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1.
ACS Omega ; 9(7): 7923-7936, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38405542

ABSTRACT

Nanoparticles (NPs) have been proposed as additives to improve the rheological properties of polymer solutions and reduce mechanical degradation. This study presents the results of the retention experiment and the numerical simulation of the displacement efficiency of a SiO2/hydrolyzed polyacrylamide (HPAM) nanohybrid (CSNH-AC). The CSNH-AC was obtained from SiO2 NPs (synthesized by the Stöber method) chemically modified with HPAM chains. Attenuated total reflection-Fourier transform infrared spectroscopy, field emission gun-scanning electron microscopy, X-ray diffraction, and thermogravimetric analysis were used to characterize the nanohybrid. The injectivity and dynamic retention tests were performed at 56 °C in a sandstone core with a porosity of ∼26% and a permeability of 117 and 287 mD. A history matching of the dynamic retention test was performed to determine the maximum and residual adsorption, IPV, and residual resistance factor (RRF). A laboratory-scale model was used to evaluate the displacement efficiency of CSNH-AC and HPAM through numerical simulation. According to the results, the nanohybrid exhibits better rheological behavior than the HPAM solution at a lower concentration. The nanopolymer sol adsorption and IPV (29,7 µg/grock, 14,5) are greater than those of the HPAM solution (9,2 µg/grock, 10), which was attributed to the difference between the rock permeabilities used in the laboratory tests (HPAM: 287 mD and CSNH-AC: 117 mD). The RF of both samples gradually increases with the increase in shear rate, while the RRF slightly decreases and tends to balance. However, the nanopolymer sol exhibits greater RF and RRF values than that of the polymer solution due to the strong flow resistance of the nanohybrid (higher retention in the porous media). According to the field-scale simulation, the incremental oil production could be 295,505 and 174,465 barrels for the nanopolymer sol and the HPAM solution, respectively (compared to waterflooding). This will represent an incremental recovery factor of 11.3% for the nanopolymer sol and 6.7% for the HPAM solution.

2.
Nanomaterials (Basel) ; 14(2)2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38251121

ABSTRACT

Biopolymers emerge as promising candidates for enhanced oil recovery (EOR) applications due to their molecular structures, which exhibit better stability than polyacrylamides under harsh conditions. Nonetheless, biopolymers are susceptible to oxidation and biological degradation. Biopolymers reinforced with nanoparticles could be a potential solution to the issue. The nanofluids' stability and performance depend on the nanoparticles' properties and the preparation method. The primary objective of this study was to evaluate the effect of the preparation method and the nanoparticle type (SiO2, Al2O3, and TiO2) on the viscosity and stability of the scleroglucan (SG). The thickening effect of the SG solution was improved by adding all NPs due to the formation of three-dimensional structures between the NPs and the SG chains. The stability test showed that the SG + Al2O3 and SG + TiO2 nanofluids are highly unstable, but the SG + SiO2 nanofluids are highly stable (regardless of the preparation method). According to the ANOVA results, the preparation method and standing time influence the nanofluid viscosity with a statistical significance of 95%. On the contrary, the heating temperature and NP type are insignificant. Finally, the nanofluid with the best performance was 1000 ppm of SG + 100 ppm of SiO2_120 NPs prepared by method II.

