bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diffuse large B-cell lymphoma: reduced CD20 expression is associated with an inferior survival
Authors: Johnson Nathalie A. , Boyle Merrill , Bashashati Ali , Leach Stephen , Brooks-Wilson Angela , Sehn Laurie H. , Chhanabhai Mukesh , Brinkman Ryan R. , Connors Joseph M. , Weng Andrew P. , Gascoyne Randy D. 
Published: November 2008

AbstractCD19 and CD20 are B cell–specific antigens whose expression is heterogeneous when analyzed by flow cytometry (FCM). We determined the association between CD20 expression and clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL). The mean fluorescence intensity of CD20 and CD19 was determined by FCM, and the cytoplasmic expression of CD20 was determined by immunohistochemistry (IHC) on 272 diagnostic DLBCL samples. Exon 5 of the MS4A1 gene coding for the extracellular component of the CD20 antigen was sequenced in 15 samples. A total of 43 of 272 (16%) samples had reduced CD20 expression by FCM; of these, 35 (13%) had bright CD19 expression. The latter had a markedly inferior survival when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP (R-CHOP; median survival of 1.2 and 3.0 years vs not reached for the others, P < .001 and P = .001), independent of the International Prognostic Index. A total of 41 of 43 samples with reduced CD20 expression by FCM had strong staining for CD20 by IHC. There were no mutations in exon 5 of the MS4A1 gene to explain the discrepancy between FCM and IHC. CD20 and CD19 expression by FCM should be determined on all biopsies of patients with DLBCL because reduced CD20 expression cannot be reliably detected by IHC.
Lipid bilayer composition influences small multidrug transporters
Authors: Charalambous Kalypso , Miller David , Curnow Paul , Booth Paula J 
Published: November 2008

Abstract

Background
Membrane proteins are influenced by their surrounding lipids. We investigate the effect of bilayer composition on the membrane transport activity of two members of the small multidrug resistance family; the Escherichia coli transporter, EmrE and the Mycobacterium tuberculosis, TBsmr. In particular we address the influence of phosphatidylethanolamine and anionic lipids on the activity of these multidrug transporters. Phosphatidylethanolamine lipids are native to the membranes of both transporters and also alter the lateral pressure profile of a lipid bilayer. Lipid bilayer lateral pressures affect membrane protein insertion, folding and activity and have been shown to influence reconstitution, topology and activity of membrane transport proteins.

Results
Both EmrE and TBsmr are found to exhibit a similar dependence on lipid composition, with phosphatidylethanolamine increasing methyl viologen transport. Anionic lipids also increase transport for both EmrE and TBsmr, with the proteins showing a preference for their most prevalent native anionic lipid headgroup; phosphatidylglycerol for EmrE and phosphatidylinositol for TBsmr.

Conclusion
These findings show that the physical state of the membrane modifies drug transport and that substrate translocation is dependent on in vitro lipid composition. Multidrug transport activity seems to respond to alterations in the lateral forces exerted upon the transport proteins by the bilayer.
EMAAS: An extensible grid-based Rich Internet Application for microarray data analysis and management
Authors: Barton G , Abbott J , Chiba N , Huang DW , Huang Y , Krznaric M , Mack-Smith J , Saleem A , Sherman BT , Tiwari B , Tomlinson C , Aitman T , Darlington J , Game L , Sternberg MJE , Butcher SA 
Published: November 2008

Abstract

Background
Microarray experimentation requires the application of complex analysis methods as well as the use of non-trivial computer technologies to manage the resultant large data sets. This, together with the proliferation of tools and techniques for microarray data analysis, makes it very challenging for a laboratory scientist to keep up-to-date with the latest developments in this field. Our aim was to develop a distributed e-support system for microarray data analysis and management.

