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Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma.Methods: This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety.Results: A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8-6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity.Conclusions: The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity. [ABSTRACT FROM AUTHOR]

Background: Peritoneal carcinomatosis is an increasingly common finding in gastric carcinoma. Previously, patients were treated as terminal, and median survival was poor. The use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in this context is still highly debatable. Objective: The aim of this study was to evaluate the long-term outcomes associated with CRS and HIPEC, and define prognostic factors for cure, if possible. Patients and Methods: All patients with gastric carcinomatosis from five French institutions who underwent combined complete CRS and HIPEC and had a minimum follow-up of 5 years were included in this study. Cure was defined as a disease-free interval of more than 5 years from the last treatment until the last follow-up. Results: Of the 81 patients who underwent CRS and HIPEC from 1989 to 2009, 59 had a completeness of cytoreduction score (CCS) of 0 (complete macroscopic resection), and the median Peritoneal Cancer Index (PCI) score was 6. Mitomycin C was the most commonly used drug during HIPEC (88 %). The 5-year overall survival (OS) rate was 18 %, with nine patients still disease-free at 5 years, for a cure rate of 11 %. All 'cured' patients had a PCI score below 7 and a CCS of 0. Factors associated with improved OS on multivariate analysis were synchronous resection ( p = 0.02), a lower PCI score ( p = 0.12), and the CCS ( p = 0.09). Conclusion: The cure rate of 11 % for patients with gastric carcinomatosis who are deemed terminal emphasizes that CRS and HIPEC should be considered in highly selected patients (low disease extent and complete CRS). [ABSTRACT FROM AUTHOR]

Background:The main objective of the present study was to establish the relationships between CA-125 kinetics and tumour size changes during treatment.Methods:The data from the CALYPSO-randomised phase III trial, comparing two platinum-based regimens in recurrent ovarian cancer (ROC) patients, was randomly split into a 'learning data set' to estimate model parameters and a 'validation data set' to validate model performances. A kinetic-pharmacodynamic semi-mechanistic model was built to describe tumour size and CA-125 kinetics during chemotherapy. The ability of the model to predict tumour response induced by chemotherapy, based on CA-125 values, was assessed.Results:Data from 535 ROC patients were used to model CA-125 kinetics and tumour size changes during the first 513 days after treatment initiation. Using the validated model, we could predict with accuracy the tumour size changes induced by chemotherapy based on the baseline imaging assessment and longitudinal CA-125 values (mean prediction error: 0.3%, mean absolute prediction error: 10.6%).Conclusions:Using a semi-mechanistic model, the dynamic relationships between tumour size changes and CA-125 kinetics induced by chemotherapy were established in ROC patients. A modelling approach allowed CA-125 to be assessed as a biomarker for tumour size dynamics, to predict treatment efficacy for research and clinical purposes. [ABSTRACT FROM AUTHOR]

Purpose: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare primary peritoneal malignancy. Its prognosis has been improved by an aggressive locoregional treatment combining extensive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic factors are currently poorly defined for this disease but are essential if treatment is to be standardized. Methods: Twenty-eight patients with DMPM, who were considered preoperatively to be candidates for CRS and HIPEC between June 1998 and August 2010 at our institution, were selected for this study. Medical records and histopathological features were retrospectively reviewed and 24 clinical, histological, and immunohistochemical parameters were assessed for their association with overall survival by univariate and multivariate analyses. Results: The following factors were significantly associated with overall survival by univariate analysis: predominant histological growth pattern in the epithelioid areas, nuclear grooves in the epithelioid areas, atypical mitoses, and calretinin and GLUT1 expression by immunohistochemistry in the epithelioid areas. Expression of the facilitative glucose transporter protein GLUT1 in the epithelioid areas was the only factor independently associated with overall survival by multivariate analysis. Conclusions: GLUT1 expression appears to be an indicator of poor prognosis in DMPM. Standard histological classification of DMPM may not be adequate to select patients for aggressive locoregional treatments, such as CRS and HIPEC. Multicenter validation of the prognostic factors identified in this preliminary study is needed to refine patient selection for potential cure. [ABSTRACT FROM AUTHOR]

Background:In low-risk gestational trophoblastic neoplasia (GTN) patients, a predictive marker for early identification of methotrexate (MTX) resistance would be useful. We previously demonstrated that kinetic modelling of human chorionic gonadotrophin (hCG) measurements could provide such a marker. Here we validate this approach in a large independent patient cohort.Methods:Serum hCG measurements of 800 low-risk GTN patients treated with MTX were analysed. The cohort was divided into Model and Test data sets. hCG kinetics were described from initial treatment day to day 50 using: '(hCG(time))=hCG0*exp(-k*time)+hCGres', where hCGres is the modelled residual production, hCG0 is the baseline hCG level, and k is the rate constant. HCGres-predictive value was investigated against previously reported predictors of MTX resistance.Results:Declining hCG measurements were well fitted by the model. The best discriminator of MTX resistance in the Model data set was hCGres, categorised by an optimal cut-off value of >20.44 IU l−1: receiver-operating characteristic (ROC) area under the curve (AUC)=0.87; Se=0.91; Sp=0.83. The predictive value of hCGres was reproducible using the Test data set: ROC AUC=0.87; Se=0.88; Sp=0.86. Multivariate analyses revealed hCGres as a better predictor of MTX resistance (HR=1.01, P<0.0001) and MTX failure-free survival (HR=13.25, P<0.0001) than other reported predictive factors.Conclusion:hCGres, a modelled kinetic parameter calculated after fully dosed three MTX cycles, has a reproducible value for identifying patients with MTX resistance. [ABSTRACT FROM AUTHOR]

