bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-level expression of HER2 and CK19 in normal peripheral blood mononuclear cells: relevance for detection of circulating tumor cells
Authors: You Fanglei , Roberts Lisa A , Kang S Peter , Nunes Raquel A , Dias Cinara , Iglehart J Dirk , Solomon Natalie A , Friedman Paula N , Harris Lyndsay N 
Published: May 2008

Abstract

Background
Detection of circulating tumor cells (CTC) in the blood of cancer patients may have prognostic and predictive significance. However, background expression of 'tumor specific markers' in peripheral blood mononuclear cells (PBMC) may confound these studies. The goal of this study was to identify the origin of Cytokeratin 19 (CK19) and HER-2 signal in PBMC and suggest an approach to enhance techniques involved in detection of CTC in breast cancer patients.

Methods
PBMC from healthy donors were isolated and fractionated into monocytes, lymphocytes, natural killer cells/granulocytes and epithelial populations using immunomagnetic selection and fluorescent cell-sorting for each cell type. RNA isolated from each fraction was analyzed for CK19, HER2 and Beta 2 microglobulin (B2M) using real-time qRT-PCR. Positive selection for epithelial cells and negative selection for NK/granulocytes were used in an attempt to reduce background expression of CK19 and HER2 markers.

Results
In normal PBMC, CK19 was expressed in the lymphocyte population while HER-2 expression was highest in the NK/granulocyte population. Immunomagnetic selection for epithelial cells reduced background CK19 signal to a frequency of <5% in normal donors. Using negative selection, the majority (74–98%) of HER2 signal could be removed from PBMC. Positive selection methods are variably effective at reducing these background signals.

Conclusion
We present a novel method to improve the specificity of the traditional method of detecting CTC by identifying the source of the background signals and reducing them by negative immunoselection. Further studies are warranted to improve sensitivity and specificity of methods of detecting CTC will prove to be useful tools for clinicians in determining prognosis and monitoring treatment responses of breast cancer patients.
Effects of common germline genetic variation in cell cycle control genes on breast cancer survival: results from a population-based cohort
Authors: Azzato Elizabeth M , Driver Kristy E , Lesueur Fabienne , Shah Mitul , Greenberg David , Easton Douglas F , Teschendorff Andrew E , Caldas Carlos , Caporaso Neil E , Pharoah Paul DP 
Published: May 2008

Abstract
Introduction
Somatic alterations have been shown to correlate with breast cancer prognosis and survival, but less is known about the effects of common inherited genetic variation. Of particular interest are genes involved in cell cycle pathways, which regulate cell division.

Methods
We examined associations between common germline genetic variation in 13 genes involved in cell cycle control (CCND1, CCND2, CCND3, CCNE1, CDK2 [p33], CDK4, CDK6, CDKN1A [p21, Cip1], CDKN1B [p27, Kip1], CDKN2A [p16], CDKN2B [p15], CDKN2C [p18], and CDKN2D [p19]) and survival among women diagnosed with invasive breast cancer participating in the SEARCH (Studies of Epidemiology and Risk factors in Cancer Heredity) breast cancer study. DNA from up to 4,470 women was genotyped for 85 polymorphisms that tag the known common polymorphisms (minor allele frequency > 0.05) in the genes. The genotypes of each polymorphism were tested for association with survival using Cox regression analysis.

Results
The rare allele of the tagging single nucleotide polymorphism (SNP) rs2479717 is associated with an increased risk of death (hazard ratio = 1.26 per rare allele carried, 95% confidence interval: 1.12 to 1.42; P = 0.0001), which was not attenuated after adjusting for tumour stage, grade, and treatment. This SNP is part of a large linkage disequilibrium block, which contains CCND3, BYSL, TRFP, USP49, C6ofr49, FRS3, and PGC. We evaluated the association of survival and somatic expression of these genes in breast tumours using expression microarray data from seven published datasets. Elevated expression of the C6orf49 transcript was associated with breast cancer survival, adding biological interest to the finding.