3.
J Environ Manage ; 290: 112589, 2021 Jul 15.
Article in English | MEDLINE | ID: mdl-33906116

ABSTRACT

Agri-environment schemes (AES) are key mechanisms to deliver conservation policy, and include management to provide resources for target taxa. Mobile species may move to areas where resources are increased, without this necessarily having an effect across the wider countryside or on populations over time. Most assessments of AES efficacy have been at small spatial scales, over short timescales, and shown varying results. We developed a survey design based on orthogonal gradients of AES management at local and landscape scales, which will enable the response of several taxa to be monitored. An evidence review of management effects on butterflies, birds and pollinating insects provided data to score AES options. Predicted gradients were calculated using AES uptake, weighted by the evidence scores. Predicted AES gradients for each taxon correlated strongly, and with the average gradient across taxa, supporting the co-location of surveys across different taxa. Nine 1 × 1 km survey squares were selected in each of four regional blocks with broadly homogenous background habitat characteristics. Squares in each block covered orthogonal contrasts across the range of AES gradients at local and landscape scales. This allows the effects of AES on species at each scale, and the interaction between scales, to be tested. AES options and broad habitats were mapped in field surveys, to verify predicted gradients which were based on AES option uptake data. The verified AES gradient had a strong positive relationship with the predicted gradient. AES gradients were broadly independent of background habitat within each block, likely allowing AES effects to be distinguished from potential effects of other habitat variables. Surveys of several mobile taxa are ongoing. This design will allow mobile taxa responses to AES to be tested in the surrounding countryside, as well as on land under AES management, and potentially in terms of population change over time. The design developed here provides a novel, pseudo-experimental approach for assessing the response of mobile species to gradients of management at two spatial scales. A similar design process could be applied in other regions that require a standardized approach to monitoring the impacts of management interventions on target taxa at landscape scales, if equivalent spatial data are available.


Subject(s)
Agriculture , Butterflies , Animals , Biodiversity , Birds , Ecosystem , Environment
4.
Molecules ; 25(12)2020 Jun 22.
Article in English | MEDLINE | ID: mdl-32580500

ABSTRACT

In industry, silica nanoparticles (NPs) are obtained by the fuming and the precipitation method. Fumed silica NPs are commonly used in the preparation of nanocomposites because they have an extremely low bulk density (160-190 kg/m3), large surface area (50-600 m2/g), and nonporous surface, which promotes strong physical contact between the NPs and the organic phase. Fumed silica has fewer silanol groups (Si-OH) on its surface than the silica prepared by the Stöber method. However, the number of -OH groups on the fumed silica surface can be increased by pretreating them with sodium hydroxide (NaOH) before further surface modification. In this study, the effectiveness of the NaOH pretreatment was evaluated on commercial fumed silica NPs with a surface area of 200 m2/g. The number of surface -OH groups was estimated by potentiometric titration. The pretreated fumed NPs, and the precipitated NPs (prepared by the Stöber method) were modified with 3-aminopropyltriethoxysilane (APTES) to obtain A200S and nSiO2-APTES, respectively. The NPs were characterized using electron dispersive scanning (EDS), scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), BET (Brunauer-Emmett-Teller) analysis, and ζ-potential. XRD confirmed the presence of the organo-functional group on the surface of both NPs. After the amino-functionalization, the ζ-potential values of the nSiO2 and A200 changed from -35.5 mV and -14.4 mV to +26.2 mV and +11.76 mV, respectively. Consequently, we have successfully synthesized functionalized NPs with interesting, specific surface area and porosity (pore volume and size), which can be attractive materials for chemical and energy industries.


Subject(s)
Amines/chemistry , Nanoparticles/chemistry , Nanostructures/chemistry , Silicon Dioxide/chemistry , Dynamic Light Scattering , Nanoparticles/ultrastructure , Nanostructures/ultrastructure , Particle Size , Propylamines/chemistry , Silanes/chemistry , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
5.
Polymers (Basel) ; 12(5)2020 May 18.
Article in English | MEDLINE | ID: mdl-32443578