Results
EMAAS (Extensible MicroArray Analysis System) is a multi-user rich internet application (RIA) providing simple, robust access to up-to-date resources for microarray data storage and analysis, combined with integrated tools to optimise real time user support and training. The system leverages the power of distributed computing to perform microarray analyses, and provides seamless access to resources located at various remote facilities. The EMAAS framework allows users to import microarray data from several sources to an underlying database, to pre-process, quality assess and analyse the data, to perform functional analyses, and to track data analysis steps, all through a single easy to use web portal. This interface offers distance support to users both in the form of video tutorials and via live screen feeds using the web conferencing tool EVO. A number of analysis packages, including R-Bioconductor and Affymetrix Power Tools have been integrated on the server side and are available programmatically through the Postgres-PLR library or on grid compute clusters. Integrated distributed resources include the functional annotation tool DAVID, GeneCards and the microarray data repositories GEO, CELSIUS and MiMiR. EMAAS currently supports analysis of Affymetrix 3' and Exon expression arrays, and the system is extensible to cater for other microarray and transcriptomic platforms.

Conclusion
EMAAS enables users to track and perform microarray data management and analysis tasks through a single easy-to-use web application. The system architecture is flexible and scalable to allow new array types, analysis algorithms and tools to be added with relative ease and to cope with large increases in data volume.
Tripeptide tyroserleutide plus doxorubicin: therapeutic synergy and side effect attenuation
Authors: Zhu Zhi-feng , Chen Li-juan , Lu Rong , Jia Jing , Liang Yu , Xu Qiong , Zhou Chun-lei , Wang Li , Wang Song , Yao Zhi 
Published: November 2008

Abstract

Background
Tripeptide tyroserleutide (YSL) is a novel small molecule anti-tumor polypeptide that has been shown to inhibit the growth of human liver cancer cells. In this study, we investigated the effects of YSL plus doxorubicin on the growth of human hepatocellular carcinoma BEL-7402 cells that had been transplanted into nude mice.

Methods
Nude mice bearing human hepatocellular carcinoma BEL-7402 tumors were treated with successive intraperitoneal injections of saline; low-, mid-, or high-dose doxorubicin; or low-, mid-, or high-dose doxorubicin plus YSL. Effects on the weight and volume of the tumors were evaluated.

Results
Co-administration of YSL and high-dose doxorubicin (6 mg/kg every other day) prolonged the survival time of tumor-bearing mice as compared to high-dose doxorubicin alone. As well, the anti-tumor effects of mid- and low-dose doxorubicin (2 and 0.7 mg/kg every other day, respectively) were enhanced when supplemented with YSL; the tumor growth inhibition rates for YSL plus doxorubicin were greater than the inhibition rates for the same dosages of doxorubicin alone. The combination of YSL and doxorubicin decreased chemotherapy-associated weight loss, leukocyte depression, and heart, liver, and kidney damage as compared to doxorubicin alone.

Conclusion
The combination of YSL plus doxorubicin enhances the anti-tumor effect and reduces the side effects associated with doxorubicin chemotherapy.
Gene expression variation between distinct areas of breast cancer measured from paraffin-embedded tissue cores
Authors: Schobesberger Martina , Baltzer Anna , Oberli Andrea , Kappeler Andreas , Gugger Mathias , Burger Hana , Jaggi Rolf 
Published: November 2008

Abstract

Background
Diagnosis and prognosis in breast cancer are mainly based on histology and immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) material. Recently, gene expression analysis was shown to elucidate the biological variance between tumors and molecular markers were identified that led to new classification systems that provided better prognostic and predictive parameters. Archived FFPE samples represent an ideal source of tissue for translational research, as millions of tissue blocks exist from routine diagnostics and from clinical studies. These should be exploited to provide clinicians with more accurate prognostic and predictive information. Unfortunately, RNA derived from FFPE material is partially degraded and chemically modified and reliable gene expression measurement has only become successful after implementing novel and optimized procedures for RNA isolation, demodification and detection.

Methods
In this study we used tissue cylinders as known from the construction of tissue microarrays. RNA was isolated with a robust protocol recently developed for RNA derived from FFPE material. Gene expression was measured by quantitative reverse transcription PCR.

Results
Sixteen tissue blocks from 7 patients diagnosed with multiple histological subtypes of breast cancer were available for this study. After verification of appropriate localization, sufficient RNA yield and quality, 30 tissue cores were available for gene expression measurement on TaqMan® Low Density Arrays (16 invasive ductal carcinoma (IDC), 8 ductal carcinoma in situ (DCIS) and 6 normal tissue), and 14 tissue cores were lost. Gene expression values were used to calculate scores representing the proliferation status (PRO), the estrogen receptor status and the HER2 status. The PRO scores measured from entire sections were similar to PRO scores determined from IDC tissue cores. Scores determined from normal tissue cores consistently revealed lower PRO scores than cores derived from IDC or DCIS of the same block or from different blocks of the same patient.

