Polymers have been widely used for biomedical purposes such as medical devices, tissue engineering scaffolds, and drug carriers for drug delivery system (DDS). Using polymers for such medical devices ...should be entirely sensible, as polymers are generally very soft, highly cost-effective, and relatively biocompatible. In order to encourage further development in the biocompatibility of the polymers for the enhanced use of the materials, the functionalization of the polymer surfaces has been deliberately introduced. Plasma modification is one of the most efficient ways for the surface treatment of polymers, since plasma treatment could selectively modify the chemical and the physical properties of the surface of the polymers by not affecting the original bulk characteristics of the polymers. Also, plasma surface modification offers shorter treatment time as compared with other surface modification methods. When plasma was applied to the polymer surface, functional groups, graft polymerization, coatings, and molecular crosslinking formation would be introduced with or without the change in the surface roughness of the polymer. The highly functionalized polymers by the plasma modifications would be effectively used for the materials in tissue engineering or drug delivery systems. In this paper, the fabrication and the characterization of polymers by several types of plasma treatments are reviewed, followed by the introduction of their applications to the materials in drug delivery systems and tissue engineering.
•Studies on plasma treatments of polymers for biomedical applications are reviewed.•Achievements in biocompatibility by plasma treatments are discussed.•Plasma-modified polymeric surfaces were studied for structural characterization.•Biocompatibility and mechanical property of DLC-related coatings were summarized.•Plasma technique is a promising modification tool for DDS and tissue engineering.
Epidermal growth factor receptor (EGFR) mutation is predictive for the efficacy of EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer (NSCLC) treatment. We evaluated the ...performance, sensitivity, and concordance between five EGFR tests.
DNA admixtures (n = 34; 1%–50% mutant plasmid DNA) and samples from NSCLC patients 116 formalin-fixed paraffin-embedded (FFPE) tissue, 29 matched bronchofiberscopic brushing (BB) cytology, and 20 additional pleural effusion (PE) cytology samples were analyzed. EGFR mutation tests were PCR-Invader®, peptide nucleic acid-locked nucleic acid PCR clamp, direct sequencing, Cycleave™, and Scorpion Amplification Refractory Mutation System (ARMS)®. Analysis success, mutation status, and concordance rates were assessed.
All tests except direct sequencing detected four mutation types at ≥1% mutant DNA. Analysis success rates were 91.4%–100% (FFPE) and 100% (BB and PE cytology), respectively. Inter-assay concordance rates of successfully analyzed samples were 94.3%–100% (FFPE; kappa coefficients: 0.88–1.00), 93.1%–100% (BB cytology; 0.86–1.00), and 85.0%–100% (PE cytology; 0.70–1.00), and 93.1%–96.6% (0.86–0.93) between BB cytology and matched FFPE.
All EGFR assays carried out comparably in the analysis of FFPE and cytology samples. Cytology-derived DNA is a viable alternative to FFPE samples for analyzing EGFR mutations.
Electrophysiological techniques demonstrate abnormalities in somatosensory transmission, hence providing objective evidence of ‘somatosensory lesion or disease’ which is crucial to the diagnosis of ...neuropathic pain (NP). Since most instances of NP result from damage to thermo-nociceptive pathways (thin fibres and spino-thalamo-cortical systems), specific activation of these is critical to ensure diagnostic accuracy. This is currently achieved using laser pulses or contact heat stimuli, and in a near future probably also with contact cold and intra-epidermal low-intensity currents. Standard electrical stimuli, although of lesser diagnostic yield, are useful when large and small fibres are affected together. Nociceptive evoked potentials to laser (LEPs) and contact heat (CHEPs) have shown adequate sensitivity and specificity to be of clinical use in the differential diagnosis of NP, in conditions involving Aδ of C-fibres and spino-thalamo-cortical pathways. LEPs have also a role in the detection of patients at risk of developing central post-stroke pain after brainstem, thalamic or cortical injury. Cognitive cortical responses and autonomic reactions (sympathetic skin responses) reflect pain-related arousal and can document objectively positive symptoms such as allodynia and hyperalgesia. They are of help in the differential diagnosis of somatisation disorders, by discriminating conscious simulation (malingering) from conversive sensory loss. The electrophysiological approach to patients suspected, or at risk, of NP is a cost-effective procedure that should never be absent in the diagnostic armamentarium of pain clinics.
