bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/II Study of Oncolytic HSVGM-CSF in Combination with Radiotherapy and Cisplatin in Untreated Stage III/IV Squamous Cell Cancer of the Head and Neck
Authors: Harrington Kevin J. , Hingorani Mohan , Tanay Mary Anne , Hickey Jennifer , Bhide Shreerang A. , Clarke Peter M. , Renouf Louise C. , Thway Khin , Sibtain Amen , McNeish Iain A. , Newbold Kate L. , Goldsweig Howard , Coffin Robert , Nutting Christopher M. 
Published: July 2010

Abstract
Purpose: This study sought to define the recommended dose of JS1/34.5-/47-/GM-CSF, an oncolytic herpes simplex type-1 virus (HSV-1) encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF), for future studies in combination with chemoradiotherapy in patients with squamous cell cancer of the head and neck (SCCHN).
Experimental Design: Patients with stage III/IVA/IVB SCCHN received chemoradiotherapy (70 Gy/35 fractions with concomitant cisplatin 100 mg/m2 on days 1, 22, and 43) and dose-escalating (106, 106, 106, 106 pfu/mL for cohort 1; 106, 107, 107, 107 for cohort 2; 106, 108, 108, 108 for cohort 3) JS1/34.5-/47-/GM-CSF by intratumoral injection on days 1, 22, 43, and 64. Patients underwent neck dissection 6 to 10 weeks later. Primary end points were safety and recommended dose/schedule for future study. Secondary end points included antitumor activity (radiologic, pathologic). Relapse rates and survival were also monitored.
Results: Seventeen patients were treated without delays to chemoradiotherapy or dose-limiting toxicity. Fourteen patients (82.3%) showed tumor response by Response Evaluation Criteria in Solid Tumors, and pathologic complete remission was confirmed in 93% of patients at neck dissection. HSV was detected in injected and adjacent uninjected tumors at levels higher than the input dose, indicating viral replication. All patients were seropositive at the end of treatment. No patient developed locoregional recurrence, and disease-specific survival was 82.4% at a median follow-up of 29 months (range, 19-40 months).
Conclusions: JS1/34.5-/47-/GM-CSF combined with cisplatin-based chemoradiotherapy is well tolerated in patients with SCCHN. The recommended phase II dose is 106, 108, 108, 108. Locoregional control was achieved in all patients, with a 76.5% relapse-free rate so far. Further study of this approach is warranted in locally advanced SCCHN. Clin Cancer Res; 16(15); 4005–15. ©2010 AACR.
Epithelial Membrane Protein-2 Is a Novel Therapeutic Target in Ovarian Cancer
Authors: Fu Maoyong , Maresh Erin L. , Soslow Robert A. , Alavi Mohammad , Mah Vei , Zhou Qin , Iasonos Alexia , Goodglick Lee , Gordon Lynn K. , Braun Jonathan , Wadehra Madhuri 
Published: July 2010

Abstract
Purpose: The tetraspan protein epithelial membrane protein-2 (EMP2) has been shown to regulate the surface display and signaling from select integrin pairs, and it was recently identified as a prognostic biomarker in human endometrial cancer. In this study, we assessed the role of EMP2 in human ovarian cancer.
Experimental Design: We examined the expression of EMP2 within a population of women with ovarian cancer using tissue microarray assay technology. We evaluated the efficacy of EMP2-directed antibody therapy using a fully human recombinant bivalent antibody fragment (diabody) in vitro and ovarian cancer xenograft models in vivo.
Results: EMP2 was found to be highly expressed in &gt;70% of serous and endometrioid ovarian tumors compared with nonmalignant ovarian epithelium using a human ovarian cancer tissue microarray. Using anti-EMP2 diabody, we evaluated the in vitro response of nine human ovarian cancer cell lines with detectable EMP2 expression. Treatment of human ovarian cancer cell lines with anti-EMP2 diabodies induced cell death and retarded cell growth, and these response rates correlated with cellular EMP2 expression. We next assessed the effects of anti-EMP2 diabodies in mice bearing xenografts from the ovarian endometrioid carcinoma cell line OVCAR5. Anti-EMP2 diabodies significantly suppressed tumor growth and induced cell death in OVCAR5 xenografts.
Conclusions: These findings indicate that EMP2 is expressed in the majority of ovarian tumors and may be a feasible target in vivo. Clin Cancer Res; 16(15); 3954–63. ©2010 AACR.
White Tea Extract Induces Apoptosis in Non–Small Cell Lung Cancer Cells: the Role of Peroxisome Proliferator-Activated Receptor-γ and 15-Lipoxygenases
Authors: Mao Jenny T. , Nie Wen-Xian , Tsu I-Hsien , Jin Yu-Sheng , Rao Jian Yu , Lu Qing-Yi , Zhang Zuo-Feng , Go Vay Liang W. , Serio Kenneth J. 
Published: July 2010

