bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract S4-1: FinXX Final 5-Year Analysis: Results of the Randomised, Open-Label, Phase III Trial in Medium-to-High Risk Early Breast Cancer
Authors: Joensuu H , Kellokumpu-Lehtinen P-L , Huovinen R , Jukkola-Vuorinen A , Tanner M , Kokko R , Ahlgren J , Auvinen P , Bono P , Lindman H 
Published: April 2011

Abstract
Background: The randomised, phase III FinXX trial (NCT00114816) investigated whether the integration of capecitabine (X) into a sequential docetaxel (T)→cyclophosphamide + epirubicin + 5-FU (CEF) adjuvant regimen might improve clinical outcome for patients with medium-to-high risk early breast cancer. The planned interim analysis after a median follow-up of 3 years found a significant recurrence-free survival (RFS) benefit with the X-containing regimen versus control (3-year RFS rate: 93% XTP→ukkalaCEX vs 89% T→CEF; hazard ratio 0.66 [95% CI: 0.47-0.94]; p=0.020) [Lancet Oncol 2009;10:1145-51]. Here we present final 5-year RFS data, the primary endpoint of the study.
Methods: Eligible patients were aged 18-65 years, had a WHO performance status of 0 or 1 and histologically confirmed invasive breast cancer at medium-to-high risk of recurrence, defined as regional node-positive disease or node-negative disease with primary tumour diameter greater than 20mm and negative progesterone receptor assay. Previous neoadjuvant chemotherapy was not permitted. Patients were randomised in a 1:1 ratio to receive 3 cycles of T→3 cycles of CEF (T→CEF; T 80mg/m2 d1, q3w→C 600mg/m2 d1, E 75mg/m2 d1, F 600mg/m2 d1, q3w) or 3 cycles of XT→3 cycles of CEX (XT→CEX; X 900mg/m2 bid d1-15 + T 60mg/m2 d1, q3w→C 600mg/m2 d1, E 75mg/m2 d1, X 900mg/m2 bid d1-15, q3w). The primary endpoint was RFS, defined as the time from randomisation to the first time the patient is recorded as having disease recurrence or the date of death if the patient dies due to causes other than disease recurrence; secondary endpoints were overall survival and safety. Results: Between January 2004 and May 2007, 1,500 women from Finland and Sweden were randomised to T→CEF (n=747) or XT→CEX (n=753). Final analysis of the primary endpoint will be presented after a median follow-up of 5 years and approximately 200 events. Data are expected in October 2010.
Conclusions: The FinXX trial was the first to report the efficacy and safety of X in combination with anthracycline/taxane-containing therapy in the adjuvant treatment of early breast cancer. Final efficacy data are expected in October 2010.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S4-1.
Abstract S5-4: Synthetic-Lethality of Triple-Negative Breast Cancers Via the MYC Oncogene Pathway
Authors: Goga A , Horiuchi D , Kusdra L , Chandriani S , Lenburg ME , Gonzalez-Angulo AM , Huskey NE , Creasman KJ , Davis SE , Mills GB , Esserman LJ. 
Published: April 2011