Conclusion
It is possible that CCND3 rs2479717, or another variant it tags, is associated with prognosis after a diagnosis of breast cancer. Further study is required to validate this finding.
Calling on a million minds for community annotation in WikiProteins
Authors: Mons Barend , Ashburner Michael , Chichester Christine , van Mulligen Erik , Weeber Marc , den Dunnen Johan , van Ommen Gert-Jan , Musen Mark , Cockerill Matthew , Hermjakob Henning , Mons Albert , Packer Abel , Pacheco Roberto , Lewis Suzanna , Berkeley Alfred , Melton William , Barris Nickolas , Wales Jimmy , Meijssen Gerard , Moeller Erik , Roes Peter Jan , Borner Katy , Bairoch Amos 
Published: May 2008

AbstractWikiProteins enables community annotation in a Wiki-based system. Extracts of major data sources have been fused into an editable environment that links out to the original sources. Data from community edits create automatic copies of the original data. Semantic technology captures concepts co-occurring in one sentence and thus potential factual statements. In addition, indirect associations between concepts have been calculated. We call on a 'million minds' to annotate a 'million concepts' and to collect facts from the literature with the reward of collaborative knowledge discovery. The system is available for beta testing at http://www.wikiprofessional.org.
Unraveling the genomic mosaic of a ubiquitous genus of marine cyanobacteria
Authors: Dufresne Alexis , Ostrowski Martin , Scanlan David J , Garczarek Laurence , Mazard Sophie , Palenik Brian P , Paulsen Ian T , de Marsac Nicole Tandeau , Wincker Patrick , Dossat Carole , Ferriera Steve , Johnson Justin , Post Anton F , Hess Wolfgang R , Partensky Frédéric 
Published: May 2008

Abstract
Background
The picocyanobacterial genus Synechococcus occurs over wide oceanic expanses, having colonized most available niches in the photic zone. Large scale distribution patterns of the different Synechococcus clades (based on 16S rRNA gene markers) suggest the occurrence of two major lifestyles ('opportunists'/'specialists'), corresponding to two distinct broad habitats ('coastal'/'open ocean'). Yet, the genetic basis of niche partitioning is still poorly understood in this ecologically important group.

Results
Here, we compare the genomes of 11 marine Synechococcus isolates, representing 10 distinct lineages. Phylogenies inferred from the core genome allowed us to refine the taxonomic relationships between clades by revealing a clear dichotomy within the main subcluster, reminiscent of the two aforementioned lifestyles. Genome size is strongly correlated with the cumulative lengths of hypervariable regions (or 'islands'). One of these, encompassing most genes encoding the light-harvesting phycobilisome rod complexes, is involved in adaptation to changes in light quality and has clearly been transferred between members of different Synechococcus lineages. Furthermore, we observed that two strains (RS9917 and WH5701) that have similar pigmentation and physiology have an unusually high number of genes in common, given their phylogenetic distance.

Conclusion
We propose that while members of a given marine Synechococcus lineage may have the same broad geographical distribution, local niche occupancy is facilitated by lateral gene transfers, a process in which genomic islands play a key role as a repository for transferred genes. Our work also highlights the need for developing picocyanobacterial systematics based on genome-derived parameters combined with ecological and physiological data.
Dynamic instability of the major urinary protein gene family revealed by genomic and phenotypic comparisons between C57 and 129 strain mice
Authors: Mudge Jonathan M , Armstrong Stuart D , McLaren Karen , Beynon Robert J , Hurst Jane L , Nicholson Christine , Robertson Duncan H , Wilming Laurens G , Harrow Jennifer L 
Published: May 2008

Abstract
Background
The major urinary proteins (MUPs) of Mus musculus domesticus are deposited in urine in large quantities, where they bind and release pheromones and also provide an individual 'recognition signal' via their phenotypic polymorphism. Whilst important information about MUP functionality has been gained in recent years, the gene cluster is poorly studied in terms of structure, genic polymorphism and evolution.

Results
We combine targeted sequencing, manual genome annotation and phylogenetic analysis to compare the Mup clusters of C57BL/6J and 129 strains of mice. We describe organizational heterogeneity within both clusters: a central array of cassettes containing Mup genes highly similar at the protein level, flanked by regions containing Mup genes displaying significantly elevated divergence. Observed genomic rearrangements in all regions have likely been mediated by endogenous retroviral elements. Mup loci with coding sequences that differ between the strains are identified - including a gene/pseudogene pair - suggesting that these inbred lineages exhibit variation that exists in wild populations. We have characterized the distinct MUP profiles in the urine of both strains by mass spectrometry. The total MUP phenotype data is reconciled with our genomic sequence data, matching all proteins identified in urine to annotated genes.