ABSTRACT

In this study, a set of advanced characterization techniques were used to evaluate the morphological, structural, and thermal properties of a novel molecular hybrid based on silica nanoparticles/hydrolyzed polyacrylamide (CSNH-PC1), which was efficiently obtained using a two-step synthetic pathway. The morphology of the nanohybrid CSNH-PC1 was determined using scanning electron microscopy (SEM), dynamic light scattering (DLS), and nanotracking analysis (NTA) techniques. The presence of C, N, O, and Si atoms in the nanohybrid structure was verified using electron dispersive scanning (EDS). Moreover, the corresponding structural analysis was complemented using powder X-ray diffraction (XRD) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR). The covalent bond between APTES-functionalized SiO2 nanoparticles (nSiO2-APTES), and the hydrolyzed polyacrylamide (HPAM) chain (MW ≈ 20.106 Da) was confirmed with high-resolution X-ray spectroscopy (XPS). Finally, the thermal properties of the nanohybrid were evaluated by using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The results showed that the CSNH-PC1 has a spherical morphology, with sizes between 420-480 nm and higher thermal resistance compared to HPAM polymers without modification, with a glass transition temperature of 360 °C. The integration of these advanced characterization techniques implemented here shows promising results for the study and evaluation of new nanomaterials with multiple applications.

6.
Mucosal Immunol ; 11(3): 681-692, 2018 05.
Article in English | MEDLINE | ID: mdl-29346347

ABSTRACT

Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103+CD11b+ (DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+CD11b- (SP) are not required for these responses. The lack of this response correlated with a complete absence of sFliC-specific plasma cells in the MLN, small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice expressed α4ß7+, suggesting a mucosal origin. Collectively, these results suggest that mucosal DP cDC contribute to the generation of the sFliC-specific plasma cell pool in the BM and thus serve as a bridge linking the mucosal and systemic immune system.


Subject(s)
Dendritic Cells/immunology , Interferon Regulatory Factors/metabolism , Lymph Nodes/immunology , Mucous Membrane/immunology , Plasma Cells/immunology , Animals , Antigens, CD/metabolism , CD11b Antigen/metabolism , Cells, Cultured , Flagellin/immunology , Immunity, Humoral , Immunoglobulin A/metabolism , Immunoglobulin Class Switching , Immunoglobulin G/metabolism , Integrin alpha Chains/metabolism , Integrin alpha4/metabolism , Integrin beta Chains/metabolism , Interferon Regulatory Factors/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout
7.
Radiography (Lond) ; 23 Suppl 1: S64-S69, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28780955

ABSTRACT

BACKGROUND: Peer-assisted learning provides a means through which individuals can learn from one another through a reciprocal process. Radiographic image interpretation skills are fundamental to both diagnostic radiography students and medical students due to their shared role in preliminary evaluation of conventional radiographic images. Medical students on graduation, may not be well prepared to carry out image interpretation, since evidence suggests that they perform less well than radiographers in e.g. Accident and Emergency situations. METHOD: A review of literature was conducted exploring the application of peer-assisted learning within diagnostic radiography and health education more widely as well as the practice of initial image interpretation. An extensive and systematic search strategy was developed which provided a range of material related to the areas. FINDINGS: An overview was obtained of the effectiveness of peer-assisted learning and the issues associated with development of image interpretation skills and a degree of discrepancy was identified between the two cohorts regarding their interpretative competence and confidence. This inconsistency may create an opportunity to apply peer-assisted learning, better preparing both disciplines for the practical application of image interpretation skills. CONCLUSION: The review identified the lack of a substantial evidence base relating to peer-assisted learning in radiography. Peer-assisted learning is not widely embraced in an interprofessional context. Multiple positive factors of such an intervention are identified which outweigh perceived negative issues. Student teacher and learner may benefit as should the clinical service from enhanced practitioner performance. The findings justify further research to develop the evidence base.


