bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ki67 Expression and Docetaxel Efficacy in Patients With Estrogen Receptor–Positive Breast Cancer
Authors: Penault-Llorca Frédérique , André Fabrice , Sagan Christine , Lacroix-Triki Magali , Denoux Yves , Verriele Veronique , Jacquemier Jocelyne , Baranzelli Marie Christine , Bibeau Frederic , Antoine Martine , Lagarde Nicole , Martin Anne-Laure , Asselain Bernard , Roché Henri 
Published: April 2009

Purpose The indications of adjuvant chemotherapy for patients with estrogen receptor (ER) –positive breast cancer are controversial. We analyzed the predictive value of Ki67, HER2, and progesterone receptor (PR) expression for the efficacy of docetaxel in patients with ER-positive, node-positive breast cancer. Patients and Methods Expression of Ki67, HER2, and PR was measured by immunohistochemistry in tumor samples from 798 patients with ER-positive breast cancer who participated in PACS01, a randomized trial that evaluated the efficacy of docetaxel. Risk reduction was evaluated using a Cox model adjusted for age, tumor size, nodal involvement, treatment arm, and biomarkers. The predictive value of biomarkers was assessed by an interaction test. Disease-free survival (DFS) was the primary end point. Results Ki67, HER2, and PR were expressed in 21%, 9%, and 62% of samples, respectively. Hazard ratios for relapse associated with docetaxel were 0.51 (95% CI, 0.26 to 1.01) in ER-positive/Ki67-positive tumors and 1.03 (95% CI, 0.69 to 1.55) in ER-positive/Ki67-negative tumors (ratio for interaction: 0.53; 95% CI, 0.24 to 1.16; P = .11). Five-year DFS rates were 81% (95% CI, 76% to 86%) and 84% (95% CI, 75% to 93%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with docetaxel and 81% (95% CI, 76% to 86%) and 62% (95% CI, 52% to 72%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with fluorouracil, epirubicin, and cisplatin. No trend for interaction was observed between docetaxel and HER2 (ratio for interaction: 0.83; 95% CI, 0.35 to 1.94; P = .66), nor between docetaxel and PR (ratio for interaction: 0.89; 95% CI, 0.47 to 1.66; P = .71). Conclusion Ki67 expression identifies a subset of patients with ER-positive breast cancer who could be sensitive to docetaxel treatment in the adjuvant setting.
Endocrine Effects of Adjuvant Letrozole Compared With Tamoxifen in Hormone-Responsive Postmenopausal Patients With Early Breast Cancer: The HOBOE Trial
Authors: Rossi Emanuela , Morabito Alessandro , Di Rella Francesca , Esposito Giuseppe , Gravina Adriano , Labonia Vincenzo , Landi Gabriella , Nuzzo Francesco , Pacilio Carmen , De Maio Ermelinda , Di Maio Massimo , Piccirillo Maria Carmela , De Feo Gianfranco , D'Aiuto Giuseppe , Botti Gerardo , Chiodini Paolo , Gallo Ciro , Perrone Francesco , de Matteis Andrea 
Published: April 2009

Purpose We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. Patients and Methods Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. Conclusion Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.
Phase II Randomized Study of Neoadjuvant Everolimus Plus Letrozole Compared With Placebo Plus Letrozole in Patients With Estrogen Receptor–Positive Breast Cancer
Authors: Baselga José , Semiglazov Vladimir , van Dam Peter , Manikhas Alexey , Bellet Meritxell , Mayordomo José , Campone Mario , Kubista Ernst , Greil Richard , Bianchi Giulia , Steinseifer Jutta , Molloy Betty , Tokaji Erika , Gardner Humphrey , Phillips Penny , Stumm Michael , Lane Heidi A. , Dixon J. Michael , Jonat Walter , Rugo Hope S. 
Published: April 2009