Conclusion
We have developed optimized protocols for RNA isolation from histologically distinct areas. RNA prepared from FFPE tissue cores is suitable for gene expression measurement by quantitative PCR. Distinct molecular scores could be determined from different cores of the same tumor specimen.
The complicated management of a patient following transarterial chemoembolization for metastatic carcinoid
Authors: Pearson Andrew C , Steinberg Steven , Shah Manisha H , Bloomston Mark 
Published: November 2008

Abstract

Background
Transarterial Chemoembolization (TACE) has been recognized as a successful way of managing symptomatic and/or progressive hepatic carcinoid metastases not amenable to surgical resection. Although it is a fairly safe procedure, it is not without its complications.

Case presentation
This is a case of a 53 year-old woman with a patent foramen ovale (PFO) and mild pulmonary hypertension who underwent TACE for progressive carcinoid liver metastases. She developed acute heart failure, due to a severe inflammatory response; this resulted in pneumatosis intestinalis due to non-occlusive mesenteric ischemia. We describe the successful non-operative management of her pneumatosis intestinalis and the role of a PFO in this patient's heart failure.

Conclusion
TACE remains an effective and safe treatment for metastatic carcinoid not amenable to resection, this case illustrates the complexity of complications that can arise. A multi-disciplinary approach including ready access to advanced critical care facilities is recommended in managing such complex patients.
Assessing the clinical utility of measuring Insulin-like Growth Factor Binding Proteins in tissues and sera of melanoma patients
Authors: Yu Jessie Z , Warycha Melanie A , Christos Paul J , Darvishian Farbod , Yee Herman , Kaminio Hideko , Berman Russell S , Shapiro Richard L , Buckley Michael T , Liebes Leonard F , Pavlick Anna C , Polsky David , Brooks Peter C , Osman Iman 
Published: November 2008

Abstract

Background
Different Insulin-like Growth Factor Binding Proteins (IGFBPs) have been investigated as potential biomarkers in several types of tumors. In this study, we examined both IGFBP-3 and -4 levels in tissues and sera of melanoma patients representing different stages of melanoma progression.

Methods
The study cohort consisted of 132 melanoma patients (primary, n = 72; metastatic, n = 60; 64 Male, 68 Female; Median Age = 56) prospectively enrolled in the New York University School of Medicine Interdisciplinary Melanoma Cooperative Group (NYU IMCG) between August 2002 and December 2006. We assessed tumor-expression and circulating sera levels of IGFBP-3 and -4 using immunohistochemistry and ELISA assays. Correlations with clinicopathologic parameters were examined using Wilcoxon rank-sum tests and Spearman-rank correlation coefficients.

Results
Median IGFBP-4 tumor expression was significantly greater in primary versus metastatic patients (70% versus 10%, p = 0.01) A trend for greater median IGFBP-3 sera concentration was observed in metastatic versus primary patients (4.9 μg/ml vs. 3.4 μg/ml, respectively, p = 0.09). However, sera levels fell within a normal range for IGFBP-3. Neither IGFBP-3 nor -4 correlated with survival in this subset of patients.

Conclusion
Decreased IGFBP-4 tumor expression might be a step in the progression from primary to metastatic melanoma. Our data lend support to a recently-described novel tumor suppressor role of secreting IGFBPs in melanoma. However, data do not support the clinical utility of measuring levels of IGFBP-3 and -4 in sera of melanoma patients.
Identification of possible candidate genes regulating Sjögren's syndrome-associated autoimmunity: a potential role for TNFSF4in autoimmune exocrinopathy
Authors: Nguyen Cuong Q , Cornelius Janet G , Cooper Lauren , Neff Jonathan , Tao Joann , Lee Byung Ha , Peck Ammon B 
Published: November 2008

Abstract
Introduction
Sjögren syndrome (SjS) is a systemic autoimmune disease in which an immunological attack primarily against the salivary and lacrimal glands results in the loss of acinar cell tissue and function, leading to stomatitis sicca and keratoconjunctivitis sicca. In recent years, two genetic regions, one on chromosome 1 (designated autoimmune exocrinopathy 2 or Aec2) and the second on chromosome 3 (designated autoimmune exocrinopathy 1 or Aec1) derived from nonobese diabetic (NOD) mice, have been shown to be necessary and sufficient to replicate SjS-like disease in nonsusceptible C57BL/6 mice.