Subject(s)
Clinical Competence , Peer Group , Radiology/education , Technology, Radiologic/education , Humans , Interprofessional Relations , Learning
8.
Radiography (Lond) ; 23(3): 181-186, 2017 08.
Article in English | MEDLINE | ID: mdl-28687283

ABSTRACT

INTRODUCTION: The development of diagnostic imaging services manifests features specific to the Scottish environment, in particular development of the radiographic workforce through implementing skills mix and role developments to enhance outcomes for patients. A component of a College of Radiographers Industry Partnership Scheme (CoRIPS) supported study, this research investigates perspectives of strategic service managers with Health Board responsibility for service delivery. METHOD: A questionnaire survey was administered to strategic service managers across Scotland (N = 14), followed up with telephone interviews. There was a return rate of 57% (n = 8) for the questionnaires and n = 4 agreed to be interviewed. Data collected related to radiographer roles across their Board area; awareness and understanding of service development issues and features as well as perspective on opportunities and barriers in the context of Scottish Government policy, workforce logistics, attitudes and inter-professional relationships. RESULTS: The results indicate evidence of financial, logistical and political barriers to service evolution, offset by a sense of optimism that scope for beneficial change may be approaching. There are a range of significant initiatives in place and an appetite exists to pursue the development of radiographer roles and skill mix for the benefit of service users more generally. CONCLUSION: The difficulties in achieving change are well understood and there are basic issues related to finance and industrial relations. There are also however, cultural elements to contend with in the form of attitudes demonstrated by some radiographers and significantly, the radiological community whose influence on the practice of independently regulated radiographers seems incongruent.


Subject(s)
Allied Health Personnel/statistics & numerical data , Diagnostic Imaging , Job Description , Humans , Interviews as Topic , Scotland , Surveys and Questionnaires
10.
Reprod Domest Anim ; 51(2): 181-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26815482

ABSTRACT

To evaluate factors contributing to fertility of thoroughbred mares, data from 3743 oestrous periods of 2385 mares were collected on a large thoroughbred farm in Ireland. Fourteen stallions (mean age 8.3 years; range 4-15 years) had bred 2385 mares (mean age 9.4 years; range 3-24 years). Maiden mares accounted for 12%, mares with a foal at foot for 64%, and barren, slipped or rested mares for 24% of the total. The mean pregnancy rate per cycle was 67.8% (68.6% in year 1 and 66.9% in year 2). Backward stepwise multivariable logistic regression analysis was utilized to develop two models to evaluate mare factors, including mare age, reproductive status, month of foaling, dystocia, month of cover, foal heat, cycle number, treatments, walk-in status and stallion factors including stallion identity, stallion age, shuttle status, time elapsed between covers and high stallion usage on the per cycle pregnancy rate and pregnancy loss. Old age (p < 0.001) and cover within 20 days post-partum (p < 0.003) were associated with lowered pregnancy rates. High mare age (p < 0.05) and barren, slipped or rested reproductive status (p = 0.05) increased the likelihood of pregnancy loss. Uterine inflammation or infection, if appropriately treated, did not affect fertility. Only high usage of stallions (used more than 21 times in previous week) was associated with lowered (p = 0.009) pregnancy rates. However, shuttle stallions were more likely to have increased (p = 0.035) pregnancy survival, perhaps reflecting a bias in stallion selection. In conclusion, mare age exerted the greatest influence on fertility; nonetheless, thoroughbreds can be effectively managed to achieve high reproductive performance in a commercial setting.


Subject(s)
Horses/physiology , Infertility, Female/veterinary , Infertility, Male/veterinary , Pregnancy, Animal , Abortion, Veterinary , Aging , Animals , Female , Logistic Models , Male , Multivariate Analysis , Pregnancy , Pregnancy Rate , Risk Factors
12.
Vet Rec ; 170(21): 541, 2012 May 26.
Article in English | MEDLINE | ID: mdl-22535750