AbstractEmerging preclinical data suggests that tea possess anticarcinogenic and antimutagenic properties. We therefore hypothesize that white tea extract (WTE) is capable of favorably modulating apoptosis, a mechanism associated with lung tumorigenesis. We examined the effects of physiologically relevant doses of WTE on the induction of apoptosis in non–small cell lung cancer cell lines A549 (adenocarcinoma) and H520 (squamous cell carcinoma) cells. We further characterized the molecular mechanisms responsible for WTE-induced apoptosis, including the induction of peroxisome proliferator-activated receptor-γ (PPAR-γ) and the 15-lipoxygenase (15-LOX) signaling pathways. We found that WTE was effective in inducing apoptosis in both A549 and H520 cells, and inhibition of PPAR-γ with GW9662 partially reversed WTE-induced apoptosis. We further show that WTE increased PPAR-γ activation and mRNA expression, concomitantly increased 15(S)-hydroxy-eicosatetraenoic acid release, and upregulated 15-LOX-1 and 15-LOX-2 mRNA expression by A549 cells. Inhibition of 15-LOX with nordihydroguaiaretic acid (NGDA), as well as caffeic acid, abrogated WTE-induced PPAR-γ activation and upregulation of PPAR-γ mRNA expression in A549 cells. WTE also induced cyclin-dependent kinase inhibitor 1A mRNA expression and activated caspase-3. Inhibition of caspase-3 abrogated WTE-induced apoptosis. Our findings indicate that WTE is capable of inducing apoptosis in non–small cell lung cancer cell lines. The induction of apoptosis seems to be mediated, in part, through the upregulation of the PPAR-γ and 15-LOX signaling pathways, with enhanced activation of caspase-3. Our findings support the future investigation of WTE as an antineoplastic and chemopreventive agent for lung cancer. Cancer Prev Res; 3(9); 1132–40. ©2010 AACR.
The Effect of Radial Velocity Gridding Artifacts on Variationally Retrieved Vertical Velocities
Authors: Collis Scott , Protat Alain , Chung Kao-Shen 
Published: July 2010

Abstract
This article investigates the source and impact of artifacts produced by ordered linear interpolation techniques on variationally retrieved updraft intensities. Qualitative reasoning for the generation of periodic perturbations in gridded products is presented, and a simple analytical investigation into the impact of gridding artifacts on updraft retrieval is carried out. By projecting a nonconvergent flow typical of Darwin, Australia, onto the viewing geometry of a scanning radar, a numerical assessment of the impact of gridding artifacts is carried out. A simple enhancement to ordered linear interpolation, mixed-order linear interpolation, is proposed to reduce gridding artifacts. Radial velocity grids produced using both techniques are used to investigate the generation of spurious updrafts, with the simple ordered linear interpolation technique producing erroneous updrafts on the order of 2 m s−1. To investigate the impact on vertical velocities retrieved from a real weather event, radar-derived measurements taken during the active monsoon phase of Tropical Warm Pool International Cloud Experiment are gridded using both techniques, and vertical velocities are retrieved and contrasted.
Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19
Authors: Kochenderfer James N. , Wilson Wyndham H. , Janik John E. , Dudley Mark E. , Stetler-Stevenson Maryalice , Feldman Steven A. , Maric Irina , Raffeld Mark , Nathan Debbie-Ann N. , Lanier Brock J. , Morgan Richard A. , Rosenberg Steven A. 
Published: July 2010

AbstractAdoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) that recognized the B-cell antigen CD19. The patient's lymphoma underwent a dramatic regression, and B-cell precursors were selectively eliminated from the patient's bone marrow after infusion of anti–CD19-CAR-transduced T cells. Blood B cells were absent for at least 39 weeks after anti–CD19-CAR-transduced T-cell infusion despite prompt recovery of other blood cell counts. Consistent with eradication of B-lineage cells, serum immunoglobulins decreased to very low levels after treatment. The prolonged and selective elimination of B-lineage cells could not be attributed to the chemotherapy that the patient received and indicated antigen-specific eradication of B-lineage cells. Adoptive transfer of anti–CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies. This study is registered at www.clinicaltrials.gov as #NCT00924326.
Differential behaviour of normal, transformed and Fanconi's anemia lymphoblastoid cells to modeled microgravity
Authors: Cuccarolo Paola , Barbieri Francesca , Sancandi Monica , Viaggi Silvia , Degan Paolo 
Published: July 2010

Abstract

Background
Whether microgravity might influence tumour growth and carcinogenesis is still an open issue. It is not clear also if and how normal and transformed cells are differently solicited by microgravity. The present study was designed to verify this issue.

Methods
Two normal, LB and HSC93, and two transformed, Jurkat and 1310, lymphoblast cell lines were used as representative for the two conditions. Two lymphoblast lines from Fanconi's anemia patients group A and C (FA-A and FA-C, respectively), along with their isogenic corrected counterparts (FA-A-cor and FA-C-cor) were also used. Cell lines were evaluated for their proliferative ability, vitality and apoptotic susceptibility upon microgravity exposure in comparison with unexposed cells. Different parameters correlated to energy metabolism, glucose consumption, mitochondrial membrane potential (MMP), intracellular ATP content, red-ox balance and ability of the cells to repair the DNA damage product 8-OHdG induced by the treatment of the cells with 20 mM KBrO3 were also evaluated.

Results
Transformed Jurkat and 1310 cells appear resistant to the microgravitational challenge. On the contrary normal LB and HSC93 cells display increased apoptotic susceptibility, shortage of energy storages and reduced ability to cope with oxidative stress. FA-A and FA-C cells appear resistant to microgravity exposure, analogously to transformed cells. FA corrected cells did shown intermediate sensitivity to microgravity exposure suggesting that genetic correction does not completely reverts cellular phenotype.

Conclusions
In the light of the reported results microgravity should be regarded as an harmful condition either when considering normal as well as transformed cells. Modeled microgravity and space-based technology are interesting tools in the biomedicine laboratory and offer an original, useful and unique approach in the study of cellular biochemistry and in the regulation of metabolic pathways.
Inference on population history and model checking using DNA sequence and microsatellite data with the software DIYABC (v1.0)
Authors: Cornuet Jean-Marie , Ravigné Virgine , Estoup Arnaud 
Published: July 2010

AbstractBackgroundApproximate Bayesian computation (ABC) is a recent flexible class of Monte-Carlo algorithms increasingly used to make model-based inference on complex evolutionary scenarios that have acted on natural populations. The software DIYABC offers a user-friendly interface allowing non-expert users to consider population histories involving any combination of population divergences, admixtures and population size changes. We here describe and illustrate new developments of this software that mainly include (i) inference from DNA sequence data in addition or separately to microsatellite data, (ii) the possibility to analyze five categories of loci considering balanced or non balanced sex ratios: autosomal diploid, autosomal haploid, X-linked, Y-linked and mitochondrial, and (iii) the possibility to perform model checking computation to assess the "goodness-of-fit" of a model, a feature of ABC analysis that has been so far neglected.ResultsWe used controlled simulated data sets generated under evolutionary scenarios involving various divergence and admixture events to evaluate the effect of mixing autosomal microsatellite, mtDNA and/or nuclear autosomal DNA sequence data on inferences. This evaluation included the comparison of competing scenarios and the quantification of their relative support, and the estimation of parameter posterior distributions under a given scenario. We also considered a set of scenarios often compared when making ABC inferences on the routes of introduction of invasive species to illustrate the interest of the new model checking option of DIYABC to assess model misfit.ConclusionsOur new developments of the integrated software DIYABC should be particularly useful to make inference on complex evolutionary scenarios involving both recent and ancient historical events and using various types of molecular markers in diploid or haploid organisms. They offer a handy way for non-expert users to achieve model checking computation within an ABC framework, hence filling up a gap of ABC analysis. The software DIYABC V1.0 is freely available athttp://www1.montpellier.inra.fr/CBGP/diyabc.
Comparative genome analysis of a large Dutch Legionella pneumophila strain collection identifies five markers highly correlated with clinical strains
Authors: Yzerman Ed , den Boer Jeroen W , Caspers Martien , Almal Arpit , Worzel Bill , van der Meer Walter , Montijn Roy , Schuren Frank 
Published: July 2010

