In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus ...gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data.
LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R). Primary OS analysis was planned after ∼213 OS events and ≥32-month follow-up. OS was analysed by a Cox proportional hazards model, stratified by EGFR mutation type and baseline brain metastases.
Two-hundred and twenty-six OS events had occurred at the data cut-off (8 April 2016). After a median follow-up of 42.6 months, median OS (afatinib versus gefitinib) was 27.9 versus 24.5 months hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.66‒1.12, P = 0.2580. Prespecified subgroup analyses showed similar OS trends (afatinib versus gefitinib) in patients with exon 19 deletion (30.7 versus 26.4 months; HR, 0.83, 95% CI 0.58‒1.17, P = 0.2841) and L858R (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62‒1.36, P = 0.6585) mutations. Most patients (afatinib, 72.6%; gefitinib, 76.8%) had at least one subsequent systemic anti-cancer treatment following discontinuation of afatinib/gefitinib; 20 (13.7%) and 23 (15.2%) patients received a third-generation EGFR tyrosine kinase inhibitor. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib.
In LUX-Lung 7, there was no significant difference in OS with afatinib versus gefitinib. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib.
NCT01466660.
Aims
To demonstrate and characterize a portable lysis apparatus for rapid single‐step bacterial DNA extraction.
Methods and Results
Our portable lysis apparatus employed a novel design consisting of ...an annular piezo‐element with perforated diaphragm. Using Bacillus subtilis as target bacteria, our portable lysis apparatus was able to achieve a normalized percent lysis as high as 66% within 30 s. This is comparable to that by microprobe ultrasonication and almost 7 times higher than that by conventional bead beating. The effect from adding glass beads was predictable. However, the results from the addition of sodium dodecyl sulphate (SDS) were counter‐intuitive because a further increase from 0·5 to 1% concentration reduced the lysis performance. The portable lysis apparatus is also at least 1·5–5 times more power efficient than microprobe ultrasonication.
Conclusions
Our portable lysis apparatus is capable of rapidly extracting bacterial DNA and is more power efficient than microprobe ultrasonication. The addition of glass beads or SDS concentration (up to 0·5%) improves its performance.
Significance and Impact of the Study
The portable lysis apparatus provides a standalone, rapid, low cost and power efficient way of obtaining genomic constituents prior to a variety of bioassays used in the field of environmental, biomedical and other applied microbiology.
The aim of this study was to compare gene copy number (GCN) and protein expression of MET and to evaluate their prognostic roles in gastric carcinomas.
MET protein expression and gene amplification ...(GA) status were determined by immunohistochemistry (IHC) and silver in-situ hybridisation (SISH), respectively, in a large series of gastric carcinoma.
Protein overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in 10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381, respectively. Direct comparison revealed a significant correlation between high level of protein expression and increased GCN. All cases with GA showed protein overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could be categorised as GA according to the ASCO/CAP guideline for human epidermal growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated with poor prognosis.
MET IHC reflects well on GA, and therefore, it could be a primary screening test for patient selection for anti-MET therapy if GA is a major determinant of drug responsiveness. Also, the prognostic role of MET indicates that anti-MET therapy is a very promising modality in adjuvant treatment for gastric cancer.
Tumour-infiltrating lymphocytes (TILs) are known to be associated with response to primary systemic therapy (PST) in breast cancer. This study was conducted to assess the association of TIL subsets ...with pathological complete response (pCR) after PST in breast cancer in relation to breast cancer subtype, breast cancer stem cell (BCSC) phenotype and epithelial-mesenchymal transition (EMT).
The pre-chemotherapeutic biopsy specimens of 153 breast cancer patients who underwent surgical resection after anthracycline- or anthracycline/taxane-based PST were analysed. TIL subsets (CD4+, CD8+, and FOXP3+ TILs), BCSC phenotype, and the expression of EMT markers were evaluated by immunohistochemistry and were correlated with pCR after PST.
Infiltration of CD4+ and CD8+ T lymphocytes was closely correlated with BCSC phenotype and EMT. High levels of CD4+, CD8+, and FOXP3+ TILs were associated with pCR, and CD8+ TILs were found to be an independent predictive factor for pCR. In addition, CD8+ TILs were associated with pCR irrespective of breast cancer subtype, CD44+/CD24- phenotype, EMT, and chemotherapeutic regimen in subgroup analyses.
These findings indicate that CD8+ cytotoxic T lymphocytes are a key component of TILs associated with chemo-response and can be used as a reliable predictor of response to anthracycline- or anthracycline/taxane-based PST in breast cancer.
A memory cell consisting of a Pt/VO2/Pt switch element and a Pt/NiO/Pt memory element connected in series. By applying a voltage higher than Vth of 0.6 V, the switch element reaches the on state and ...the cell can be accessed. Since reset and set voltages are higher than Vth, information can be written by simply applying an appropriate voltage to a selected cell. By applying a voltage lower than Vth to the other cells, we can keep the other cells in the off state and prevent interference between the selected cell and the others.