Purpose Cross-talk between the estrogen receptor (ER) and the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathways is a mechanism of resistance to endocrine therapy, and blockade of both pathways enhances antitumor activity in preclinical models. This study explored whether sensitivity to letrozole was enhanced with the oral mTOR inhibitor, everolimus (RAD001). Patients and Methods Two hundred seventy postmenopausal women with operable ER-positive breast cancer were randomly assigned to receive 4 months of neoadjuvant treatment with letrozole (2.5 mg/day) and either everolimus (10 mg/day) or placebo. The primary end point was clinical response by palpation. Mandatory biopsies were obtained at baseline and after 2 weeks of treatment (ie, day 15). Samples were assessed for PI3K mutation status (PIK3CA) and for pharmacodynamic changes of Ki67, phospho-S6, cyclin D1, and progesterone receptor (PgR) by immunohistochemistry. Results Response rate by clinical palpation in the everolimus arm was higher than that with letrozole alone (ie, placebo; 68.1% v 59.1%), which was statistically significant at the preplanned, one-sided, α = 0.1 level (P = .062). Marked reductions in progesterone receptor and cyclin D1 expression occurred in both treatment arms, and dramatic downregulation of phospho-S6 occurred only in the everolimus arm. An antiproliferative response, as defined by a reduction in Ki67 expression to natural logarithm of percentage positive Ki67 of less than 1 at day 15, occurred in 52 (57%) of 91 patients in the everolimus arm and in 25 (30%) of 82 patients in the placebo arm (P < .01). The safety profile was consistent with historical results of everolimus monotherapy; grades 3 to 4 adverse events occurred in 22.6% of patients who received everolimus and in 3.8% of patients who received placebo. Conclusion Everolimus significantly increased letrozole efficacy in neoadjuvant therapy of patients with ER-positive breast cancer.
Progression-Free Survival as a Predictor of Overall Survival in Men With Castrate-Resistant Prostate Cancer
Authors: Halabi Susan , Vogelzang Nicholas J. , Ou San-San , Owzar Kouros , Archer Laura , Small Eric J. 
Published: April 2009

PurposeTo explore whether progression-free survival (PFS) or biochemical PFS can be used as a predictor of overall survival (OS) and to investigate the dependence between PFS and OS in men with castrate-resistant prostate cancer.Patients and MethodsData from nine Cancer and Leukemia Group B trials that enrolled 1,296 men from 1991 to 2004 were pooled. Men were eligible if they had prostate cancer that had progressed during androgen deprivation therapy and did not receive prior treatment with chemotherapy, immunotherapy, or other nonhormonal therapy. Landmark analyses of PFS at 3 and 6 months from randomization/registration were performed to minimize lead time bias. The proportional hazards model was used to assess the significance effect of PFS rate at 3 and at 6 months in predicting OS. In addition, biochemical progression using the definitions of Prostate-Specific Antigen Working Group (PSAW) Criteria PSAWG1 and PSAWG2 were analyzed as time-dependent covariates in predicting OS.ResultsThe median survival time among men who experienced progression at 3 months was 9.2 months (95% CI, 8.0 to 10.0 months) compared with 17.8 months in men who did not experience progression at 3 months (95% CI, 16.2 to 20.4 months; P < .0001). Compared with men who did not progress at 3 and at 6 months, the adjusted hazard ratios for death were 2.0 (95% CI, 1.7 to 2.4; P < .001) and 1.9 (95% CI, 1.6 to 2.4; P < .001) for men who experienced progression at 3 and 6 months, respectively. In addition, biochemical progression at 3 months predicted OS. The association between PFS and OS was 0.30 (95% confidence limits = 0.26, 0.32).ConclusionPFS at 3 and 6 months and biochemical progression at 3 months predict OS. These observations require prospective validation.
Oxidative Stress, Obesity, and Breast Cancer Risk: Results From the Shanghai Women's Health Study
Authors: Dai Qi , Gao Yu-Tang , Shu Xiao-Ou , Yang Gong , Milne Ginger , Cai Qiuyin , Wen Wanqing , Rothman Nathaniel , Cai Hui , Li Honglan , Xiang Yongbing , Chow Wong-Ho , Zheng Wei 
Published: April 2009