Abstract
Background: Breast cancer lacking the estrogen, progesterone and ERBB2 receptors, (“triple-negative”) encompasses an aggressive sub-type that is associated with a higher incidence of early tumor recurrence and poor patient outcome, particularly after distant relapse. The lack of validated targets means that only conventional cytotoxic chemotherapy offers significant benefits, albeit with associated toxicities and lack of specificity. Among many potential therapeutic targets in triple-negative breast cancer, MYC may be important as its function is elevated in many breast cancers with aggressive phenotypes.
Methods: In this study we investigate the association between MYC abundance in primary breast tumors using two large clinical cohorts and examined MYC mRNA and protein abundance as well as the expression of a MYC gene signature. We next examined the association between the MYC gene signature and patient response to neoadjuvant chemotherapy as well as disease-free survival in the ISPY TRIAL. Furthermore, we examined whether high MYC expression in triple-negative tumors might provide a new therapeutic approach in this tumor sub-type. We tested a synthetic-lethal strategy to kill triple-negative breast cells with abundant MYC expression by inhibiting cyclin-dependent kinases (CDKs). Results: We find that human triple-negative breast cell lines have significantly elevated MYC mRNA and protein expression. These results were validated using primary patient tumor samples from the neoadjuvant ISPY TRIAL (N= 138 patients) as well as a separate cohort of primary tumor samples for which quantitative protein expression was determined (N= 208 patients). In the ISPY TRIAL an increased expression of the MYC gene signature was associated with worse outcome in patients with substantial residual tumor burden after neoadjuvant chemotherapy (RCB Class II and III). We sought to exploit this increased MYC activity in triple-negative tumors using a synthetic-lethal approach dependent on cyclin-dependent kinase (CDK) inhibition. We found that triple-negative breast tumor cells undergo cell death in a MYC-dependent manner following treatment with several CDK inhibitors, including SCH72796 that is in Phase II clinical trials. We find that CDK inhibition effectively induces tumor regression in human tumor xenografts. CDK inhibition in triple-negative breast cells up-regulates the pro-apoptotic BCL2 family member BIM. Our findings support the exploration of CDK inhibitors as treatment for triple-negative breast cancers.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S5-4.
Abstract S6-10: Identification of a Novel Tumor Suppressor Network Reveals a Role for Proto-Oncogenic Receptor Tyrosine Kinases in Triple-Negative Breast Cancer
Authors: Sun T , Meerbrey KL , Kessler J , Botero M , Migliaccio I , Nguyen DX , Pavlova NN , Bernardi RJ , Schmitt E , Hilsenbeck SG , Creighton CJ , Shaw CA , Gibbs R , Wheeler D , Osborne CK , Schiff R , Elledge SJ , Westbrook TF. 
Published: April 2011

Abstract
Breast cancer is a collection of diseases with distinct clinical behaviors and underlying genetic causes. Triple-negative breast cancer (TNBC) is a common subtype of breast cancer that confers a particularly poor prognosis and is refractory to current targeted therapies. Unfortunately, the molecular determinants driving this aggressive malignancy are poorly understood. Using an unbiased genetic screen, we have identified a novel tumor suppressor network that governs proliferation and transformation of TNBCs in vitro and in vivo. We define SECT21 as a core component in this network and a commonly inactivated tumor suppressor in TNBC. SECT21 is a potent suppressor of human mammary epithelial cell proliferation and transformation. SECT21 function is frequently compromised in human TNBCs by inactivating mutations, deletion, or loss of protein expression. Mechanistically, SECT21 is a tyrosine phosphatase that suppresses cellular transformation by interacting with and inhibiting several oncogenic receptor tyrosine kinases including HER2, EGFR, and PDGFR. Notably, the tumorigenic and metastatic potential of SECT21-deficient TNBCs is severely impaired by restoring SECT21 function or by inhibiting kinase targets of SECT21, suggesting that TNBCs are dependent on the proto-oncogenic tyrosine kinases constrained by SECT21. Collectively, these data identify SECT21 as a commonly inactivated tumor suppressor and provide a rationale for combinatorially targeting tyrosine kinases in TNBC and other cancers based on their profile of tyrosine phosphatase activity.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S6-10.
Abstract S6-4: Association between Prescription Co-Payment Amount and Compliance with Adjuvant Aromatase Inhibitor Therapy in Women with Early Stage Breast Cancer
Authors: Hershman DL , Neugut AI , Subar M , Wilde ET , Stratton S , Brouse CH , Hillyer G , Grann V. 
Published: April 2011