Depression and anxiety (internalizing disorders) are the largest contributors to the non-fatal health burden among young people. This is the first meta-analysis to examine the joint efficacy of ...universal, selective, and indicated preventive interventions upon both depression and anxiety among children and adolescents (5-18 years) while accounting for their co-morbidity. We conducted a systematic review of reviews in Medline, PsycINFO and the Cochrane Library of Systematic Reviews, from 1980 to August 2014. Multivariate meta-analysis examined the efficacy of preventive interventions on depression and anxiety outcomes separately, and the joint efficacy on both disorders combined. Meta-regressions examined heterogeneity of effect according to a range of study variables. Outcomes were relative risks (RR) for disorder, and standardized mean differences (Cohen's d) for symptoms. One hundred and forty-six randomized controlled trials (46 072 participants) evaluated universal (children with no identified risk, n = 54) selective (population subgroups of children who have an increased risk of developing internalizing disorders due to shared risk factors, n = 45) and indicated prevention (children with minimal but detectable symptoms of an internalizing disorder, n = 47), mostly using psychological-only strategies (n = 105). Reductions in internalizing disorder onset occurred up to 9 months post-intervention, whether universal RR 0.47, 95% confidence interval (CI) 0.37-0.60, selective (RR 0.61, 95% CI 0.43-0.85) or indicated (RR 0.48, 95% CI 0.29-0.78). Reductions in internalizing symptoms occurred up to 12 months post-intervention for universal prevention; however, reductions only occurred in the shorter term for selective and indicated prevention. Universal, selective and indicated prevention interventions are efficacious in reducing internalizing disorders and symptoms in the short term. They might be considered as repeated exposures in school settings across childhood and adolescence. (PROSPERO registration: CRD42014013990.).
The study aims to determine whether type and density of tumour-infiltrating lymphocytes (TILs) can predict the clinical course in gastric cancer. Gastric carcinomas (n=220) were immunostained for ...CD3, CD8, CD20, and CD45RO and evaluated for clinicopathologic characteristics. Number of TILs that immunostained positively for each marker were counted using NIH ImageJ software. Tumours were grouped into low- and high-density groups for each marker (CD3, CD8, CD45RO). The densities of CD3(+), CD8(+), and CD45RO(+) TILs were found to be independent predictors of lymph node metastasis by multivariate analysis with odds ratios (95% CI) of 0.425 (0.204-0.885), 0.325 (0.150-0.707), and 0.402 (0.190-0.850), respectively. Kaplan-Meier survival analysis revealed that patients in the high-density groups for CD3, CD8, and C45RO had a significantly longer survival time than the patients in the corresponding low-density groups, respectively. In multivariate survival analysis, the densities of CD3(+), CD8(+), and CD45RO(+) TILs remained independent prognostic factors with hazard ratios (95% CI) of 0.549 (0.317-0.951), 0.574 (0.347-0.949), and 0.507 (0.298-0.862), respectively. In conclusion, density of TILs was found to be independently predictive of regional lymph node metastasis and patient survival in gastric cancer.
Methylation of the MGMT gene promoter is associated with a favorable prognosis in adult patients with GBM treated with TMZ. We determined the incidence of pseudoprogression according to the MGMT ...methylation status and the potential value of DSC perfusion MR images for predicting pseudoprogression.
New or enlarged enhancing lesions after CCRT in adult patients with newly diagnosed GBMs were prospectively assessed by measuring their rCBV by using DSC perfusion MR images. Tumor tissue was assayed to determine MGMT promoter methylation status. All patients were regularly followed up at an interval of 2 months by MR images, including DSC perfusion MR images.
Ninety eligible patients were enrolled in this study. After CCRT, new or enlarged enhanced lesions were found in 59 of 90 patients, which were subsequently classified as pseudoprogression (26 patients, 28.9%) and real progression (33 patients, 36.7%). Overall, there was a significant difference in the mean rCBV between pseudoprogression and real tumor progression (P = .003). The ROC curve revealed that an rCBV ratio >1.47 had an 81.5% sensitivity and a 77.8% specificity. The unmethylated MGMT promoter group had a significant difference of mean rCBV between pseudoprogression and real progression (P = .009), though the methylated MGMT promoter group had no significant difference (P = .258).
The current study suggests that rCBV measured by DSC perfusion MR images has a differential impact on the predictability of pseudoprogression in patients with GBM.
A quantum emitter efficiently coupled to a nanophotonic waveguide constitutes a promising system for the realization of single-photon transistors, quantum-logic gates based on giant single-photon ...nonlinearities, and high bit-rate deterministic single-photon sources. The key figure of merit for such devices is the β factor, which is the probability for an emitted single photon to be channeled into a desired waveguide mode. We report on the experimental achievement of β=98.43%±0.04% for a quantum dot coupled to a photonic crystal waveguide, corresponding to a single-emitter cooperativity of η=62.7±1.5. This constitutes a nearly ideal photon-matter interface where the quantum dot acts effectively as a 1D "artificial" atom, since it interacts almost exclusively with just a single propagating optical mode. The β factor is found to be remarkably robust to variations in position and emission wavelength of the quantum dots. Our work demonstrates the extraordinary potential of photonic crystal waveguides for highly efficient single-photon generation and on-chip photon-photon interaction.
MicroRNAs (miRNAs) are involved in tumorigenecity by regulating specific oncogenes and tumor suppressor genes, and their roles in breast cancer stem cells (BCSCs) are becoming apparent. Distinct from ...the CD44(+)/CD24(-/low) sub-population, we have isolated a novel PROCR(+)/ESA(+) BCSC sub-population. To explore miRNA-regulatory mechanisms in this sub-population, we performed miRNA expression profiling and found miR-495 as the most highly upegulated miRNA in PROCR(+)/ESA(+) cells. Coincidently, high upregulation of miR-495 was also found in CD44(+)/CD24(-/low) BCSCs, reflecting its potential importance in maintaining common BCSC properties. Ectopic expression of miR-495 in breast cancer cells promoted their colony formation in vitro and tumorigenesis in mice. miR-495 directly suppressed E-cadherin expression to promote cell invasion and inhibited REDD1 expression to enhance cell proliferation in hypoxia through post-transcriptional mechanism. miR-495 expression was directly modulated by transcription factor E12/E47, which itself is highly expressed in BCSCs. These findings reveal a novel regulatory pathway centered on miR-495 that contributes to BCSC properties and hypoxia resistance.
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