Conclusion
Our observations indicate that the MUP phenotypic polymorphism observed in wild populations results from a combination of Mup gene turnover coupled with currently unidentified mechanisms regulating gene expression patterns. We propose that the structural heterogeneity described within the cluster reflects functional divergence within the Mup gene family.
Prevalence and Treatment Patterns of Physical Impairments in Patients With Metastatic Breast Cancer
Authors: Cheville Andrea L. , Troxel Andrea B. , Basford Jeffrey R. , Kornblith Alice B. 
Published: May 2008

Purpose Physical impairments cause profound functional declines in patients with cancer. Although common rehabilitation measures can address many impairments, the extent of their delivery is unknown. We studied these issues by quantifying physical impairments in patients with metastatic breast cancer and by assessing how they are addressed. Patients and Methods A consecutive sample of 163 community-dwelling patients with metastatic breast cancer was stratified by Karnofsky performance score and administered the Medical Outcomes Study Physical Function Subscale and the Older Americans Resource Study Activities of Daily Living subscales. Cancer-related physical impairments were identified through a physical examination, the 6-Minute Walk Test, and the Functional Independence Measure Mobility Subscale. Patients were questioned regarding the nature, type, and setting of treatments for impairments. Physical rehabilitation needs were determined through a consensus process involving physiatrists and physical/occupational therapists specializing in cancer. Results Ninety-two percent of patients (150 of 163) had at least one physical impairment. Among 530 identified impairments, 484 (92%) required a physical rehabilitation intervention and 469 (88%) required physical therapy (PT) and/or occupational therapy (OT). Only 30% of impairments requiring rehabilitation services and 21% of those requiring PT/OT received treatment. Impairments detected during hospitalization were overwhelmingly more likely to receive a rehabilitation intervention (odds ratio [OR] = 87.9; 95% CI, 28.5 to 271.4), and PT/OT (OR = 558.8; 95% CI, 187.0 to 1,669.6). Low socioeconomic and minority status were significantly associated with nontreatment. Conclusion Remediable physical impairments were prevalent and poorly addressed among patients with metastatic breast cancer, drastically so in the outpatient setting. Undertreatment was particularly prominent among minority and socioeconomically disadvantaged groups.
Quality of Life Scores Predict Survival Among Patients With Head and Neck Cancer
Authors: Karvonen-Gutierrez Carrie A. , Ronis David L. , Fowler Karen E. , Terrell Jeffrey E. , Gruber Stephen B. , Duffy Sonia A. 
Published: May 2008

Purpose The purpose of this study was to examine whether quality of life (QOL) scores predict survival among patients with head and neck cancer, controlling for demographic, health behavior, and clinical variables. Patients and Methods A self-administered questionnaire was given to 495 patients being treated for head and neck cancer while they were waiting to be seen for a clinic appointment. Data collected from the survey included demographics, health behaviors, and QOL as measured by Short Form-36 (SF-36) physical and mental component scores and the Head and Neck QOL scores. Clinical measures were collected by chart abstraction. Kaplan-Meier plots and univariate and multivariate Cox proportional hazards models were used to determine the association between QOL scores and survival time. Results After controlling for age, time since diagnosis, marital status, education, tumor site and stage, comorbidities, and smoking, the SF-36 physical component score and three of the four Head and Neck QOL scales (pain, eating, and speech domains) were associated with survival. Controlling for the same variables, the SF-36 mental component score and the emotional domain of the Head and Neck QOL were not associated with survival. Conclusion QOL instruments may be valuable screening tools to identify patients who are at high risk for poor survival. Those with low QOL scores could be followed more closely, with the potential to identify recurrence earlier and perform salvage treatments, thereby possibly improving survival for this group of patients.
Influence of Clinical Communication on Patients' Decision Making on Participation in Clinical Trials
Authors: Albrecht Terrance L. , Eggly Susan S. , Gleason Marci E.J. , Harper Felicity W.K. , Foster Tanina S. , Peterson Amy M. , Orom Heather , Penner Louis A. , Ruckdeschel John C. 
Published: May 2008