Abstract
Background: Non-adherence to adjuvant hormonal therapy among women with breast cancer is common, but little is known about how financial factors influence it. We investigated the relationship between prescription co-payment amount and compliance with adjuvant aromatase inhibitors (AI) therapy.
Patients and Methods: Using de-identified, integrated pharmacy and medical claim database at Medco Health Solutions, Inc. women &gt;50 years old on AIs for early breast cancer with at least 2 mail order prescription refills between 1/1/07 and 12/31/08 were identified. All data were pooled prior to the analysis. Variables that were evaluated included medical and demographic information, household income, number of other prescriptions, diagnostic codes, prescription refill dates, provider type and co-payment amounts. Age was classified as &lt;63 or ≥63 to distinguish patients ever covered by Medicare. Copayment amount was categorized as &lt;$30, between $30 and $89.99, and ≥$90. Non-persistence was defined as prescription supply gap of 45 days with no subsequent refill. Non-adherence was defined as a medication possession ratio ≥80% of eligible days. Logistic regressions and Cox proportional hazards modeling were used. Results: Of 8110 women age 50-62 years (mean=59.1), 1721(21.2%) were non-persistent and of those who continued, 863(10.3%) were non-adherent over the 2 year period. Among 14,050 women ≥63 years (mean=74.9), 3476(24.7%) were non-persistent and of those who continued, 1248(8.9%) were non-adherent. Ninety day co-payments ranged from $0 to $893.49. In a multivariate analysis, non-persistence (ever/never) in both age groups was associated with older age, having a primary care physician write the prescription, and higher number of co-prescriptions. Similar results were seen with non-adherence. Compared to a copayment of &lt;$30, a 90 day copayment of $30-$89.99 was associated with time to non-persistence in women ≥63 (HR 1.34, 95%CI 1.24-1.46) but not among women &lt;63, while a copayment ≥$90 was associated with time to non-persistence both in women &lt;63 (HR 1.26, 95%CI 1.09–1.38) and women ≥63 (HR 1.33, 95%CI 1.22–1.46).
Conclusions: We found that a higher prescription co-payment was associated with both early discontinuation and non-adherence to AIs. This relationship was stronger for older women. Because hormone therapy non-compliance is associated with worse survival outcomes, future public policy efforts should be directed towards reducing financial constraints as a means of increasing the use of these life-saving medications.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S6-4.
Abstract S6-8: Hedgehog Ligand Overexpression Predicts Poor Outcome in Breast Cancer and Is a Potential Therapeutic Target for Metastatic Disease
Authors: O'Toole SA , Machalek D , Shearer R , Millar EKA , Nair R , Martelotto L , McLeod D , Cooper C , Ru Qiu M , Sutherland RL , Watkins DN , Swarbrick A. 
Published: April 2011

Abstract
Background: The Hh signalling pathway plays an important role in a number of malignancies, and accumulating data suggest it contributes significantly to the development and progression of breast cancer. However, there is scant data regarding the clinical significance of its dysregulation in breast cancer and its functional effects in breast cancer models.
Methods: We investigated the clinical significance of the expression of Hh pathway components using immunohistochemistry in a well-characterised cohort of 279 patients with invasive ductal carcinoma (IDC) to determine its prognostic significance. A murine mammary cancer allograft model based on the M6 cell line, derived from the C3/SV40T transgenic mouse was used to determine the effects of Shh overexpression on tumour growth in vitro and in vivo. Finally, the therapeutic potential of Hh blockade using the monoclonal antibody 5E1 was also explored in two mouse mammary carcinoma models; the M6 allograft model and the highly metastatic 4T1 cell line in immunocompetent Balb/C mice.
Results: High Hh ligand expression was observed in 34% of IDC and was associated with increased risk of breast cancer recurrence (HR 1.95, p=0.0004) and breast cancer specific death (HR 2.3, p=0.0002). High Hh expression was also associated with the basal-like subtype (p=0.004). Overexpression of Hh ligand in M6 cells transplanted to fat pads of immunodeficient mice resulted in a 4 fold increase in tumor volume (p= 0.006) and was associated with upregulation of the canonical Hh target genes Gli1 and HHIP. However, Shh promoted peritumoral lymphatic invasion in 4/5 mice compared to only 1/5 in the vector control group and was associated with a significantly shorter time to the development of metastatic disease (p=0.0004). M6 cells overexpressing Hh ligand showed no change in proliferation, self renewal or migration in vitro, suggesting a requirement for stromal interaction in Hh-dependent tumor promotion. Finally, we found that the enhanced tumor growth conferred by Hh ligand overexpression could be blocked by administration of a neutralizing antibody to Hh ligand. Furthermore, using a metastatic mammary carcinoma isograft model (4T1) that endogenously expresses Hh ligand, we demonstrate that Hh blockade resulted in smaller lung metastatic deposits (p=0.045).
Conclusions: We found that high Hh ligand is associated with a poor prognosis in IDC. Overexpression of Hh ligand promotes murine mammary tumor growth, which requires stromal interaction, as well as lymphatic vessel invasion. Finally, we demonstrate that blockade of the Hh ligand is a potential therapy in metastatic breast carcinoma.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S6-8.
FGFR3 Is Overexpressed Waldenström Macroglobulinemia and Its Inhibition by Dovitinib Induces Apoptosis and Overcomes Stroma-Induced Proliferation
Authors: Azab Abdel Kareem , Azab Feda , Quang Phong , Maiso Patricia , Sacco Antonio , Ngo Hai T. , Liu Yang , Zhang Yong , Morgan Brittany L. , Roccaro Aldo M. , Ghobrial Irene M. 
Published: April 2011

