bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Expression of Insulin-like Growth Factor-II Messenger RNA–Binding Protein 1 Is Associated with Tumor Progression in Patients with Lung Cancer
Authors: Kato Tatsuya , Hayama Satoshi , Yamabuki Takumi , Ishikawa Nobuhisa , Miyamoto Masaki , Ito Tomoo , Tsuchiya Eiju , Kondo Satoshi , Nakamura Yusuke , Daigo Yataro 
Published: January 2007

Abstract
Purpose: To identify novel biomarkers and therapeutic targets for lung cancers, we screened for genes that were highly transactivated in a large proportion of non–small cell lung cancers (NSCLC) using a cDNA microarray representing 27,648 genes.
Experimental Design: A gene encoding insulin-like growth factor-II mRNA-binding protein 1 (IMP-1) was selected as a candidate (≥3-fold expression than in normal lung tissue in about 70% of NSCLCs). Tumor tissue microarray was applied to examine expression of IMP-1 protein in archival lung cancer samples from 267 patients and investigated its clinicopathologic significance. A role of IMP-1 in cancer cell growth and/or survival was examined by small interfering RNA experiments. Cellular invasive activity of IMP-1 on mammalian cells was examined using Matrigel assays. mRNAs associated with IMP-1 in cancer cells were also isolated by RNA immunoprecipitation followed by cDNA microarray analysis.
Results: Positive immunostaining of IMP-1 was correlated with male (P = 0.0001), tumor size (P = 0.0003), non-adenocarcinoma histology (P &lt; 0.0001), smoking history (P = 0.0005), non–well-differentiated tumor grade (P = 0.0001), and poor prognosis (P = 0.0053). Suppression of IMP-1 expression with small interfering RNA effectively suppressed growth of NSCLC cells. In addition, we identified that exogenous expression of IMP-1 increased the migratory activity of mammalian cells. IMP-1 was able to bind to mRNAs encoding a variety of proteins involved in signal transduction, cell cycle progression, cell adhesion and cytoskeleton, and various types of enzymatic activities.
Conclusions: These results suggest that IMP-1 expression is likely to play important roles in lung cancer development and progression, and that IMP-1 is a prognostic biomarker and a promising therapeutic target for lung cancer.
Antigenic Profiling of Glioma Cells to Generate Allogeneic Vaccines or Dendritic Cell–Based Therapeutics
Authors: Zhang Jian Gang , Eguchi Junichi , Kruse Carol A. , Gomez German G. , Fakhrai Habib , Schroter Stephanie , Ma Wenxue , Hoa Neil , Minev Boris , Delgado Christina , Wepsic H. Terry , Okada Hideho , Jadus Martin R. 
Published: January 2007

AbstractPurpose: Allogeneic glioma cell lines that are partially matched to the patient at class I human leukocyte antigen (HLA) loci and that display tumor-associated antigens (TAA) or antigenic precursors [tumor antigen precursor proteins (TAPP)] could be used for generating whole tumor cell vaccines or, alternatively, for extraction of TAA peptides to make autologous dendritic cell vaccines.Experimental Design: Twenty human glioma cell lines were characterized by molecular phenotyping and by flow cytometry for HLA class I antigen expression. Twelve of the 20 cell lines, as well as analyses of freshly resected glioma tissues, were further characterized for protein and/or mRNA expression of 16 tumor antigen precursor proteins or TAA.Results: These 20 human glioma cell lines potentially cover 77%, 85%, and 78% of the U.S. Caucasian population at HLA-A, HLA-B, and HLA-C alleles, respectively. All cells exhibited multiple TAA expressions. Most glioma cells expressed antigen isolated from immunoselected melanoma-2 (Aim-2), B-cyclin, EphA2, GP100, β1,6-N-acetylglucosaminyltransferase V (GnT-V), IL13Rα2, Her2/neu, hTert, Mage, Mart-1, Sart-1, and survivin. Real-time PCR technology showed that glioblastoma specimens expressed most of the TAA as well. Tumor-infiltrating lymphocytes and CD8+ CTL killed T2 cells when loaded with specific HLA-A2+ restricted TAA, or gliomas that were both HLA-A2+ and also positive for specific TAA (Mart-1, GP100, Her2/neu, and tyrosinase) but not those cells negative for HLA-A2 and/or lacking the specific epitope.Conclusions: These data provide proof-in-principle for the use of allogeneic, partially HLA patient–matched glioma cells for vaccine generation or for peptide pulsing with allogeneic glioma cell extracts of autologous patient dendritic cells to induce endogenous CTL in brain tumor patients.
Genetic Deletions in Sputum as Diagnostic Markers for Early Detection of Stage I Non–Small Cell Lung Cancer
Authors: Li Ruiyun , Todd Nevins W. , Qiu Qi , Fan Tao , Zhao Richard Y. , Rodgers William H. , Fang Hong-Bin , Katz Ruth L. , Stass Sanford A. , Jiang Feng 
Published: January 2007