PurposeTo investigate how communication among physicians, patients, and family/companions influences patients' decision making about participation in clinical trials.Patients and MethodsWe video recorded 235 outpatient interactions occurring among oncologists, patients, and family/companions (if present) at two comprehensive cancer centers. We combined interaction analysis of the real-time video-recorded observations (collected at Time 1) with patient self-reports (Time 2) to determine how communication about trial offers influenced accrual decisions.ResultsClinical trials were explicitly offered in 20% of the interactions. When offers were made and patients perceived they were offered a trial, 75% of patients assented. Observed messages (at Time 1) directly related to patients' self-reports regarding their decisions (2 weeks later), and how they felt about their decisions and their physicians. Specifically, messages that help build a sense of an alliance (among all parties, including the family/companions), provide support (tangible assistance and reassurance about managing adverse effects), and provide medical content in language that patients and family/companions understand are associated with the patient's decision and decision-making process.ConclusionIn two urban, National Cancer Institute–designated comprehensive cancer centers, a large percentage of patients are not offered trials. When offered a trial, most patients enroll. The quality and quantity of communication occurring among the oncologist, patient, and family/companion when trials are discussed matter in the patient's decision-making process. These findings can help increase physician awareness of the ways that messages and communication behaviors can be observed and evaluated to improve clinical practice and research.
Estrogen Receptor Expression and Efficacy of Docetaxel-Containing Adjuvant Chemotherapy in Patients With Node-Positive Breast Cancer: Results From a Pooled Analysis
Authors: Andre Fabrice , Broglio Kristine , Roche Henri , Martin Miguel , Mackey John R. , Penault-Llorca Frederique , Hortobagyi Gabriel N. , Pusztai Lajos 
Published: May 2008

Purpose Several adjuvant chemotherapy trials suggested that cytotoxic treatment is less effective in patients with estrogen receptor (ER) –positive breast cancers. The aim of the present study was to assess the efficacy of adjuvant docetaxel and anthracycline therapy according to ER expression in two randomized clinical trials. Patients and Methods Pooled data from two randomized trials, BCIRG001 and PACS01, were examined. Hazard ratios for recurrence and survival were estimated by Cox proportional hazards models and were adjusted for clinical variables. Interaction between docetaxel and ER expression was tested. Results ER status was available for 3,329 patients (95% of all randomly assigned patients), of whom 75% (n = 2,493) were ER positive. Docetaxel therapy was associated with a 30% reduction in the risk of death (hazard ratio [HR] = 0.70; 95% CI, 0.54 to 0.91) in ER-positive patients and a 31% reduction (HR = 0.69; 95% CI, 0.52 to 0.94) in ER-negative patients. Docetaxel therapy was associated with a 21% reduction in the risk of recurrence (HR = 0.79; 95% CI, 0.66 to 0.93) in ER-positive patients and a 31% reduction (HR = 0.69; 95% CI, 0.54 to 0.97) in ER-negative patients. The interaction between docetaxel therapy and ER status was not statistically significant for either overall survival (P = .87) or disease-free survival (P = .30). ER expression was also not predictive for docetaxel efficacy when it was analyzed as a semi-continuous variable based on percent of positive cells by immunohistochemistry (test for heterogeneity, P = .56 and .86 for overall survival and disease-free survival, respectively). Conclusion In the pooled analysis of these two trials, docetaxel did not have a statistically significantly different effect on the risk of recurrence or death in ER-positive and ER-negative patients.
Phase III Study of Valspodar (PSC 833) Combined With Paclitaxel and Carboplatin Compared With Paclitaxel and Carboplatin Alone in Patients With Stage IV or Suboptimally Debulked Stage III Epithelial Ovarian Cancer or Primary Peritoneal Cancer
Authors: Lhommé Catherine , Joly Florence , Walker Joan L. , Lissoni Andrea A. , Nicoletto Maria O. , Manikhas Gregory M. , Baekelandt Mark M.O. , Gordon Alan N. , Fracasso Paula M. , Mietlowski William L. , Jones Gary J. , Dugan Margaret H. 
Published: May 2008

