Mechanisms of acquired resistance to trastuzumab‐based treatment in gastric cancer are largely unknown. In this study, we analyzed 22 pairs of tumor samples taken at baseline and post‐progression in ...patients receiving chemotherapy and trastuzumab for advanced HER2‐positive immunohistochemistry (IHC) 3+ or 2+ with in‐situ hybridization (ISH) amplification gastric or gastroesophageal cancers. Strict clinical criteria for defining acquired trastuzumab resistance were adopted. Loss of HER2 positivity and loss of HER2 over‐expression were defined as post‐trastuzumab IHC score <3+ and absence of ISH amplification, and IHC “downscoring” from 2+/3+ to 0/1+, respectively. HER2 IHC was always performed, while ISH was missing in 3 post‐progression samples. Patients with initial HER2 IHC score 3+ and 2+ were 14 (64%) and 8 (36%), respectively. Loss of HER2 positivity and HER2 over‐expression was observed in 32 and 32% samples, respectively. The chance of HER2 loss was not associated with any of the baseline clinicopathological variables. The only exception was in patients with initial IHC score 2+ versus 3+, for both endpoints of HER2 positivity (80 vs. 14%; p = 0.008) and HER2 over‐expression (63 vs. 14%; p = 0.025). As already shown in breast cancer, loss of HER2 may be observed also in gastric cancers patients treated with trastuzumab‐based chemotherapy in the clinical practice. This phenomenon may be one of the biological reasons explaining the failure of anti‐HER2 second‐line strategies in initially HER2‐positive disease.
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Patients with cancers positive for human epidermal growth factor receptor 2 (HER2) generally fail to respond to second‐line treatments, particularly when first‐line therapy included use of the HER2‐targeted agent trastuzumab. Post‐progression changes in HER2 expression, however, have not been studied extensively, and as a consequence, their therapeutic relevance is unclear. In this study, HER2 loss was associated with acquired resistance to trastuzumab in almost one‐third of patients with gastric or gastroesophageal cancers that initially were HER2‐positive. The findings suggest that after failure of trastuzumab, HER2 status should be reassessed prior to inclusion in clinical trials with targeted agents.
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•Successive amorphous layers of TiOx and FeOOH were electrodeposited.•The annealed amorphous layers were used as photoanodes in water splitting.•Charge carriers losses by ...recombination were reduced in TiO2-Fe2O3 heterostructure.•For comparative studies TiOx precursor was obtained by spin-coating.
Hematite-titania thin films with various ratios of Ti/Fe have been prepared on FTO substrate via cathodic and anodic deposition of amorphous Ti oxyhydroxide gel (TiOx) and iron oxyhydroxide (FeOOH) films, respectively followed by annealing processes. TiOx underlayer behaved as a template for FeOOH electrodeposition. The photocatalytic behavior of the photoanodes based on the prepared structures was studied. An increased photocurrent density was obtained without anodic shifting of the photocurrent onset potential. Mott-Schottky studies showed that Ti contributes little to donor density in hematite-titania photoanodes prepared by this technique. The impedance measurements suggest that both separation and transfer of charge carriers are promoted in these hematite-titania photoanodes. For comparative studies, hematite-titania photoanodes have been prepared from TiOx and FeOOH precursors formed by spin-coating technique and anodic deposition method, respectively. The photoelectrochemical performance of these photoanodes in the presence of cobalt-phosphate catalyst was also evaluated.
•Al13.45FeCrNiCo HEAs were synthesized successfully through liquid and solid state processes.•The processing method and annealing influenced the microstructure and properties of HEAs.•The ratio of ...FCC and BCC solid solutions of HEAs are changed after annealing.•All alloys revealed high hardness and a good mechanical behavior in compression.•The balance between mechanical strength and plastic deformation are kept even after annealing.
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The Al13.45FeCrNiCo high entropy alloys (HEAs) were obtained using two different processing routes, namely (i) mechanical alloying (MA) and spark plasma sintering (SPS), and (ii) vacuum induction melting – copper cast molding. A final homogenizing treatment step was applied to the as synthesized materials. Based on thermodynamic and empirical criteria for phase formation, the alloy was designed to develop a mixture of the face-centered-cubic (FCC) and body-centered-cubic (BCC) solid solution. The contribution of aluminum content on the alloy microstructure in terms of hardening of solid solution and precipitation hardening was highlighted. The influence of the processing route on the microstructure evolution and the relationship between the microstructure and properties of HEA materials were established by performing X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), and high-resolution (HR) TEM analyses, as well as microindentation and compression tests. The powder metallurgy processes produced a two-phase structure consisting of at least two types of crystalline grains based on FCC and BCC solid solutions. Increasing the sintering temperature from 950 °C to 1050 °C contributed to structural changes in the materials. Lower sintering temperatures (950 °C and 1000 °C) generated a single FCC phase structure, while at 1050 °C two FCC and BCC phases were obtained without any evidence of the liquid phase sintering. The as cast route generated a hypoeutectic type structure with a very fine and preferentially oriented dendritic structure, in which the interdendritic space is occupied by a second phase arranged in a network where the microstructure appears to be the result of a eutectic transformation with precipitation of secondary phases rich in Ni and Al. All the synthesized alloys revealed high hardness and a good mechanical behavior in compression. Sintered HEA materials exhibited higher Vickers hardness than as cast HEA, even after the heat treatment process, while the as cast HEA material has better ultimate strength and deformation behavior than sintered HEAs. The processing route did not affect the nature of the FCC and BCC solid solution phases formed in the Al13.45FeCrNiCo HEA materials but was responsible for the variation of phase proportion in the HEA’s microstructure, which in turn influenced the mechanical properties.