Abstract

Background
Discrimination between clinical and environmental strains within many bacterial species is currently underexplored. Genomic analyses have clearly shown the enormous variability in genome composition between different strains of a bacterial species. In this study we have used Legionella pneumophila, the causative agent of Legionnaire's disease, to search for genomic markers related to pathogenicity. During a large surveillance study in The Netherlands well-characterized patient-derived strains and environmental strains were collected. We have used a mixed-genome microarray to perform comparative-genome analysis of 257 strains from this collection.

Results
Microarray analysis indicated that 480 DNA markers (out of in total 3360 markers) showed clear variation in presence between individual strains and these were therefore selected for further analysis. Unsupervised statistical analysis of these markers showed the enormous genomic variation within the species but did not show any correlation with a pathogenic phenotype. We therefore used supervised statistical analysis to identify discriminating markers. Genetic programming was used both to identify predictive markers and to define their interrelationships. A model consisting of five markers was developed that together correctly predicted 100% of the clinical strains and 69% of the environmental strains.

Conclusions
A novel approach for identifying predictive markers enabling discrimination between clinical and environmental isolates of L. pneumophila is presented. Out of over 3000 possible markers, five were selected that together enabled correct prediction of all the clinical strains included in this study. This novel approach for identifying predictive markers can be applied to all bacterial species, allowing for better discrimination between strains well equipped to cause human disease and relatively harmless strains.
Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus
Authors: Zhang Dongying , Efendic Suad , Brismar Kerstin , Gu Harvest F 
Published: July 2010

Abstract

Background

MCF2L2, ADIPOQ and SOX2 genes are located in chromosome 3q26-27, which is linked to diabetic nephropathy (DN). ADIPOQ and SOX2 genetic polymorphisms are found to be associated with DN. In the present study, we first investigated the association between MCF2L2 and DN, and then evaluated effects of these three genes on the development of DN.

Methods
A total of 1177 type 1 diabetes patients with and without DN from the GoKinD study were genotyped with TaqMan allelic discrimination. All subjects were of European descent.

Results
Leu359Ile T/G variant in the MCF2L2 gene was found to be associated with DN in female subjects (P = 0.017, OR = 0.701, 95%CI 0.524-0.938) but not in males. The GG genotype carriers among female patients with DN had tendency decreased creatinine and cystatin levels compared to the carriers with either TT or TG genotypes. This polymorphism MCF2L2-rs7639705 together with SNPs of ADIPOQ-rs266729 and SOX2-rs11915160 had combined effects on decreased risk of DN in females (P = 0.001).

Conclusion
The present study provides evidence that MCF2L2, ADIPOQ and SOX2 genetic polymorphisms have effects on the resistance of DN in female T1D patients, and suggests that the linkage with DN in chromosome 3q may be explained by the cumulated genetic effects.
The relationship between staff skill mix, costs and outcomes in intermediate care services
Authors: Dixon Simon , Kaambwa Billingsley , Nancarrow Susan , Martin Graham P , Bryan Stirling 
Published: July 2010

AbstractBackgroundThe purpose of this study was to assess the relationship between skill mix, patient outcomes, length of stay and service costs in older peoples' intermediate care services in England.MethodsWe undertook multivariate analysis of data collected as part of the National Evaluation of Intermediate Care Services. Data were analysed on between 337 and 403 older people admitted to 14 different intermediate care teams. Independent variables were the numbers of different types of staff within a team and the ratio of support staff to professionally qualified staff within teams. Outcome measures include the Barthel index, EQ-5D, length of service provision and costs of care.ResultsIncreased skill mix (raising the number of different types of staff by one) is associated with a 17% reduction in service costs (p = 0.011). There is weak evidence (p = 0.090) that a higher ratio of support staff to qualified staff leads to greater improvements in EQ-5D scores of patients.ConclusionsThis study provides limited evidence on the relationship between multidisciplinary skill mix and outcomes in intermediate care services.
Low temperature of radiofrequency ablation at the target sites can facilitate rapid progression of residual hepatic VX2 carcinoma
Authors: Ke Shan , Ding Xue-mei , Kong Jian , Gao Jun , Wang Shao-hong , Cheng Yan , Sun Wen-bing 
Published: July 2010