NEJ002 study, comparing gefitinib with carboplatin (CBDCA) and paclitaxel (PTX; Taxol) as the first-line treatment for advanced non-small cell lung cancer (NSCLC) harboring an epidermal growth factor ...receptor (EGFR) mutation, previously reported superiority of gefitinib over CBDCA/PTX on progression-free survival (PFS). Subsequent analysis was carried out mainly regarding overall survival (OS).
For all 228 patients in NEJ002, survival data were updated in December, 2010. Detailed information regarding subsequent chemotherapy after the protocol treatment was also assessed retrospectively and the impact of some key drugs on OS was evaluated.
The median survival time (MST) was 27.7 months for the gefitinib group, and was 26.6 months for the CBDCA/PTX group (HR, 0.887; P=0.483). The OS of patients who received platinum throughout their treatment (n=186) was not statistically different from that of patients who never received platinum (n=40). The MST of patients treated with gefitinib, platinum, and pemetrexed (PEM) or docetaxel (DOC, Taxotere; n=76) was around 3 years.
No significant difference in OS was observed between gefitinib and CBDCA/PTX in the NEJ002 study, probably due to a high crossover use of gefitinib in the CBDCA/PTX group. Considering the many benefits and the risk of missing an opportunity to use the most effective agent for EGFR-mutated NSCLC, the first-line gefitinib is strongly recommended.
Myxoid/round cell (RC) liposarcomas (MLS) were originally classified into two distinct populations based on histological differences; a myxoid component and a RC component. It is notable that, ...depending on an increase of the RC component, the prognosis significantly differs. Hence, the RC component is associated with metastasis and poor prognosis. However, the molecular mechanisms that contribute to the malignancy of the RC component still remain largely unknown. Here, we report microRNA-135b (miR-135b), a key regulator of the malignancy, highly expressed in the RC component and promoting MLS cell invasion in vitro and metastasis in vivo through the direct suppression of thrombospondin 2 (THBS2). Decreased THBS2 expression by miR-135b increases the total amount of matrix metalloproteinase 2 (MMP2) and influences cellular density and an extracellular matrix structure, thereby resulting in morphological change in tumor. The expression levels of miR-135b and THBS2 significantly correlated with a poor prognosis in MLS patients. Overall, our study reveals that the miR-135b/THBS2/MMP2 axis is tightly related to MLS pathophysiology and has an important clinical implication. This work provides noteworthy evidence for overcoming metastasis and improving patient outcomes, and sheds light on miR-135b and THBS2 as novel molecular targets for diagnosis and therapy in MLS.
Bulk crystals of electron-doped cuprates with a T′-type structure require both Ce substitutions and reduction annealing for the emergence of superconductivity while reduction annealing alone can ...induce superconductivity in thin films of T′-type cuprates. In order to reveal the low-energy electronic states which are responsible for the superconductivity, we have conducted angle-resolved photoemission spectroscopy measurements on thin films of the superconducting Ce-free T′-type cuprate Pr2CuO4. The results indicate that the overall band structure and the Fermi surface area of the superconducting Pr2CuO4 are similar to those of superconducting Ce-doped bulk single crystals, highlighting the importance of the actual electron concentration rather than the Ce concentration when discussing the physical properties of T′-type cuprates.
In order to investigate the electronic properties of the semiconducting van der Waals ferromagnet Cr2Ge2Te6 (CGT), where ferromagnetic layers are bonded through van der Waals forces, we have ...performed angle-resolved photoemission spectroscopy measurements and density-functional theory (DFT+U) calculations. The valence-band maximum at the Γ point is located ∼0.2eV below the Fermi level, consistent with the semiconducting property of CGT. Comparison of the experimental density of states with the DFT calculation has suggested that Coulomb interaction between the Cr 3d electrons Ueff∼1.1eV. The DFT+U calculation indicates that magnetic coupling between Cr atoms within the layer is ferromagnetic if Coulomb Ueff is smaller than 3.0 eV and that the interlayer coupling is ferromagnetic below Ueff∼1.0eV. We therefore conclude that, for Ueff deduced by the experiment, the intralayer Cr-Cr coupling is ferromagnetic and the interlayer coupling is near the boundary between ferromagnetic and antiferromagnetic, which means experimentally deduced Ueff is consistent with the theoretical ferromagnetic condition.