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•Lead acetate transparent film was prepared by spin coating on different substrates.•Lead acetate trihydrate film was used as precursor for perovskite film deposition.•Significant ...changes appear in perovskite structure after lead acetate dehydration.
This paper relates to a method for the preparation of lead acetate film and its use as precursor for two-step solution deposition of CH3NH3PbI3 perovskite film. For the preparation of perovskite film, lead acetate was used both in the form of trihydrate and dehydrated. The effects of lead acetate trihydrate dehydration on the structure of the resulted perovskite films were studied. The prepared perovskite films which consist of cuboid grains, show high surface coverage both on FTO and TiO2 substrates. XRD measurements have not revealed the presence of the PbI2 contaminant in perovskite film. Solvent vapor annealing method was employed to prepare perovskite film that contains lead iodide. Using impedance spectroscopy measurements, we further evaluated the influence of the prepared perovskite films on the performance of the photovoltaic devices.
Nanostructured hematite (α-Fe2O3) film deposited on mesoporous titania (TiO2) underlayer was described as a photoanode for photoelectrochemical water splitting. Mesoporous TiO2 layers were prepared ...by spin coating a paste on conductive fluorine-doped tin oxide glass followed by an annealing process. Hematite film was prepared after electrochemical and annealing processes. The TiO2/Fe2O3 photoanodes achieve photocurrent densities up to 0.5 mA/cm2 at 1.23 V versus reversible hydrogen electrode. This value is greater than that for photocurrent density obtained with pristine hematite photoanode. Impedance measurements showed that prepared heterostructure TiO2/Fe2O3 contributes to diminution of electron-hole recombination process.
•Mesoporous titania was used as template for hematite precursor electrodeposition.•The obtained composite films were used as photoanodes in water splitting.•The photoelectrochemical performance of these photoanodes was evaluated.•The most efficient photoanode has the thinnest mesoporous titania layer.
The role of second-line chemotherapy (CT) is not established in advanced biliary tract cancer (aBTC). We investigated the outcome of aBTC patients treated with second-line CT and devised a prognostic ...model.
Baseline clinical and laboratory data of 300 consecutive aBTC patients were collected and association with overall survival (OS) was investigated by multivariable Cox models.
The following parameters resulted independently associated with longer OS: Eastern Cooperative Oncology Group performance status of 0 (P<0.001; hazard ratio (HR), 0.348; 95% confidence interval (CI) 0.215-0.562), CA19.9 lower than median (P=0.013; HR, 0.574; 95% CI 0.370-0.891), progression-free survival after first-line CT ≥ 6 months (P=0.027; HR, 0.633; 95% CI 0.422-0.949) and previous surgery on primary tumour (P=0.027; HR, 0.609; 95% CI 0.392-0.945). We grouped the 249 patients with complete data available into three categories according to the number of fulfilled risk factors: median OS times for good-risk (zero to one factors), intermediate-risk (two factors) and poor-risk (three to four factors) groups were 13.1, 6.6 and 3.7 months, respectively (P<0.001).
Easily available clinical and laboratory factors predict prognosis of aBTC patients undergoing second-line CT. This model allows individual patient-risk stratification and may help in treatment decision and trial design.