Methods
Starting with the SjS-susceptible C57BL/6-derived mouse, referred to as C57BL/6.NOD-Aec1Aec2, we generated a large set of recombinant inbred (RI) lines containing portions of Aec2 as a means of identifying more precisely the genetic elements of chromosome 1 responsible for disease development.

Results
Disease profiling of these RI lines has revealed that the SjS susceptibility genes of Aec2 lie within a region located at approximately 79 ± 5 cM distal to the centromere, as defined by microsatellite markers. This chromosomal region contains several sets of genes known to correlate with various immunopathological features of SjS as well as disease susceptibility genes for both type 1 diabetes and systemic lupus erythematosus in mice. One gene in particular, tumor necrosis factor (ligand) superfamily member 4 (or Ox40 ligand), encoding a product whose biological functions correlate with both physiological homeostasis and immune regulations, could be a potential candidate SjS susceptibility gene.

Conclusions
These new RI lines represent the first step not only in fine mapping SjS susceptibility loci but also in identifying potential candidate SjS susceptibility genes. Identification of possible candidate genes permits construction of models describing underlying molecular pathogenic mechanisms in this model of SjS and establishes a basis for construction of specific gene knockout mice.
Phase I Trial of Interleukin-12 Plasmid Electroporation in Patients With Metastatic Melanoma
Authors: Daud Adil I. , DeConti Ronald C. , Andrews Stephanie , Urbas Patricia , Riker Adam I. , Sondak Vernon K. , Munster Pamela N. , Sullivan Daniel M. , Ugen Kenneth E. , Messina Jane L. , Heller Richard 
Published: November 2008

Purpose Gene-based immunotherapy for cancer is limited by the lack of safe, efficient, reproducible, and titratable delivery methods. Direct injection of DNA into tissue, although safer than viral vectors, suffers from low gene transfer efficiency. In vivo electroporation, in preclinical models, significantly enhances gene transfer efficiency while retaining the safety advantages of plasmid DNA. Patients and Methods A phase I dose escalation trial of plasmid interleukin (IL)-12 electroporation was carried out in patients with metastatic melanoma. Patients received electroporation on days 1, 5, and 8 during a single 39-day cycle, into metastatic melanoma lesions with six 100-μs pulses at a 1,300-V/cm electric field through a penetrating six-electrode array immediately after DNA injection. Pre- and post-treatment biopsies were obtained at defined time points for detailed histologic evaluation and determination of IL-12 protein levels. Results Twenty-four patients were treated at seven dose levels, with minimal systemic toxicity. Transient pain after electroporation was the major adverse effect. Post-treatment biopsies showed plasmid dose proportional increases in IL-12 protein levels as well as marked tumor necrosis and lymphocytic infiltrate. Two (10%) of 19 patients with nonelectroporated distant lesions and no other systemic therapy showed complete regression of all metastases, whereas eight additional patients (42%) showed disease stabilization or partial response. Conclusion This report describes the first human trial, to our knowledge, of gene transfer utilizing in vivo DNA electroporation. The results indicated this modality to be safe, effective, reproducible, and titratable.
Self-Reported Practices and Attitudes of US Oncologists Regarding Off-Protocol Therapy
Authors: Peppercorn Jeffrey , Burstein Harold , Miller Franklin G. , Winer Eric , Joffe Steve 
Published: November 2008