Purpose Increased reactive oxygen species may exhaust the antioxidant capability of human defense systems, leading to oxidative stress and cancer development. Urinary F2-isoprostanes, secondary end products of lipid peroxidation, are more accurate markers of oxidative stress than other available biomarkers. No prospective study has investigated whether levels of 15-F2t-isoprostane (15-F2t-IsoP) and its metabolite 2,3-dinor-5,6-dihydro-15-F2t-IsoP (15-F2t-IsoPM) are related to breast cancer risk. Patients and Methods We conducted a nested case-control study within the Shanghai Women's Health Study, a population-based cohort study of 74,942 Chinese women between 40 and 70 years of age. Prediagnostic urinary 15-F2t-IsoP and 15-F2t-IsoPM were measured by gas chromatography mass spectrometry for 436 breast cancer cases and 852 individually matched controls. Results Urinary excretion of isoprostanes was not significantly different between cases and controls. However, among overweight women, levels of isoprostanes were positively associated with breast cancer risk, which became stronger with increasing body mass index (BMI). Among women with a BMI ≥ 29, the odds ratio (OR) increased to 10.27 (95% CI, 2.41 to 43.80) for the highest compared with the lowest tertile of 15-F2t-IsoPM (P for trend = .003; P for interaction = .0004). In contrast, 15-F2t-IsoP and 15-F2t-IsoPM were inversely associated with breast cancer risk among nonoverweight women. Among women with a BMI ≤ 23, breast cancer risk was reduced with increasing 15-F2t-IsoP levels in a dose-response manner (P for trend = .006), with an OR of 0.46 (95% CI, 0.26 to 0.80) for the highest tertile versus the lowest (P for interaction = .006). Conclusion Our results suggest that the role of oxidative stress in breast cancer development may depend on adiposity.
Prostate-Specific Antigen Progression Predicts Overall Survival in Patients With Metastatic Prostate Cancer: Data from Southwest Oncology Group Trials 9346 (Intergroup Study 0162) and 9916
Authors: Hussain Maha , Goldman Bryan , Tangen Cathy , Higano Celestia S. , Petrylak Daniel P. , Wilding George , Akdas Atif M. , Small Eric J. , Donnelly Bryan J. , Sundram Subramanian Kanaga , Burch Patrick A. , DiPaola Robert S. , Crawford E. David 
Published: April 2009

Purpose Prostate-specific antigen progression (PSA-P) is an indicator of progression in hormone-sensitive (HS) and castration-resistant (CR) prostate cancer (PC). We evaluated different definitions of PSA-P as predictors of overall survival (OS). Patients and Methods A total of 1,078 patients with HSPC who were on hormones (Southwest Oncology Group [SWOG] trial 9346 [S9346]) and 597 patients with CRPC who were treated with chemotherapy (SWOG trial 9916 [S9916]) were eligible for this analysis. PSA-P definitions tested included the following: PSA Working Group, Prostate Cancer Working Group (PCWG 2008), and other definitions. A time-varying approach analyzed associations between PSA-P at any time and OS. A landmark analysis examined the relationship between PSA-P status at 7 months for S9346, or 3 months for S9916, and subsequent OS. Results In the time-varying analysis, both working groups definitions were strongly associated with OS (P < .001) in both study settings. In patients enrolled onto S9346, both definitions predicted a 2.4-fold increased risk of death (ROD) and a greater than four-fold increased ROD if PSA-P occurred in the first 7 months. In S9916, they predicted a 40% increase in ROD and a two-fold increase in ROD if PSA-P occurred at 3 months. In landmark analyses of patients on S9346 by using the PCWG 2008 definition of PSA-P, median subsequent OS was 10 months versus 44 months in patients who did or did not have PSA-P by 7 months, respectively; in S9916, data were 11 months versus 18 months for patients who did or did not have PSA-P by 3 months, respectively. Conclusion PSA-P, defined as an increase of ≥ 25% greater than the nadir and an absolute increase of at least 2 or 5 ng/mL, predicts OS in HSPC and CRPC and may be a suitable end point for phase II studies in these settings.
Phase III Noninferiority Trial Comparing Irinotecan With Oxaliplatin, Fluorouracil, and Leucovorin in Patients With Advanced Colorectal Carcinoma Previously Treated With Fluorouracil: N9841
Authors: Kim George P. , Sargent Daniel J. , Mahoney Michelle R. , Rowland Kendrith M. , Philip Philip A. , Mitchell Edith , Mathews Abraham P. , Fitch Tom R. , Goldberg Richard M. , Alberts Steven R. , Pitot Henry C. 
Published: April 2009