We update the Standard Model predictions of the anomalous magnetic moment of the muon,
a
μ
≡
(
g
−
2
)
/
2
, and the value of the QED coupling at the
Z-boson mass, incorporating the new
e
+
e
−
→
π
π
...data obtained by CMD-2 and KLOE, as well as the corrected SND data, and other improvements. The prediction for
a
μ
=
11659180.4
(
5.1
)
×
10
−10
is about
3
×
10
−10
lower than before, and has a smaller uncertainty, which corresponds to a 3.4
σ deviation from the measured value. The prediction for the QED coupling is
α
(
M
Z
2
)
−1
=
128.937
±
0.030
.
Plasma surface treatment was investigated as a surface modification method for a drug-eluting stent (DES) coated with polymers. Currently, the implantation of the DES is the most efficient way to ...treat a coronary artery disease. DES elutes anti-proliferative drugs that suppress proliferation of smooth muscle cells in the stented segment of the artery. Despite the impressive reduction in restenosis by DES, it still occasionally has a major disadvantage for not preventing restenosis at an implant site due to the relatively vast drug release from the stent surface in the early stages of the drug release. To solve the problem, we studied plasma treatments on the polymer surface because there would not be a substantial risk of damaging the bulk properties of the polymer and the stent by plasma surface treatments. In this study, argon, oxygen, and nitrogen were selected as working gases and poly(ethylene-co-vinyl acetate) (EVA), a hydrophobic biomedical polymer, was selected as a base drug-reservoir material for DES. Structural analyses were carried out by water contact angle measurements, X-ray photon spectroscopy (XPS), and the evaluation of the crosslinking degree of EVA polymer. It was found that the initial burst-release and the cumulative released amount of the drug were both effectively suppressed by controlling the plasma processing time. Furthermore, less effective control of the drug release was obtained by using nitrogen or oxygen plasma as a processing gas instead of argon plasma. According to the evaluation of the crosslinking degree, it was found that argon plasma could most effectively induce the crosslinking in EVA, while nitrogen and oxygen plasmas came in second and third, respectively, which corresponded to the results of the drug release experiments. It was expected that the experimental results of the plasma treatments could provide a new and alternative approach to a controllable and sustainable drug release system.
► Plasma treatment was introduced for the control of drug release from medical polymer. ► Reduction in drug release was observed by Ar, N2, and O2 plasma treatments. ► Most effective drug control was observed for Ar plasma-treated polymer. ► Ar plasma most effectively induced crosslinking on the surface of polymer. ► Degree of crosslinking in the polymer determined the drug release profile of polymer.
EGFR-TKI therapy produces a dramatic clinical response in patients with NSCLC harboring EGFR mutation. However, clinical outcomes should be improved further in this cohort. Thus, we conducted a ...randomized phase II study to investigate the efficacy and safety of combinational EGFR-TKI and chemotherapy, demonstrating that the combination might be a promising strategy for advanced EGFR-mutant NSCLC.
The first-line combination of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and platinum-based doublet chemotherapy has not been sufficiently evaluated for patients with EGFR-mutant non-small cell lung cancer (NSCLC). This randomized phase II study was designed to select a combination regimen for phase III evaluation.
Chemotherapy-naïve patients with advanced non-squamous, EGFR-mutant NSCLC were randomly assigned to receive either a concurrent or a sequential alternating regimen with gefitinib (250 mg) and carboplatin/pemetrexed area under the curve (AUC) = 6 and 500 mg/m2; 3-weekly. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), response, and safety.
All 80 patients enrolled were eligible and assessable for efficacy (41 and 39 patients in the concurrent and sequential alternating regimen groups, respectively). Median PFS was 18.3 months for the concurrent regimen and 15.3 months for the sequential alternating regimen hazard ratio (HR) 0.71 (0.42–1.20), P = 0.20. Although OS data are immature (16 and 24 death events), median survival times were 41.9 and 30.7 months in the concurrent and sequential alternating regimen groups, respectively HR 0.51 (0.26–0.99); P = 0.042. Response rates were similar in both groups (87.8% and 84.6%). Hematological and non-hematological adverse events were common and reversible; interstitial lung disease was neither frequent nor fatal (two cases in each group; 5% of all patients).
This is the first randomized study to investigate the efficacy of combinational EGFR-TKI and chemotherapy in the EGFR-mutated setting. Both regimens had promising efficacy with predictable toxicities, although concurrent regimens might provide better OS. The concurrent regimen was chosen to compare with gefitinib monotherapy in our ongoing phase III study.
University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN C000002789).
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