ABSTRACT

Deslorelin acetate implants, recently licensed in Ireland and the UK for ovulation induction in mares, have been associated with prolonged interovulatory intervals in USA studies, leading to the practice of removing implants postovulation. Trial data in Australia indicate a less pronounced effect on interovulatory intervals, suggesting possible geographical variation. Objectives of the current study were to assess the effect of deslorelin implants, with and without removal on oestrous cycle length in Irish- and UK-based Thoroughbred broodmares. Data were collected retrospectively from 88 oestrous cycles. A statistically significant difference (P=0.02) was found between interovulatory intervals in mares in which the deslorelin implant was not removed, compared with administration and removal of the implant or the use of human chorionic gonadotrophin. The results suggest that implant removal when possible is advisable. The delay in subsequent ovulations was less marked than that reported in some studies from the USA. This information is useful in deciding when to schedule subsequent breeding for mares which received a deslorelin implant during the previous oestrous period and provides evidence to counter-concerns that mares treated with deslorelin implants may experience a long delay in return to oestrus if the implant is not removed.


Subject(s)
Enzyme Inhibitors/pharmacology , Horses/physiology , Ovulation Induction/veterinary , Ovulation/drug effects , Triptorelin Pamoate/analogs & derivatives , Animals , Drug Implants , Estrus/drug effects , Estrus/physiology , Female , Ireland/epidemiology , Ovulation/physiology , Ovulation Induction/methods , Time Factors , Triptorelin Pamoate/pharmacology
13.
Oncology (Williston Park) ; 26(11): 1035, 1039, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23330342
14.
Clin Cancer Res ; 17(15): 5170-8, 2011 Aug 01.
Article in English | MEDLINE | ID: mdl-21693655

ABSTRACT

PURPOSE: p53 as a prognostic and predictive factor in early-stage breast cancer has had mixed results. We studied p53 protein expression, by immunohistochemistry, in a randomized clinical trial of stage II patients treated with adjuvant doxorubicin and cyclophosphamide with or without paclitaxel [Cancer and Leukemia Group B (CALGB) 9344, INT0148]. PATIENTS AND METHODS: Epithelial p53 expression was evaluated using two immunohistochemical antibodies (DO7 and 1801) in formalin-fixed, paraffin-embedded tissue from patients with node-positive breast cancer who were randomized to four cycles of cyclophosphamide and one of three doses of doxorubicin (60, 75, or 90 mg/m(2); AC) and to receive four subsequent cycles of paclitaxel (T) or not. Prognostic and predictive value of p53 protein expression was assessed, independent of treatment assignment, for escalating doses of doxorubicin or addition of T with endpoints of relapse-free (RFS) and overall survival (OS). RESULTS: Of 3,121 patients, 1,887 patient specimens treated on C9344 were obtained, passed quality control, and evaluated for p53 expression. Expression was 23% and 27% for mAbs 1801 and D07, respectively, with 92% concordance. In univariate analysis, p53 positivity was associated with worse OS with either antibody, but only p53 staining with monoclonal antibody 1801 had significantly worse RFS. In multivariate analysis, p53 was not predictive of RFS or OS from either doxorubicin dose escalation or addition of paclitaxel regardless of the antibody. CONCLUSION: Nuclear staining of p53 by immunohistochemistry is associated with worse prognosis in node-positive patients treated with adjuvant doxorubicin-based chemotherapy but is not a useful predictor of benefit from doxorubicin dose escalation or the addition of paclitaxel.


Subject(s)
Breast Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Adult , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cyclophosphamide/administration & dosage , Doxorubicin/therapeutic use , Female , Humans , Immunohistochemistry/methods , Lymphatic Metastasis , Middle Aged , Paclitaxel/administration & dosage , Predictive Value of Tests , Prognosis
15.
Oncology (Williston Park) ; 25(2): 115-24, 127, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21456382

ABSTRACT

Anthracycline-containing regimens improve disease-free and overall survival of patients with early breast cancer, but the toxicity, especially the cardiotoxicity, of the anthracyclines make them unattractive in the adjuvant setting. Two large, randomized trials, one in unselected patients and one in those with HER2-positive tumors, suggest that a taxane combination without an anthracycline might be just as effective as more traditional regimens. These and other studies also suggest that the anthracyclines might reasonably be used only for those with more aggressive forms of breast cancer, as defined by molecular markers. The results of these studies are provocative but insufficient to justify the conclusion that anthracyclines can be either abandoned or used only for a very select group of patients.