Purpose To compare the safety and efficacy of carboplatin and paclitaxel administered with or without the multidrug resistance modulator valspodar (PSC 833) in untreated patients with advanced ovarian or primary peritoneal cancer. Patients and Methods Seven hundred sixty-two patients with stage IV or suboptimally debulked stage III ovarian or primary peritoneal cancer were randomly assigned to receive either valspodar 5 mg/kg every 6 hours for 12 doses, paclitaxel 80 mg/m2, and carboplatin area under the curve (AUC) 6 (PC-PSC; n = 381) or paclitaxel 175 mg/m2 and carboplatin AUC 6 (PC; n = 381). Time to disease progression (TTP) was the primary end point. Secondary end points were overall survival time (OS), response rate (RR), safety, and tolerability. Results With a median follow-up of 736 days (range, 1 to 2,280 days), the median TTP was 13.2 and 13.5 months in the PC-PSC and PC groups, respectively (P = .67); the median OS was 32 and 28.9 months, respectively (P = .94). The overall RR was higher in the PC group (41.5% v 33.6%; P = .02). Central and peripheral nervous system and GI toxicities were more common in the PC-PSC group. Ataxia occurred in 53.5% and 3.2% of PC-PSC–and PC-treated patients, respectively. Febrile neutropenia occurred more frequently in the PC-PSC group. More PC-PSC–treated patients discontinued therapy because of adverse events (AEs), experienced serious AEs, and required paclitaxel dose reductions. Conclusion The addition of valspodar to PC did not improve TTP or OS and was more toxic compared with PC in untreated patients with advanced ovarian or primary peritoneal cancer.
Phase I Trial of the Human Immunodeficiency Virus Protease Inhibitor Nelfinavir and Chemoradiation for Locally Advanced Pancreatic Cancer
Authors: Brunner Thomas B. , Geiger Matthias , Grabenbauer Gerhard G. , Lang-Welzenbach Marga , Mantoni Tine S. , Cavallaro Alexander , Sauer Rolf , Hohenberger Werner , McKenna W. Gillies 
Published: May 2008

Purpose Preclinically, HIV protease inhibitors radiosensitize tumors with activated PI3-kinase/Akt pathway. We determined the toxicity of nelfinavir chemoradiotherapy in borderline resectable and unresectable pancreatic cancer. Patients and Methods Oral nelfinavir (2 × 1,250 mg) was started 3 days before and continued throughout chemoradiotherapy to 50.4 Gy (boost, 59.4 Gy) in 12 patients. Two gemcitabine dose levels (DL) were tested (200 mg/m2 and 300 mg/m2 on days 1, 8, 22, and 29). Cisplatin was administered on the same days at 30 mg/m2. Phospho-Akt downregulation by nelfinavir was monitored by immunoblotting in patient leukocytes. Restaging positron emission tomography (PET)/computed tomography (CT) and CA19-9 levels served to assess response, and responding tumors were resected. Results At each DL, five of six patients completed chemoradiotherapy, and two of 12 patients had incomplete chemoradiotherapy because of clinical depression (DL1) and peritoneal metastasis (DL2). Grade 4 toxicities were a transaminase elevation (DL2) as a result of biliary stent occlusion and acute cholecystitis as a result of peritoneal metastasis (DL2). Stent occlusions led to dose-limiting toxicities of grade 3 liver enzyme and bilirubin elevations (two patients at DL1, one patient at DL2). Grade 3 nausea and vomiting occurred in a DL2 patient, and weight loss occurred in a DL1 patient who refused supportive feeding. Secondary complete resection was possible in six of 10 patients with complete chemoradiotherapy, including one tumor with pathologic sterilization. Partial CT responses were observed in five of 10 patients who completed chemoradiotherapy. Of nine patients assessable by PET,responses were complete in five patients and partial patients, and stable disease was observed in two patients. Conclusion The combination of nelfinavir and chemoradiotherapy showed acceptable toxicity and promising activity in patients with pancreatic cancer.