Background:This phase I cohort study investigated aflibercept (vascular endothelial growth factor (VEGF) trap) plus docetaxel and cisplatin in patients with advanced solid tumours.Methods:Patients received intravenous aflibercept 4, 5, or 6 mg kg−1 with docetaxel and cisplatin (75 mg m−2 each) on day 1 of a 3-week cycle until progressive disease or unacceptable toxicity. Primary objectives were determining cycle 1 dose-limiting toxicities (DLTs) and the aflibercept recommended phase II trial dose (RP2D) for this combination.Results:During the dose-escalation phase (n=16), there were two DLTs of febrile neutropenia (at 4 and 5 mg kg−1). Granulocyte colony-stimulating factor prophylaxis was subsequently recommended. The RP2D of aflibercept was established at 6 mg kg−1 and administered to 14 additional patients. The most frequent grade 3/4 adverse events (AEs) were neutropenia (43.3%), stomatitis (20.0%), asthenia/fatigue (20.0%), and hypertension (16.7%). All-grade AEs associated with VEGF blockade included epistaxis (83.3%), dysphonia (70.0%), proteinuria (53.3%), and hypertension (50.0%). There were five partial responses (16.7%) and 18 cases of stable disease (60.0%) (lasting >3 months in 10 patients). There were no pharmacokinetic (PK) interactions between the three drugs.Conclusion:Aflibercept 6 mg kg−1 with docetaxel and cisplatin 75 mg m−2 every 3 weeks is the RP2D based on tolerability, antitumour activity, and PKs. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate antitumor effects of cyclooxygenase-2 inhibitors in breast carcinoma and their ability to act synergistically with aromatase inhibitors (AIs). Postmenopausal metastatic breast cancer patients without previous adjuvant AI treatment received exemestane 25 mg/days plus either celecoxib 400 mg twice daily or placebo. The primary endpoint was progression-free survival (PFS). This trial was prematurely terminated ( N = 157 of 342 planned) after cardiovascular toxicity was reported in other celecoxib trials. Although no PFS difference was observed between the two arms (9.8 months for both, P = 0.72), a trend favoring celecoxib was observed in 60 tamoxifen-resistant patients (9.6 vs. 5.1 months; P = 0.14) and in 126 patients treated ≥3 months before study termination (12.2 vs. 9.8 months; P = 0.09). No severe adverse events were reported. Cyclooxygenase-2 inhibitors seemingly contribute to reverse endocrine resistance in breast cancer patients, although further study is necessary to allow development of a new therapeutic strategy. [ABSTRACT FROM AUTHOR]

Recently, technologies for twin-roll casting have been widely developed to efficiently fabricate the lightweight Mg alloy sheets that are quite attractive for numerous weight-sensitive applications. This paper reviews the recent progress in the twin-roll casting of Mg alloys, focusing on the processing aspects that have close relations to the solidification behavior of Mg alloy strips. In addition, recent attempts to develop new Mg alloys utilizing the metallurgical advantages attainable by this novel casting process are also presented. [ABSTRACT FROM AUTHOR]

The correlation of the equilibrium behaviors of phosphorus and vanadium between slag and low carbon molten steel in inert atmosphere was investigated with respect to the experimental variables of slag basicity, the (P2O5) and (V2O5) content, and the reaction temperature. The distribution ratios of phosphorus and vanadium increased with an increase in the slag basicity. The logarithms of the vanadium distribution ratio were greater by a factor of about two than those of phosphorus in the range of low slag basicity, but the difference diminished with an increase in the slag basicity. The logarithms of the vanadium distribution ratio increased linearly with an increase in the (P2O5) and (V2O5) content in the slag, while those of phosphorus remained nearly constant. The logarithms of the phosphorus and vanadium distribution ratio decreased with an increase in temperature, and the dependence on temperature was greater for the phosphorus than for the vanadium. For both the maximization of the vanadium yield and the minimization of the rephosphorization of molten steel in the steelmaking process, the ratio of N(V2O5)/N(P2O5), the slag basicity, the ratio of f[P]/f[V], and the temperature should be maximized, and the (FeO) content in the slag should be minimized. [ABSTRACT FROM AUTHOR]

The effects of melt temperature and mold preheating temperature on the fluidity of Ca containing AZ31 alloys were evaluated under various casting conditions. The flow lengths of AZ31-xCa alloy melt increased with increasing the melt temperature due to lower viscosity and longer time to fill the mold cavity. The increment of the flow lengths of AZ31-xCa alloy melt with increasing the mold preheating temperature was not large due to large diameter of circular cross section of mold cavity. The fluidity of AZ31-xCa alloy melts was affected more forcefully by melt temperature than by mold preheating temperature under casting conditions used in this study. Also, the flow lengths of AZ31-xCa alloy melt were affected by grain size of primary solid particles solidified during filling mold cavity and surface oxide film due to addition of Ca. [ABSTRACT FROM AUTHOR]