Subject(s)
Anthracyclines/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Age Factors , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , BRCA1 Protein/genetics , BRCA1 Protein/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Carboplatin/administration & dosage , Cyclophosphamide/administration & dosage , Female , Humans , Randomized Controlled Trials as Topic , Receptor, ErbB-2/metabolism , Taxoids/administration & dosage , Trastuzumab
16.
Mol Microbiol ; 78(4): 932-46, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20815824

ABSTRACT

The Bam complex is a highly conserved multiprotein machine essential for the assembly of ß-barrel outer membrane proteins. It is composed of the essential outer membrane protein BamA and four outer membrane associated lipoproteins BamB-E. The Yersinia enterocolitica Adhesin A (YadA) is the prototype of trimeric auotransporter adhesins (TAAs), consisting of a head, stalk and a ß-barrel membrane anchor. To investigate the role of BamA in biogenesis of TAAs, we expressed YadA in a BamA-depleted strain of Escherichia coli, which resulted in degradation of YadA. Yeast-two-hybrid experiments and immunofluorescence studies revealed that BamA and YadA interact directly and colocalize. As BamA recognizes the C-terminus of OMPs, we exchanged the nine most C-terminal amino acids of YadA. Substitution of the amino acids in position 1, 3 or 5 from the C-terminus with glycine resulted in DegP-dependent degradation of YadA. Despite degradation all YadA proteins assembled in the outer membrane. In summary we demonstrate that (i) BamA is essential for biogenesis of the TAA YadA, (ii) BamA interacts directly with YadA, (iii) the C-terminal amino acid motif of YadA is important for the BamA-dependent assembly and differs slightly compared with other OMPs, and (iv) BamA and YadA colocalize.


Subject(s)
Adhesins, Bacterial/metabolism , Amino Acids/metabolism , Bacterial Outer Membrane Proteins/metabolism , Escherichia coli Proteins/metabolism , Protein Multimerization , Yersinia enterocolitica/metabolism , Adhesins, Bacterial/genetics , Amino Acid Substitution/genetics , Amino Acids/genetics , Escherichia coli/genetics , Escherichia coli/metabolism , Mutagenesis, Site-Directed , Protein Binding , Protein Interaction Domains and Motifs , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Two-Hybrid System Techniques
18.
Int J Radiat Oncol Biol Phys ; 76(5): 1305-13, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19747781

ABSTRACT

PURPOSE: To report, from Cancer and Leukemia Group B Protocol 9082, the impact of high-dose cyclophosphamide, cisplatin, and BCNU (HD-CPB) vs. intermediate-dose CPB (ID-CPB) on the ability to start and complete the planned course of local-regional radiotherapy (RT) for women with breast cancer involving >or=10 axillary nodes. METHODS AND MATERIALS: From 1991 to 1998, 785 patients were randomized. The HD-CPB and ID-CPB arms were balanced regarding patient characteristics. The HD-CPB and ID-CPB arms were compared on the probability of RT initiation, interruption, modification, or incompleteness. The impact of clinical variables and interactions between variables were also assessed. RESULTS: Radiotherapy was initiated in 82% (325 of 394) of HD-CPB vs. 92% (360 of 391) of ID-CPB patients (p = 0.001). On multivariate analyses, RT was less likely given to patients who were randomized to HD treatment (odds ratio [OR] = 0 .38, p < 0.001), older (p = 0.005), African American (p = 0.003), postmastectomy (p = 0.02), or estrogen receptor positive (p = 0.03). High-dose treatment had a higher rate of RT interruption (21% vs. 12%, p = 0.001, OR = 2.05), modification (29% vs. 14%, p = 0.001, OR = 2.46), and early termination of RT (9% vs. 2%, p = 0.0001, OR = 5.35), compared with ID. CONCLUSION: Treatment arm significantly related to initiation, interruption, modification, and early termination of RT. Patients randomized to HD-CPB were less likely to initiate RT, and of those who did, they were more likely to have RT interrupted, modified, and terminated earlier than those randomized to ID-CPB. The observed lower incidence of RT usage in African Americans vs. non-African Americans warrants further study.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Adult , Aged , Analysis of Variance , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/ethnology , Breast Neoplasms/pathology , Canada , Carmustine/administration & dosage , Cisplatin/administration & dosage , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Lymphatic Metastasis , Middle Aged , Multivariate Analysis , Radiotherapy Dosage
19.
Lancet ; 374(9707): 2055-2063, 2009 Dec 19.
Article in English | MEDLINE | ID: mdl-20004966