Abstract
Purpose: There is no standard of therapy for the treatment of Waldenström macroglobulinemia (WM), therefore there is a need for the development of new agents. Fibroblast growth factor receptor 3 (FGFR3) was shown to play a major role in several types in cancer. Dovitinib, an inhibitor of FGFR3, was effective in hematologic malignancies. In this study, we tested FGFR3 as a therapeutic target in WM and tested the effect of dovitinib on cell proliferation and apoptosis of WM cells in the context of BM microenvironment.
Methods: The expression of FGFR3 in WM cells was tested using immunofluorescence and flow cytometry. Cell signaling in response to stimulation with FGF3 and stromal cells, and its inhibition by dovitinib was performed using immunoblotting. Cell survival and cell proliferation were assessed by MTT and BrdU assays. Apoptosis was measured by detection of APO-2.7 and cleavage of caspase-3 using flow cytometry. Cell cycle was performed by PI staining of cells and flow cytometry. The combinatory effect of dovitinib with other drugs was analyzed using Calcusyn software. The effect of dovitinib was tested in vivo.
Results: FGFR3 was overexpressed in WM cells and its activation induced cell proliferation. Inhibition of FGFR3 with dovitinib decreased cell survival, increased apoptosis, and induced cell cycle arrest. Inhibition of FGFR3 by dovitinib reduced the interaction of WM to bone marrow components, and reversed its proliferative effect. Dovitinib had an additive effect with other drugs. Moreover, dovitinib reduced WM tumor progression in vivo.
Conclusion: We report that FGFR3 is a novel therapeutic target in WM, and suggest dovitinib for future clinical trial the treatment of patients with WM. Clin Cancer Res; 17(13); 4389–99. ©2011 AACR.
Validity of Estimated Glomerular Filtration Rates for Assessment of Baseline and Serial Renal Function in Patients With Atherosclerotic Renal Artery Stenosis
Authors: Madder Ryan D. , Hickman Leaden , Crimmins Geoffrey M. , Puri Mohammad , Marinescu Victor , McCullough Peter A. , Safian Robert D. 
Published: April 2011

Background—
Despite routine use of estimated glomerular filtration rates (GFRs) as major renal end points in clinical trials of renal revascularization, serial GFR estimates have never been validated in patients with renal artery stenosis (RAS). The purpose of this study was to evaluate the validity of GFR estimates in patients with atherosclerotic RAS.

Methods and Results—

Serum creatinine (SCr) and
125
I-iothalamate GFR (I-GFR) were measured in patients with RAS. GFR estimates were calculated from Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockroft-Gault (CG) formulas. Using I-GFR as the reference standard, the sensitivity, specificity, and receiver operating characteristic area under the curve (AUC) were determined for MDRD, CKD-EPI, CG, and reciprocal SCr for identifying I-GFR <60 mL/min per 1.73 m
2
and a 20% change in I-GFR over time. Between 1998 and 2007, 541 I-GFR measurements were performed in 254 consecutive patients with RAS. MDRD, CKD-EPI, and CG GFR estimates demonstrated good sensitivity (86% to 95%), modest specificity (67% to 71%), and good reliability (AUC, 0.86 to 0.94) for identifying I-GFR <60 mL/min per 1.73 m
2
. GFR estimates had good specificity (87% to 95%), poor sensitivity (0% to 45%), and poor reliability (AUC, 0.61 to 0.65) for detecting 20% changes in I-GFR over follow-up.