Purpose Investigational cancer therapies being tested in clinical trials may be available outside of trials, or off-protocol (OPRx). We evaluated the practices and attitudes among US oncologists with regard to this controversial practice. Methods We mailed an anonymous survey to a random sample of US medical oncologists evaluating frequency and prevalence of OPRx and evaluated the correlation between demographic factors, attitudes, and practice. Results One hundred forty-six (31%) of 471 oncologists responded. Ninety-three percent reported ever discussing and 81% ever prescribing OPRx. Academic oncologists were more likely than community oncologists to have ever provided OPRx (89% v 75%; P = .06), to discuss OPRx at least once/month (41% v 19%; P = .0004), and to deny requests for OPRx at least once/month (16% v 2%; P = .004). While 61% of oncologists believed that patients should be discouraged from OPRx, only 31% felt it should not be available. With regard to trial recruitment, 53% felt that informed consent requires discussion of OPRx, 34% disagree, and 26% feel that patients should be provided OPRx on request, while 56% disagree. There was lack of consensus on access to OPRx in scenarios based on open trials at the time of the survey, such as adjuvant trastuzumab, which 41% would provide, 59% would not. Conclusion US oncologists report common discussion and use of OPRx, but attitudes and practices may vary substantially. There is need for greater debate regarding OPRx in oncology, further definition of the ethical and clinical issues at stake, and development of guidelines in this area.
The effect of axial charge stratification and exhaust gases on combustion ‘development’ in a homogeneous charge compression ignition engine
Authors: Aleiferis P G , Charalambides A G , Hardalupas Y , Taylor A M K P , Urata Y 
Published: November 2008

A high-swirl low-compression-ratio, optically accessed engine that was able to produce a stratified charge was used to investigate the differences in homogeneous charge compression ignition (HCCI) combustion and in the propagation of the autoignition front between a non-stratified and a stratified charge. Natural-light images were acquired using a fast camera to visualize HCCI combustion and to quantify the location of autoignition, the apparent ‘propagation speed’ of the autoignition front, and its variations between closed-valve injection timing (leading to a nearly homogeneous charge) and open-valve injection timing (leading to a strongly axially stratified charge), owing to temperature inhomogeneities that were introduced by utilizing a camshaft which allowed 40 per cent internal exhaust gas recirculation (iEGR). Experimental results show that, in the case without exhaust gas recirculation (EGR) and with closed-valve injection timing, autoignition started under the primary intake valve near the cylinder wall, while, in the case without EGR and with open-valve injection timing, autoignition started between the exhaust valve and the secondary intake valve, closer to the centre of the piston. With 40 per cent iEGR and closed-valve injection timing, autoignition started between the exhaust valve and the primary intake valve near the cylinder wall. These differences can be explained by the difference in the location of hot gases due to the injection timing or due to iEGR. Finally, without EGR, a ‘uniform’ autoignition front of HCCI combustion from the original sites of autoignition was observed compared with a more ‘random development’ of the autoignition front with 40 per cent iEGR. Strong local inhomogeneities (possibly a very rich mixture at a low temperature) could be present with 40 per cent iEGR.
Experimental investigation of combustion and heat transfer in a direct-injection spark ignition engine via instantaneous combustion chamber surface temperature measurements
Authors: Cho K-W , Assanis D , Filipi Z , Szekely G , Najt P , Rask R 
Published: November 2008

An experimental study was performed to provide the combustion and in-cylinder heat transfer characteristics resulting from different injection strategies in a direct-injection spark ignition (DISI) engine. Fast-response thermocouples were embedded in the piston top and cylinder head surface to measure the instantaneous combustion chamber surface temperature and heat flux, thus providing critical information about the combustion characteristics and a thorough understanding of the heat transfer process. Two distinctive operating modes, homogeneous and stratified, were considered and their effect on combustion and heat transfer in a DISI engine was investigated. The stratified operating mode yielded significantly higher spatial variations of heat flux than the homogeneous mode. This behaviour is directly caused by the main features of stratified combustion, i.e. vigorous burning of a close-to-stoichiometric mixture near the spark, and a cool, extremely lean mixture at the periphery. The cooling effect of the spray impinging on the piston surface when the fuel is injected late in compression could be detected too. The local phenomena change with varying speed and injection parameters. Comparison between the calculated global heat fluxes and measured local heat fluxes were performed in order to assess the behaviour of classic heat transfer models. Comparisons between the global and local heat fluxes provide additional insight into spatial variations, as well as indications about the suitability of different classic models for investigations of the heat transfer aspect of DISI engines. Special consideration is required when applying classic heat transfer correlations to stratified DISI operation as heat flux values are lower by more than 30 per cent when compared with homogeneous operation of the same engine at the same load.