Abstract
Purpose: Analysis of molecular genetic markers in biological fluids has been proposed as a powerful tool for cancer diagnosis. We have characterized in detail the genetic signatures in primary non–small cell lung cancer, which provided potential diagnostic biomarkers for lung cancer. The aim of this study was to determine whether the genetic changes can be used as markers in sputum specimen for the early detection of lung cancer.
Experimental Design: Genetic aberrations in the genes HYAL2, FHIT, and SFTPC were evaluated in paired tumors and sputum samples from 38 patients with stage I non–small cell lung cancer and in sputum samples from 36 cancer-free smokers and 28 healthy nonsmokers by using fluorescence in situ hybridization.
Results: HYAL2 and FHIT were deleted in 84% and 79% tumors and in 45% and 40% paired sputum, respectively. SFTPC was deleted exclusively in tumor tissues (71%). There was concordance of HYAL2 or FHIT deletions in matched sputum and tumor tissues from lung cancer patients (r = 0.82, P = 0.04; r = 0.84, P = 0.03), suggesting that the genetic changes in sputum might indicate the presence of the same genetic aberrations in lung tumors. Furthermore, abnormal cells were found in 76% sputum by detecting combined HYAL2 and FHIT deletions whereas in 47% sputum by cytology, of the cancer cases, implying that detecting the combination of HYAL2 and FHIT deletions had higher sensitivity than that of sputum cytology for lung cancer diagnosis. In addition, HYAL2 and FHIT deletions in sputum were associated with smoking history of cancer patients and smokers (both P &lt; 0.05).
Conclusions: Tobacco-related HYAL2 and FHIT deletions in sputum may constitute diagnostic markers for early-stage lung cancer.
Update on the Application of Interleukin-2 in the Treatment of Renal Cell Carcinoma
Authors: McDermott David F. 
Published: January 2007

Abstract
High-dose bolus interleukin 2 (IL-2) was granted Food and Drug Administration approval based on its ability to produce durable complete responses in a small number of patients with metastatic renal cell carcinoma. Results from randomized phase 3 trials suggest that regimens involving lower doses of IL-2, either alone or in combination with IFN, produce fewer tumor regressions of less overall quality. Given the toxicity, expense, and limited efficacy of this treatment, recent studies have focused on identifying predictors of response (or resistance) to IL-2 therapy. This year, investigators launched a clinical trial designed to prospectively determine if patients who are more likely to respond to high-dose IL-2 can be identified before starting therapy. As the list of effective therapies for metastatic renal cell carcinoma grows, improvements in patient selection will be necessary to ensure that patients who might attain a durable remission with IL-2 will not miss this opportunity.
Reduced Mammographic Density with Use of a Gonadotropin-Releasing Hormone Agonist–Based Chemoprevention Regimen in BRCA1 Carriers
Authors: Weitzel Jeffrey N. , Buys Saundra S. , Sherman William H. , Daniels Anna Marie , Ursin Giske , Daniels John R. , MacDonald Deborah J. , Blazer Kathleen R. , Pike Malcolm C. , Spicer Darcy V. 
Published: January 2007

Abstract
Purpose: Women with a BRCA1 mutation (BRCA1mut) need risk reduction options beyond mastectomy and oophorectomy. We evaluated the efficacy, safety, and tolerability of hormonal chemoprevention with a gonadotropin-releasing hormone agonist (GnRHA) with low-dose add-back steroids in BRCA1mut carriers.
Experimental Design: The 12-month open label clinical trial used the GnRHA deslorelin, ultra-low-dose estradiol (E2), and replacement testosterone, administered via daily intranasal spray in premenopausal women with a BRCA1mut, and intermittent oral medroxyprogesterone acetate. The end points included mammographic percent density, bone mineral density, endometrial hyperplasia, symptom inventory, and quality of life (Medical Outcomes SF-36 survey).
Results: Six of eight BRCA1mut women (mean age, 30.3 years; range, 25-36 years) completed the study. Mammographic percent density was significantly reduced at 12 months (median absolute mammographic percent density decrease, 8.3%; P = 0.043), representing a 29.2% median reduction in mammographic percent density. Bone mineral density remained within reference limits for all participants; there were no cases of atypical endometrial hyperplasia and menses resumed within a median of 67 days (range, 35-110 days) after last drug treatment day. The treatment was well tolerated; hypoestrogenic side effects were minimal and transient; and there were no significant changes in quality of life.
Conclusions: The GnRHA deslorelin, with low-dose add-back steroids, was well tolerated and significantly decreased mammographic percent density in BRCA1mut carriers. This regimen may reduce breast cancer risk and improve the usefulness of mammographic surveillance by reducing density. This is the first demonstration, to our knowledge, of a direct reduction of mammographic densities in young BRCA1mut carriers.
Opportunities and Obstacles to Combination Targeted Therapy in Renal Cell Cancer
Authors: Sosman Jeffrey A. , Puzanov Igor , Atkins Michael B. 
Published: January 2007