This multicenter study evaluated three candidate microRNAs (miRNAs) (miR-21, miR-155 and miR-101) as potential biomarkers in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.
miRNA ...expression was quantified by quantitative RT-PCR in 86 laser-microdissected specimens, including 65 invasive IPMNs, 16 non-invasive IPMNs and 5 normal pancreatic ductal tissues. Univariate and multivariate analyses compared miRNAs and clinical parameters with overall (OS) and disease-free survival (DFS).
miR-21 and miR-155 were up-regulated in invasive IPMNs compared with non-invasive IPMNs, as well as in non-invasive IPMNs compared with normal tissues. Conversely, miR-101 levels were significantly higher in non-invasive IPMNs and normal tissues compared with invasive IPMNs. High levels of miR-21 were associated with worse OS hazard ratio (HR) = 2.47, 95% confidence interval (CI) = 1.37–5.65, P = 0.0047. Patients with high-miR-21 expression also had a shorter median DFS (10.9 versus 29.9 months, P = 0.01). Multivariate analysis confirmed miR-21 as independently prognostic for mortality and disease progression (death risk: HR = 3.3, 95% CI = 1.5–7.0, P = 0.02; progression risk: HR = 2.3, 95% CI = 1.2–4.8, P = 0.02), as well as positive lymph-node status (death risk: HR = 2.6, 95% CI = 1.1–6.3, P = 0.03; progression risk: HR = 2.2, 95% CI = 1.0–4.8, P = 0.04).
miR-21, miR-155 and miR-101 showed significant differences in invasive versus non-invasive IPMNs. miR-21 emerged as an independent prognostic biomarker in invasive IPMNs and should be validated in prospective studies.
The present study shows the results obtained in anodic electrodeposition of hematite precursor films in agarose gel template and photoelectrochemical characterization of the prepared hematite films. ...The peak current in cyclic voltammetry increases after each scan of the potential between −0.1 and 1.3 V for FTO electrode covered with a film of agarose gel in 0.1 M iron sulfate solution. The hematite samples with different thicknesses were prepared using template electrodeposition and annealing in air. The obtained nanostructured films were characterized by field emission scanning electron microscopy, X-ray diffraction, UV–vis spectroscopy, X-ray photoelectron spectroscopy and electrochemical impedance spectroscopy. The results show that a synergistic improvement of photocurrent density (1.14 mAcm−2 at 1.23 V vs RHE) is induced by Sn-doping and slight surface modification of hematite with thin and discontinuous NiO film. The results indicate that thicker hematite films and hematite films strongly modified with NiO nanostructures show a reduced photoactivity.
In a randomized trial with a median follow-up of 18.4 months, 6 months of induction chemotherapy with a three-drug regimen comprising 5-fluorouracil (by continuous infusion)-leucovorin, irinotecan, ...and oxaliplatin (FOLFOXIRI) demonstrated statistically significant improvements in response rate, radical surgical resection of metastases, progression-free survival, and overall survival compared with 6 months of induction chemotherapy with fluorouracil-leucovorin and irinotecan (FOLFIRI).
From November 14, 2001, to April 22, 2005, we enrolled 244 patients with metastatic colorectal cancer. To evaluate if the superiority of FOLFOXIRI is maintained in the long term, we updated the overall and progression-free survival data to include events that occurred up to February 12, 2009, with a median follow-up of 60.6 months. We performed a subgroup and a risk-stratified analysis to examine whether outcomes differed in specific patient subgroups, and we analyzed the results of treatment after progression. Survival curves were estimated by the Kaplan-Meier method. Multivariable Cox regression models were fit to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.
FOLFOXIRI demonstrated statistically significant improvements in median progression-free survival (9.8 vs 6.8 months, HR for progression = 0.59, 95% CI = 0.45 to 0.76, P < .001) and median overall survival (23.4 vs 16.7 months, HR for death = 0.74, 95% CI = 0.56 to 0.96, P = .026) with a 5-year survival rate of 15% (95% CI = 9% to 23%) vs 8% (95% CI = 4% to 14%). The improvements in progression-free survival and, to a lesser extent, in overall survival were evident even when the analysis excluded patients who received radical resection of metastases. With regard to the risk-stratified analysis, FOLFOXIRI results in longer progression-free survival and overall survival than FOLFIRI in all risk subgroups.
Six months of induction chemotherapy with FOLFOXIRI is associated with a clinically significant improvement in the long-term outcome compared with FOLFIRI with an absolute benefit in survival at 5 years of 7%.
The aim of this study was to evaluate the adhesion of different bioceramic coatings deposited by radio frequency magnetron sputtering on the biodegradable implant-type magnesium-calcium (MgCa) ...alloys. Hydroxyapatite (HA) and bioactive glass (BG) were chosen as coating materials, due to their remarkable biological potential. The morphology, composition, structure and adhesion of the deposited thin coatings was characterized by scanning electron microscopy, atomic force microscopy, energy dispersive X-ray spectroscopy, grazing incidence X-ray diffraction, Fourier transform infrared spectroscopy and pull-out adherence measurements. A variation of the coating-to-substrate adhesion has been recorded and correlated with the physico-chemical results. The bonding strength values of the coatings were promising (being superior to the ISO13779-2:2008 fabrication standard for load-bearing biomedical coatings), and thus, encourage us to further proceed with the biological evaluation of the HA or BG coatings-MgCa substrate couples.
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