A new method to measure thresholds of electron-stimulated desorption (ESD) for neutral particles by means of energy-modulated electron beams is introduced. As examples of this new method, thresholds of ESD for neutral particles of N2 and O2 from the surfaces of polycrystalline Ni, Mo, and W are measured. Compared with the method via non-modulated electron beams, the instrument of measurement is simplified. Moreover, thresholds of ESD can be directly measured in high vacuum. [ABSTRACT FROM AUTHOR]

A new method to measure thresholds of electron-stimulated desorption (ESD) for neutral particles by means of energy-modulated electron beams is introduced. As examples of this new method, thresholds of ESD for neutral particles of N2 and O2 from the surfaces of polycrystalline Ni, Mo, and W are measured. Compared with the method via non-modulated electron beams, the instrument of measurement is simplified. Moreover, thresholds of ESD can be directly measured in high vacuum. [ABSTRACT FROM AUTHOR]

The temperature dependence of the Hall mobility, Seebeck coefficient, electrical resistivity, thermal conductivity, and figure-of-merit of the SbI3 and CuBr-doped 85% Bi2Te3-15% Bi2Se3 single crystals have been characterized at temperatures ranging from 77 K to 600 K. The scattering parameter in 85% Bi2Te3-15% Bi2Se3 single crystal was determined as 0.1 from the temperature dependence of the carrier mobility. With increasing the amount of Sbl3 or CuBr doping, the Seebeck coefficient of 85% Bi2Te3-15% Bi2Se3 decreased and the temperature at which the Seebeck coefficient shows a maximum shifted to higher temperature. Compared to the Sbl3-doped specimens, the CuBr-doped single crystals exhibited higher (m* / m0)3/2 μc, implying that CuBr is a more effective dopant to improve the material factor and thus the figure-of-merit of 85% Bi2Te3-15% Bi2Se3. The maximum figure-of-merit of 2.0 × 10−3/K and 2.2 × 10−3/K was obtained for 0.1 wt % Sbl3-doped specimen and 0.03 wt % CuBr-doped specimen, respectively. [ABSTRACT FROM AUTHOR]

A 3.5 nm amorphous CoFeB film was sputtered on GaAs (001) wafer substrate without applying magnetic field during deposition, and a significant in-plane uniaxial magnetic anisotropy (UMA) field (Hu) of about 300 Oe could be achieved. To precisely determine the intrinsic Gilbert damping constant (α) of this film, both ferromagnetic resonance (FMR) and time-resolved magneto-optical Kerr effect (TRMOKE) techniques were utilized. With good fitting of the dynamic spectra of FMR and TRMOKE, α is calculated to be 0.010 and 0.013, respectively. Obviously, the latter is 30% larger than the former, which is due to the transient heating effect during the TRMOKE measurement. In comparison with ordinary amorphous CoFeB films with negligible magnetic anisotropies, α is enhanced significantly in the CoFeB/GaAs(001) film, which may be mainly resulted from the enhanced spin-orbit coupling induced by the CoFeB/GaAs interface. However, the significant in-plane UMA plays minor role in the enhancement of α. [ABSTRACT FROM AUTHOR]

We report on the experimental and theoretical studies of cooling field (HFC) and temperature (T) dependent exchange bias (EB) in FexAu1 − x/Fe19Ni81 spin glass (SG)/ferromagnet (FM) bilayers. When x varies from 8% to 14% in the FexAu1 − x SG alloys, with increasing T, a sign-changeable exchange bias field (HE) together with a unimodal distribution of coercivity (HC) are observed. Significantly, increasing in the magnitude of HFC reduces (increases) the value of HE in the negative (positive) region, resulting in the entire HE ∼ T curve to move leftwards and upwards. In the meanwhile, HFC variation has weak effects on HC. By Monte Carlo simulation using a SG/FM vector model, we are able to reproduce such HE dependences on T and HFC for the SG/FM system. Thus this work reveals that the SG/FM bilayer system containing intimately coupled interface, instead of a single SG layer, is responsible for the novel EB properties. [ABSTRACT FROM AUTHOR]

Low dimensional nanostructures have attracted attention due to their rich physical properties and potential applications. The essential factor for their functionality is their electronic properties, which can be modified by quantum confinement. Here the electronic states of Gd atom trapped in open Fe corrals on Ag(111) were studied via scanning tunneling spectroscopy. A single spectroscopic peak above the Fermi level is observed after Gd adatoms are trapped inside Fe corrals, while two peaks appear in empty corrals. The single peak position is close to the higher energy peak of the empty corrals. These findings, attributed to quantum confinement of the corrals and Gd structures trapped inside, are supported by tight-binding calculations. This demonstrates and provides insights into atom trapping in open corrals of various diameters, giving an alternative approach to modify the properties of nano-objects. [ABSTRACT FROM AUTHOR]