Purpose The primary goal of this multicenter phase III trial was to determine whether overall survival (OS) of fluorouracil (FU) -refractory patients was noninferior when treated with second-line infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4; arm B) versus irinotecan (arm A). Cross-over to the other treatment on disease progression was mandated. Patients and Methods Patients who experienced treatment failure with one prior FU-based therapy and had not received prior irinotecan or oxaliplatin, either for metastatic disease or within 6 months of adjuvant FU therapy, were randomly assigned to arm A (irinotecan 350 or 300 mg/m2 every 3 weeks) or arm B (FOLFOX4). Results A total of 491 patients were randomly assigned (arm A, n = 245; arm B, n = 246); 288 (59%) had experienced treatment failure with FU for metastatic colorectal cancer. Two hundred twenty-seven patients (46%) received protocol-mandated third-line therapy (arm A, 43%; arm B, 57%). Median survival was 13.8 months (95% CI, 12.2 to 15.0 months) for initial treatment with FOLFOX4 and 14.3 months (95% CI, 12.0 to 15.9 months) for irinotecan (P = .38; hazard ratio = 0.92; 95% CI, 0.8 to 1.1). Response rates (RR; 28% v 15.5%; P = .0009) and time to progression (TTP; 6.2 v 4.4 months; P = .0009) were significantly superior with FOLFOX4. In the nonrandom subset of patients who crossed over, RR and TTP improvements with FOLFOX4 continued into third-line treatment. Irinotecan therapy was associated with more grade 3 nausea, vomiting, diarrhea, and febrile neutropenia; FOLFOX4 was associated with more neutropenia and paresthesias. Conclusion In patients who experienced treatment failure with front-line FU therapy, OS does not significantly differ whether second-line therapy begins with irinotecan or FOLFOX4. FOLFOX4 produces higher RR and longer TTP. Both arms had notable OS in patients who experienced treatment failure with first-line FU therapy.
Primary Care Physicians' Views of Routine Follow-Up Care of Cancer Survivors
Authors: Del Giudice M. Elisabeth , Grunfeld Eva , Harvey Bart J. , Piliotis Eugenia , Verma Sunil 
Published: April 2009

Purpose Routine follow-up of adult cancer survivors is an important clinical and health service issue. Because of a lack of evidence supporting advantages of long-term follow-up care in oncology clinics, there is increasing interest for the locus of this care to be provided by primary care physicians (PCPs). However, current Canadian PCP views on this issue have been largely unknown. Methods A mail survey of a random sample of PCPs across Canada, stratified by region and proximity to urban centers, was conducted. Views on routine follow-up of adult cancer survivors and modalities to facilitate PCPs in providing this care were determined. Results A total of 330 PCPs responded (adjusted response rate, 51.7%). After completion of active treatment, PCPs were willing to assume exclusive responsibility for routine follow-up care after 2.4 ± 2.3 years had elapsed for prostate cancer, 2.6 ± 2.6 years for colorectal cancer, 2.8 ± 2.5 years for breast cancer, and 3.2 ± 2.7 years for lymphoma. PCPs already providing this care were willing to provide exclusive care sooner. The most useful modalities PCPs felt would assist them in assuming exclusive responsibility for follow-up cancer care were (1) a patient-specific letter from the specialist, (2) printed guidelines, (3) expedited routes of rereferral, and (4) expedited access to investigations for suspected recurrence. Conclusion With appropriate information and support in place, PCPs reported being willing to assume exclusive responsibility for the follow-up care of adult cancer survivors. Insights gained from this survey may ultimately help guide strategies in providing optimal care to these patients.
Molecularly-Imprinted Calcium Phosphate/Calcium Alginate Composite Microspheres by Surface Imprinting via Silane Crosslinking
Authors: Zhao Kongyin , Gao Ning , Liu Chao , Cheng Guoxiang 
Published: April 2009

This paper describes the development of a new type of molecularly-imprinted composite microspheres. Composite microspheres of calcium phosphate/calcium alginate (CP/CA CMs) were prepared from calcium phosphate and sodium alginate through the use of calcium chloride (CaCl2) as a gelling agent in an inverse suspension. Molecularly-imprinted calcium phosphate/calcium alginate composite microspheres (CP/CA MICMs) were then prepared by surface imprinting using CP/CA CMs as the supporting matrix, ethylene tri(β-methoxy)ethoxysilane (A-172) and γ-amidopropyltriethoxysilane (KH-550) as the functional monomers and crosslinking agents, respectively, and Methyl Orange as the template in aqueous solution. The CP/CA MICMs and non-imprinted composite microspheres (NICMs) were characterized by Fourier-transform infrared spectroscopy and optical microscopy. The adsorption behaviour of the CP/CA MICMs and NICMs were determined by ultraviolet spectrophotometry. The results indicated that molecular imprinting occurs via the crosslinking of silanes on the surface of the CP/CA CMs, and that CP/CA MICMs possess an adsorption capacity which exhibits greater selectivity. A schematic representation of the imprinting and recognition process of CA/CP MICMs by surface imprinting via silane crosslinking was presented.
Glossary of terms related to pharmaceutics (IUPAC Recommendations 2009)
Authors: Breuer Eli , Chorghade Mukund Shankar , Fischer János , Golomb Gershon 
Published: April 2009