Conclusions—

In patients with RAS, GFR estimates demonstrate good sensitivity and modest specificity for identifying I-GFR <60 mL/min per 1.73 m
2
but poor sensitivity and reliability for detecting 20% changes in I-GFR. GFR estimates should not be used in clinical trials as major end points to assess serial GFR after renal revascularization.
Relationships between Snow and the Wintertime Minneapolis Urban Heat Island
Authors: Malevich Steven B. , Klink Katherine 
Published: April 2011

AbstractUrban heat islands (UHIs) are one of the best-recorded incidences of anthropogenic climate change. Studies from across the globe have examined this phenomenon, but relatively few have focused on cold-winter cities and the effects of snow cover and snowfall. This study uses hourly temperature measurements from 1 December 2008 through 28 February 2009 at 22 urban sites in Minneapolis, Minnesota, to investigate the effect of snow cover and snowfall on the UHI. Snow effects on temperature are estimated for calm conditions using a linear mixed-effect (LME) model. For the winter of 2008/09, the average wintertime UHI was approximately 1.0°C, with a peak near midday rather than at night. The LME model results suggest that a snow cover of 5 cm or more increased the magnitude of the UHI by about 1.0°C during the day and by about 0.5°C at night. The model also indicates that the presence of moderate snowfall decreased the magnitude of the UHI by up to 2.0°C, although this result is based on a comparatively small number of events. The high albedo of snow is posited to contribute to the enhanced UHI during the day, and snow’s insulating properties are likely contributors to the characteristics of the nighttime UHI.
Tobacco Use among Rural African American Young Adult Males
Authors: Carroll William R. , Foushee Herman R. , Hardy Claudia M. , Floyd Tammi , Sinclair Catherine F. , Scarinci Isabel 
Published: April 2011

ObjectiveTobacco‐related disease is a primary source of mortality for African American men. Recent studies suggest that alternative tobacco products may have supplanted cigarettes as the most common products used by young African Americans. Effective cessation strategies require community‐specific prevalence data. This project measures the prevalence of 9 tobacco products among young African American men in rural Alabama.Study DesignPrinciples of community‐based participatory research were used to design a verbally administered tobacco product survey to measure the prevalence and behavioral factors influencing use.SettingBlack Belt counties of rural Alabama.Subjects and MethodsAfrican American men aged 19 to 30 years were recruited from the target counties. Participants were stratified by income and education level. Prevalence rates for 9 products were determined, and logistic regression analysis was performed.ResultsA total of 415 participants completed surveys. Cigarettes were the most common product ever (54%) and currently (39.9%) used. Participants who attended school for more than 12 years or attended religious services were less likely to use cigarettes. Marijuana and blunts were used next most commonly. Only 35 respondents (8.9%) currently used mini‐cigars. Other products, bidis/kreteks, smokeless tobacco, and pipes were used uncommonly in this sample.ConclusionsCigarettes remain the dominant tobacco product used by young African American men in rural Alabama. Cigarette prevalence far exceeds that measured statewide for African American men of the same age. Alternative products were not commonly used in this study population. Effective community‐based intervention must target cigarette initiation and cessation in this vulnerable population.
Improved Airway Visualization during Direct Laryngoscopy Using Self‐retaining Laryngeal Retractors
Authors: Longstreet Beck , Bhama Prabhat K. , Inglis Andrew F. , Saltzman Babette , Perkins Jonathan A. 
Published: April 2011

ObjectiveTo measure the degree to which the Lindholm laryngeal distending forceps improve visualization during direct laryngoscopy in selected pediatric patients.Study DesignCase series with chart review.SettingPediatric hospital.Subjects and MethodsSubjects included children undergoing direct laryngoscopy using the Lindholm laryngeal distending forceps. Intraoperative endoscopic photos with and without false cord retraction via the Lindholm laryngeal distending forceps were obtained from the Seattle Children’s Hospital airway endoscopy photo library. Analysis was performed using imaging software. Comparisons of visible vocal cord and glottic opening areas as well as anterior commissure angles with and without the Lindholm laryngeal distending forceps were performed with a paired and unpaired Student t test.ResultsThe use of the Lindholm laryngeal distending forceps increased the glottic opening by a mean of 359% (95% confidence interval [CI], 255%‐463%) and increased visualized true vocal cord area by 337% (197%‐477%). Angle at the anterior commissure increased from a mean of 24.9° to a mean of 71.5°, resulting in a net mean angle increase of 46.6° (95% CI, 40.2°‐52.9°). All measured changes were statistically significant with P values <.01.ConclusionsWhen placed at the level of the false vocal folds, Lindholm laryngeal distending forceps will, at least in certain cases, greatly increase the visible area of the superior surface of the vocal folds, the anterior commissure, and, by increasing the glottic opening, the subglottic region. This improved visualization may enhance the surgeon’s ability to diagnose and treat pathologies in these anatomic regions during direct laryngoscopy.