Abstract

Background
Rapid progression of residual tumor after radiofrequency ablation (RFA) of hepatocellular carcinoma has been observed increasingly. However, its underlying mechanisms remain to be clarified. The present study was designed to determine whether low temperature of RFA at the target sites facilitates rapid progression of residual hepatic VX2 carcinoma and to clarify the possible underlying mechanisms.

Methods
The residual VX2 hepatoma model in rabbits was established by using RFA at 55, 70 and 85°C. Rabbits that were implanted with VX2 hepatoma but did not receive RFA acted as a control group. The relationship between rapid progression of residual hepatic VX2 carcinoma and low temperature of RFA at the target sites was carefully evaluated. A number of potential contributing molecular factors, such as proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and Interleukin-6 (IL-6) were measured.

Results
The focal tumor volume and lung metastases of RFA-treated rabbits increased significantly compared with the control group (P < 0.05), and the greatest changes were seen in the 55°C group (P < 0.05). Expression of PCNA, MMP-9, VEGF, HGF and IL-6 in tumor tissues increased significantly in the RFA-treated groups compared with the control group, and of the increases were greatest in the 55°C group (P < 0.05). These results were consistent with gross pathological observation. Tumor re-inoculation experiments confirmed that low temperature of RFA at the target sites facilitated rapid progression of residual hepatic VX2 carcinoma.

Conclusions
Insufficient RFA that is caused by low temperature at the target sites could be an important cause of rapid progression of residual hepatic VX2 carcinoma. Residual hepatic VX2 carcinoma could facilitate its rapid progression through inducing overexpression of several molecular factors, such as PCNA, MMP-9, VEGF, HGF and IL-6.
An H5N1 M2e-based multiple antigenic peptide vaccine confers heterosubtypic protection from lethal infection with pandemic 2009 H1N1 virus
Authors: Zhao Guangyu , Sun Shihui , Du Lanying , Xiao Wenjun , Ru Zhitao , Kou Zhihua , Guo Yan , Yu Hong , Jiang Shibo , Lone Yuchun , Zheng Bo-Jian , Zhou Yusen 
Published: July 2010

Abstract

Background
A 2009 global influenza pandemic caused by a novel swine-origin H1N1 influenza A virus has posted an increasing threat of a potential pandemic by the highly pathogenic avian influenza (HPAI) H5N1 virus, driving us to develop an influenza vaccine which confers cross-protection against both H5N1 and H1N1 viruses. Previously, we have shown that a tetra-branched multiple antigenic peptide (MAP) vaccine based on the extracellular domain of M2 protein (M2e) from H5N1 virus (H5N1-M2e-MAP) induced strong immune responses and cross-protection against different clades of HPAI H5N1 viruses. In this report, we investigated whether such M2e-MAP presenting the H5N1-M2e consensus sequence can afford heterosubtypic protection from lethal challenge with the pandemic 2009 H1N1 virus.

Results
Our results demonstrated that H5N1-M2e-MAP plus Freund's or aluminum adjuvant induced strong cross-reactive IgG antibody responses against M2e of the pandemic H1N1 virus which contains one amino acid variation with M2e of H5N1 at position 13. These cross-reactive antibodies may maintain for 6 months and bounced back quickly to the previous high level after the 2nd boost administered 2 weeks before virus challenge. H5N1-M2e-MAP could afford heterosubtypic protection against lethal challenge with pandemic H1N1 virus, showing significant decrease of viral replications and obvious alleviation of histopathological damages in the challenged mouse lungs. 100% and 80% of the H5N1-M2e-MAP-vaccinated mice with Freund's and aluminum adjuvant, respectively, survived the lethal challenge with pandemic H1N1 virus.

Conclusions
Our results suggest that H5N1-M2e-MAP has a great potential to prevent the threat from re-emergence of pandemic H1N1 influenza and possible novel influenza pandemic due to the reassortment of HPAI H5N1 virus with the 2009 swine-origin H1N1 influenza virus.