the dimensions were also examined.Method. The SCL‐90‐R and measures of disability, pain‐related fear, pain intensity and fatigue were administered to the participants. The multiple group method was used to determine factorial invariance. Pearson correlations were determined between the SCL‐90‐R and aforementioned measures.Results. The factorial invariance of an 8‐dimensional model of primary factors underlying the SCL‐90‐R, namely, agoraphobia, anxiety, depression, somatization, cognitive‐performance deficits, interpersonal sensitivity‐mistrust, acting‐out hostility and sleep difficulties, was extended with success to the present sample of PPPP patients. In spite of substantial correlations between the internally consistent SCL‐90‐R symptom dimensions, some evidence of discriminant validity was reported in that specific subscales showed different patterns of correlations with measures of disability, pain‐related fear, pain intensity and fatigue.Conclusions. The 8‐dimensional system based on the work of Arrindell and Ettema (2003) was invariant across psychiatric patients, phobics, the general population and pain patients. The invariance of the SCL‐90‐R hostility dimensions may have implications for a re‐formulation of Watson and Clark's tripartite model of general distress, specific anxiety and specific depression.