Abstract
The treatment of advanced renal cell carcinoma (RCC) has undergone a major change with the development of potent angiogenesis inhibitors and targeted agents. Several multitargeted tyrosine kinase inhibitors, sorafenib and sunitinib, have already been approved for the treatment of advanced RCC. Temsirolimus (CCI-779), a mammalian target of rapamycin inhibitor, has shown a survival advantage over IFN in advanced, poor-prognosis RCC patients. Bevacizumab, an antibody targeting vascular endothelial growth factor (VEGF) A, has also shown promising clinical activity. Benefits attributable to these agents have been recognized by high objective response rates (sunitinib), significant increases in progression-free survival (sunitinib, sorafenib and bevacizumab), or improved overall survival (temsirolimus). These agents mediate much of their effect through inhibition of the hypoxia-inducible factor (HIF)-VEGF-VEGF receptor axis. Their inhibitory activity for the signaling of platelet-derived growth factor (PDGF) receptor β or kinases like c-Raf may contribute to the antitumor effects of the multitargeted kinase inhibitors. Nevertheless, all four single agents rarely, if ever, induce complete responses and, at present, all patients develop resistance and, ultimately, progress during therapy. A critical need exists to develop strategies that may increase the degree of the antitumor effects with the hope of inducing more complete responses impeding the onset of or elimination of refractory disease. Combinations of these and other targeted agents may overcome the resistance that develops with single-agent therapy and could be incorporated either as part of initial therapy or later when disease resistance develops. Approaches aimed at combining these agents can be based on the genetics and biology of clear cell RCC. von Hippel-Lindau loss leads to an increase in cellular levels of HIF (HIF-1α or HIF-2α) leading to increased expression of a number of hypoxia-regulated genes critical to cancer progression. Combinations of targeted agents may block several of these mediators (VEGF, epidermal growth factor receptor, and PDGF), so-called horizontal blockade. Blockade could also take place at two levels of the pathways (vertical blockade), either at HIF and VEGF or at VEGF and VEGF receptor signaling. Many of the above strategies are ongoing and will require careful phase 1 determination of toxicity and even more rigorous phase 2 analysis before moving onto phase 3 trials.
Intercomparison of Water Vapor Data Measured with Lidar during IHOP_2002. Part II: Airborne-to-Airborne Systems
Authors: Behrendt Andreas , Wulfmeyer Volker , Schaberl Thorsten , Bauer Hans-Stefan , Kiemle Christoph , Ehret Gerhard , Flamant Cyrille , Kooi Susan , Ismail Syed , Ferrare Richard , Browell Edward V. , Whiteman David N. 
Published: January 2007