Abstract
This Glossary of Terms in Pharmaceutics is needed by practitioners in the field of pharmaceutics as this field fulfills an important and crucial role, different from the roles of other scientific disciplines involved in the drug-making process. The glossary contains 168 definitions used in pharmaceutics. These are related to various aspects of this discipline such as: (1) physicochemical characterization of pharmaceutical preparations and the active ingredients they contain; (2) unit operations used in the practice of pharmaceutics; (3) terms related to the various dosage forms; (4) terms related to the various modes and routes of drug delivery; (5) terms used in pharmacokinetics and biopharmaceutics in general, and additional miscellaneous terms. The field of pharmaceutics itself is of a multidisciplinary nature as its practitioners come from a variety of disciplines, such as chemistry or various biological sciences, thus a glossary containing authoritative definitions would be useful for them. The terms used in pharmaceutics are rarely covered by existing glossaries, and in the cases they are, their definitions are often inappropriate for the field of pharmaceutics and require new or modified definitions to better fit the new context.
Glossary of terms used in ecotoxicology (IUPAC Recommendations 2009)
Authors: Nordberg Monica , Templeton Douglas M. , Andersen Ole , Duffus John Henderson 
Published: April 2009

AbstractThe objective of the "Glossary of Terms Used in Ecotoxicology" is to give clear definitions for those who contribute to studies relevant to ecotoxicology but are not themselves ecotoxicologists. This applies especially to chemists who need to understand the ecotoxicological literature without recourse to a multiplicity of dictionaries. The Glossary includes terms related to chemical speciation in the environment, sampling, monitoring and environmental analysis, as well as to adverse ecological effects of chemicals, ecological biomarkers, and the environmental distribution of chemicals. The dictionary consists of about 1139 terms. The authors hope that among the groups who will find this glossary helpful, in addition to chemists, are pharmacologists, toxicologists, ecotoxicologists, risk assessors, regulators, medical practitioners, and regulatory authorities. In particular, the glossary should facilitate the use of chemistry in relation to environmental risk assessment.
Self-Determination Skills and Opportunities of Adolescents With Severe Intellectual and Developmental Disabilities
Authors: Carter Erik W. , Owens Laura , Trainor Audrey A. , Sun Ye , Swedeen Beth 
Published: April 2009

AbstractWe asked teachers and parents to assess the self-determination prospects of 135 youth with severe intellectual and developmental disabilities. Teachers typically reported that youth evidenced limited knowledge about self-determined behavior, ability to perform these behaviors, and confidence regarding the efficacy of their self-determination efforts. Parents and teachers diverged in their evaluations of the self-determination capacities of youth but agreed that opportunities to engage in self-determined behavior were available both at school and home. Although social skill and problem behavior ratings both were significant predictors of teachers' ratings of students' self-determination capacity, opportunities at school, opportunities at home, and problem behaviors were negatively correlated with ratings of students' self-determination capacities and opportunities.
Finite Element Method Numerical Simulation of the Carburizing Process
Authors: Li Huiping , Zhao Guoqun , He Lianfang 
Published: April 2009

Abstract
Mathematical models of computing carbon content are given in this paper. To improve the computation accuracy of carbon content, lumped parameters and mesh refinement are used in the simulation process. Finite element method (FEM) software for simulating carbon content is developed using four-node quadrilateral isoparametric elements. For a circular gear and the cylinder, FEM simulation results of carburization are contrasted with those of the experiments and the comparisons show that the simulation results are consistent with the experimental results. The carburization depth, the relationship between carburization depth and carburizing time, and the influence of the geometrical shape of the part with respect to the carbon content were studied using FEM software.