ABSTRACT

BACKGROUND: Tamoxifen is standard adjuvant treatment for postmenopausal women with hormone-receptor-positive breast cancer. We assessed the benefit of adding chemotherapy to adjuvant tamoxifen and whether tamoxifen should be given concurrently or after chemotherapy. METHODS: We undertook a phase 3, parallel, randomised trial (SWOG-8814, INT-0100) in postmenopausal women with hormone-receptor-positive, node-positive breast cancer to test two major objectives: whether the primary outcome, disease-free survival, was longer with cyclophosphamide, doxorubicin, and fluorouracil (CAF) given every 4 weeks for six cycles plus 5 years of daily tamoxifen than with tamoxifen alone; and whether disease-free survival was longer with CAF followed by tamoxifen (CAF-T) than with CAF plus concurrent tamoxifen (CAFT). Overall survival and toxicity were predefined, important secondary outcomes for each objective. Patients in this open-label trial were randomly assigned by a computer algorithm in a 2:3:3 ratio (tamoxifen:CAF-T:CAFT) and analysis was by intention to treat of eligible patients. Groups were compared by stratified log-rank tests, followed by Cox regression analyses adjusted for significant prognostic factors. This trial is registered with ClinicalTrials.gov, number NCT00929591. FINDINGS: Of 1558 randomised women, 1477 (95%) were eligible for inclusion in the analysis. After a maximum of 13 years of follow-up (median 8.94 years), 637 women had a disease-free survival event (tamoxifen, 179 events in 361 patients; CAF-T, 216 events in 566 patients; CAFT, 242 events in 550 patients). For the first objective, therapy with the CAF plus tamoxifen groups combined (CAFT or CAF-T) was superior to tamoxifen alone for the primary endpoint of disease-free survival (adjusted Cox regression hazard ratio [HR] 0.76, 95% CI 0.64-0.91; p=0.002) but only marginally for the secondary endpoint of overall survival (HR 0.83, 0.68-1.01; p=0.057). For the second objective, the adjusted HRs favoured CAF-T over CAFT but did not reach significance for disease-free survival (HR 0.84, 0.70-1.01; p=0.061) or overall survival (HR 0.90, 0.73-1.10; p=0.30). Neutropenia, stomatitis, thromboembolism, congestive heart failure, and leukaemia were more frequent in the combined CAF plus tamoxifen groups than in the tamoxifen-alone group. INTERPRETATION: Chemotherapy with CAF plus tamoxifen given sequentially is more effective adjuvant therapy for postmenopausal patients with endocrine-responsive, node-positive breast cancer than is tamoxifen alone. However, it might be possible to identify some subgroups that do not benefit from anthracycline-based chemotherapy despite positive nodes. FUNDING: National Cancer Institute (US National Institutes of Health).


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents, Hormonal/administration & dosage , Breast Neoplasms/drug therapy , Lymph Nodes/pathology , Tamoxifen/administration & dosage , Adenocarcinoma/mortality , Adult , Aged , Antibiotics, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/mortality , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Lymphatic Metastasis , Middle Aged , Postmenopause , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis
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