AbstractThe dataset of the International H2O Project (IHOP_2002) gives the first opportunity for direct intercomparisons of airborne water vapor lidar systems and allows very important conclusions to be drawn for future field campaigns. Three airborne differential absorption lidar (DIAL) systems were operated simultaneously during some IHOP_2002 missions: the DIAL of Deutsches Zentrum für Luft- und Raumfahrt (DLR), the Lidar Atmospheric Sensing Experiment (LASE) of the National Aeronautics and Space Administration (NASA) Langley Research Center, and the Lidar Embarque pour l’etude des Aerosols et des Nuages de l’interaction Dynamique Rayonnement et du cycle de l’Eau (LEANDRE II) of the Centre National de la Recherche Scientifique (CNRS). Data of one formation flight with DLR DIAL and LEANDRE II were investigated, which consists of 54 independent profiles of the two instruments measured with 10-s temporal average. For the height range of 1.14–1.64 km above sea level, a bias of (−0.41 ± 0.16) g kg−1 or −7.9% ± 3.1% was found for DLR DIAL compared to LEANDRE II (LEANDRE II drier) as well as root-mean-square (RMS) deviations of (0.87 ± 0.18) g kg−1 or 16.9% ± 3.5%. With these results, relative bias values of −9.3%, −1.5%, +2.7%, and +8.1% result for LEANDRE II, DLR DIAL, the scanning Raman lidar (SRL), and LASE, respectively, using the mutual bias values determined in Part I for the latter three sensors. From the three possible profile-to-profile intercomparisons between DLR DIAL and LASE, one case cannot provide information on the system performances due to very large inhomogeneity of the atmospheric water vapor field, while one of the two remaining two cases showed a difference of −4.6% in the height range of 1.4–3.0 km and the other of −25% in 1.3–3.8 km (in both cases DLR DIAL was drier than LASE). The airborne-to-airborne comparisons showed that if airborne water vapor lidars are to be validated down to an accuracy of better than 5% in the lower troposphere, the atmospheric variability of water vapor has to be taken into account down to scales of less than a kilometer unless a sufficiently large number of intercomparison cases is available to derive statistically solid biases and RMS deviations. In conclusion, the overall biases between the water vapor data of all three airborne lidar systems operated during IHOP_2002 are smaller than 10% in the present stage of data evaluation, which confirms the previous estimates of the instrumental accuracies for all the systems.
Application of a Differential Fuel-Cell Analyzer for Measuring Atmospheric Oxygen Variations
Authors: Stephens Britton B. , Bakwin Peter S. , Tans Pieter P. , Teclaw Ron M. , Baumann Daniel D. 
Published: January 2007

Abstract
A commercially available differential fuel-cell analyzer has been adapted to make field-based ppm-level measurements of atmospheric O2 variations. With the implementation of rapid calibrations and active pressure and flow control, the analysis system described here has a 1σ precision of ±2.5 per meg (≈0.5 ppm) for a 2-min measurement. Allowing for system stabilization after switching inlet lines, a 6-min measurement with a precision of ±1.4 per meg (≈0.3 ppm) every 20 min is obtained. The elimination of biases in any atmospheric O2 measurement depends critically on careful gas-handling procedures, and after screening for known sources of bias a comparability of ±10 per meg (≈2 ppm) with the present setup is estimated. In comparison to existing techniques, the relatively small size, low cost, fast response, motion insensitivity, and ease of implementation of the fuel-cell analyzer make it particularly useful for a wide range of unattended field applications. This system has been used to measure atmospheric O2 concentrations at the WLEF tall-tower research site in northern Wisconsin semicontinuously from June 2000 to December 2003. These measurements represent the first extended O2 record in and above a forest ecosystem, and are being used to investigate global carbon budgeting, plant physiology, continental boundary layer mixing and synoptic transport, and potential means of industrial emission verification. In this paper, the measurement technique is described in detail and several weeks of data are presented to illustrate its performance.
Drop-in services: Findings from an evaluation of the Healthy Living Centre programme in Scotland
Authors: Truman J , Rankin D , Backett-Milburn K , Platt S 
Published: January 2007

Objective To explore the diverse roles of drop-in services in the HLC sector; to develop further the classification of drop-in services offered by earlier studies; and to provide an example of some the challenges faced by HLCs in their attempts to tackle poor health using area-based methods with vulnerable, hard-to-reach users. Setting Scottish Healthy Living Centres. Methods Six Healthy Living Centres were purposively selected to reflect some of the diversity within the Healthy Living Centre programme in Scotland. Semi-structured interviews were undertaken with 10–15 respondents in each of the case studies. Results The term ‘drop-in’ was used to describe services which varied in respect of activities, aims, management and resources. This variation reflected the specific context and understanding of health in individual HLCs. Some addressed health lifestyles, reflecting an individualistic model of health based on risk factor assessment; others focused more broadly on the fundamental determinants of ill health, such as employment, education, poverty and social well being,reflecting a social model of health. Conclusions Our findings support and expand earlier work in the area.We have produced a revised typology of drop-in services, identifying ‘user-defined’ in addition to the previously developed categories of ‘consumer run’ and ‘consumer involved’ services.
Predicting default from smoking cessation treatment following enrolment
Authors: Challenger Alison , Coleman Tim , Lewis Sarah 
Published: January 2007

Objective To determine which factors predict default from subsequent treatment sessions after initial enrolment and attendance at a large, English smoking cessation service. Design Cross-sectional survey using data obtained at smokers' initial enrolment attendance to compare the characteristics of those who subsequently default with those who do not. Participants and setting 2516 smokers who attended at least one appointment with a smoking cessation service serving the Nottingham City area, UK, in a two year period starting from 1 October 2001. Results The 2516 smokers who consented for their data to be used in this analysis comprised 78.8 per cent of all smokers enrolled into the smoking cessation service during the study period. Of these, 73.9 per cent (1892) attended subsequent appointments, whilst 21.6 per cent defaulted (i.e. failed to re-attend for treatment after the initial appointment). Default from treatment was independently associated with younger age, heavier smoking, living alone or in a house with a smoker, and being less motivated to stop smoking, but was unrelated to smokers' routes of referral to the service. Conclusions Further work is required to explain why described factors are associated with default from smoking cessation treatment in this service and to determine whether similar factors influence this in other services. Our results suggest that, to minimize default, smoking cessation services should, at initial enrolment consultations, employ strategies to increase smokers' motivation to stop, combat nicotine addiction and the influence of other smokers at home.
Comparison of polymethoxyethylacrylate-coated circuits with leukocyte filtration and reduced heparinization protocol on heparin-bonded circuits in different risk cohorts
Authors: Gunaydin Serdar , McCusker Kevin , Vijay Venkataramana , Isbir Selim , Sari Tamer , Onur Mehmet Ali , Gurpinar Aylin , Sezgin Aysun , Sargon Mustafa F , Tezcaner Tevfik , Zorlutuna Yaman 
Published: January 2007

Objectives: The relative benefits of strategic leukofiltration on polymer-coated and low-dose heparin protocol on heparin-coated circuits were studied across EuroSCORE patient risk strata for three different cohorts. Methods: In a prospective, randomized study, 270 patients undergoing coronary artery bypass grafting were allocated into three groups (n = 90): Group 1 -polymethoxyethylacrylate-coated circuits+leukocyte filters; Group 2 -polypeptide-based heparin-bonded circuits with reduced heparinization; and Group 3 -Control: uncoated circuits. Each group was further divided into three subgroups (n = 30), with respect to low- (EuroSCORE 0-2), medium- (3-5), and high- (6+) risk patients. Blood samples were collected at T1: following induction of anesthesia; T2: following heparin administration; T3: 15 min after CPB; T4: before cessation of CPB; T5: 15 min after protamine reversal; and T6: ICU. Results: In high-risk cohorts, leukocyte counts demonstrated significant differences at T4 and T5 in Group 1, and at T4 in Group 2. Platelet counts were preserved significantly better at T4 and T5 in both groups (p <0.05 versus control). Serum IL-2 and C3a levels were significantly lower at T3, T4 and T5 in Group 1, and T4 and T5 in Group 2 (p <0.05). Postoperative bleeding, respiratory support time and incidence of atrial fibrillation were lower in the study groups versus control. Cell counts on filter mesh and heparin-coated fibers/circuits were significantly higher in the high-risk cohorts versus uncoated fibers. Phagocytic capacity increased on filter mesh, especially in high-risk specimens. SEM evaluation demonstrated better preserved coated circuits. Conclusion: Leukofiltration and coating reduced platelet adhesion, protein adsorption, atrial fibrillation and reduced heparinization acted via modulation of systemic inflammatory response in high-risk groups.
Venous line filtration: a novel technique for cases involving inferior vena caval and right atrial tumor and associated thrombus: a two-case series
Authors: Smigla Gregory R , Lawson D Scott , Kaemmer David D , Shearer Ian R 
Published: January 2007

Two patients are presented with right atrial tumors, who were considered to be at risk for tumor thrombus migration down the venous line into the cardiopulmonary bypass (CPB) circuit during surgical excision, which may lead to compromised or interrupted venous drainage. An arterial line filter was placed in the venous line to capture any material that might become dislodged and embolize into the circuit. Vacuum-assisted venous drainage, at approximately -50 mmHg, was used to overcome any resistance caused by the filter in the venous line. In one case, tumor thrombus obstructed the filter, requiring the use of the bypass line around the filter, so venous return could be maintained. In both cases, thrombus was found in the filter. The first case was a 44-year-old female (81 kg, 137 cm, body surface area (BSA) 1.66 m2) who presented with a metastatic pheochromocytoma with associated thrombus arising from the left adrenal gland and extending into the inferior vena cava (IVC) and right atrium. The second case was a 37-year-old male (95 kg, 178 cm, BSA 2.17 m2), who presented with a very large angiosarcoma tumor involving almost the entire right atrium. We have shown that venous line filtration with vacuum-assisted venous drainage can be performed safely, and should be considered in cases where there is tumor thrombus in the vena cava or right atrium, which may threaten venous return.