A phantom study investigating the relationship between ground-glass opacity visibility and physical detectability index in low-dose chest computed tomography

In this study, the relationship between ground-glass opacity (GGO) visibility and physical detectability index in low-dose computed tomography (LDCT) for lung cancer screening was investigated. An anthropomorphic chest phantom that included synthetic GGOs with CT numbers of -630 Hounsfield units (HU; high attenuation GGO: HGGO) and -800 HU (low attenuation GGO: LGGO), and three phantoms for physical measurements were employed. The phantoms were scanned using 12 CT systems located in 11 screening centers in Japan. The slice thicknesses and CT dose indices (CTDIvol) varied over 1.0-5.0 mm and 0.85-3.30 mGy, respectively, and several reconstruction kernels were used. Physical detectability index values were calculated from measurements of resolution, noise, and slice thickness properties for all image sets. Five radiologists and one thoracic surgeon, blind to one another\u27s observations, evaluated GGO visibility using a five-point scoring system. The physical detectability index correlated reasonably well with the GGO visibility (R2 = 0.709, p vol. Consequently, the CTDIvol also correlated reasonably well with the GGO visibility (R2 = 0.701, p vol was nearly dominant in the GGO visibility for image sets with different reconstruction kernels and slice thicknesses, used in this study

Hochuekkito (TJ-41), a Kampo Formula, Ameliorates Cachexia Induced by Colon 26 Adenocarcinoma in Mice

Cachexia, a major cause of cancer-related death, is characterized by depletion of muscle and fat tissues, anorexia, asthenia, and hypoglycemia. Recent studies indicate that secretions of proinflammatory cytokines such as interleukin-6 (IL-6) play a crucial role in cachexia development, and that these cytokines are secreted from not only cancer cells but also host cells such as macrophages. In this study, we investigated the therapeutic effects of hochuekkito, a Kampo formula, on cachexia induced by colon 26 adenocarcinoma in mice. Hochuekkito treatment did not inhibit tumor growth, but significantly attenuated the reduction in carcass weight, food and water intake, weight of the gastrocnemius muscle and fat tissue around the testes, and decrease of serum triglyceride level compared with controls. Furthermore, hochuekkito treatment significantly reduced serum IL-6 level and IL-6 expression level in macrophages in tissues surrounding the tumor. In vitro studies showed that hochuekkito suppressed the production of IL-6 by THP-1 or RAW264.7 macrophage cells, although it did not affect IL-6 production by colon 26 carcinoma cells. These results suggest that hochuekkito inhibits the production of proinflammatory cytokines, particularly IL-6, by host cells such as macrophages. Therefore, hochuekkito may be a promising anticachectic agent for the treatment of patients with cancer

Role of FBXW7 in the quiescence of gefitinib-resistant lung cancer stem cells in EGFR-mutant non-small cell lung cancer

Several recent studies suggest that cancer stem cells (CSCs) are involved in intrinsic resistance to cancer treatment. Maintenance of quiescence is crucial for establishing resistance of CSCs to cancer therapeutics. F-box/WD repeat-containing protein 7 (FBXW7) is a ubiquitin ligase that regulates quiescence by targeting the c-MYC protein for ubiquitination. We previously reported that gefitinib-resistant persisters (GRPs) in EGFR-mutant non-small cell lung cancer (NSCLC) cells highly expressed octamer-binding transcription factor 4 (Oct-4) as well as the lung CSC marker CD133, and they exhibited distinctive features of the CSC phenotype. However, the role of FBXW7 in lung CSCs and their resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in NSCLC is not fully understood. In this study, we developed GRPs from the two NSCLC cell lines PC9 and HCC827, which express an EGFR exon 19 deletion mutation, by treatment with a high concentration of gefitinib. The GRPs from both PC9 and HCC827 cells expressed high levels of CD133 and FBXW7, but low levels of c-MYC. Cell cycle analysis demonstrated that the majority of GRPs existed in the G0/G1 phase. Knockdown of the FBXW7 gene significantly reduced the cell number of CD133-positive GRPs and reversed the cell population in the G0/G1-phase. We also found that FBXW7 expression in CD133-positive cells was increased and c-MYC expression was decreased in gefitinib-resistant tumors of PC9 cells in mice and in 9 out of 14 tumor specimens from EGFR-mutant NSCLC patients with acquired resistance to gefitinib. These findings suggest that FBXW7 plays a pivotal role in the maintenance of quiescence in gefitinib-resistant lung CSCs in EGFR mutation-positive NSCLC

Light-Triggered Adhesion of Water-Soluble Polymers with a Caged Catechol Group

An acrylamide-type copolymer containing hydroxyl, amino, and <i>ortho</i>-nitrobenzyl protected catechol groups was synthesized as a functional mussel adhesive protein (MAP) mimetic. The resulting copolymer was stable even in the oxidative condition. Light irradiation to aqueous solution of the copolymer induced deprotection of a caged compound to give a native catechol group and triggered an oxidative cross-linking reaction to afford the adhesive gel. Two glass plates were adhered through light-activated gelation of the polymer solution in a humid air atmosphere. A novel type of light-activated adhesive with excellent stability and light controllable activation properties was successfully fabricated by modification of the MAP mimetic copolymer

Asthma Control Can Be Maintained after Fixed-Dose, Budesonide/Formoterol Combination Inhaler Therapy is Stepped Down from Medium to Low Dose

Background: In cases using a budesonide/formoterol combination inhaler, many patients are started on fixed-dose treatment at 640/18 μg (4 puffs) daily, but there are no guidelines yet regarding the step-down method when control has been maintained. Methods: Patients with moderate asthma treated with either budesonide 400 μg and salmeterol 100 μg (GINA step3 group) or salmeterol/fluticasone 250 at 2 puffs (GINA step4 group) were enrolled and started on therapy of budesonide/formoterol 4 puffs. Thereafter, step-down to 2 puffs was performed if either of the following criteria was met at 8-week intervals: fractional exhaled nitric oxide (FeNO)≤28 ppb plus asthma control test (ACT) score≥22, or ACT score≥24 at 3 consecutive visits regardless of FeNO level. Thereafter, changes in ACT score, the number of acute exacerbations and reliever use, and FeNO level were monitored through 48th week. Results: Fifty-one patients, 27 in step3 group and 24 in step4 group, underwent step-down. ACT scores and the number of reliever use remained stable in both groups even after step-down. In contrast, FeNO levels increased gradually in step4 group, whereas in the step3 group they increased immediately after step-down. Step-down was considered to be safely performed because the numbers of reliever use and those of moderate or more severe exacerbations during the 48-week period has not changed significantly compared to before step-down. Conclusions: If complete control of asthma, not only of clinical symptoms but also airway inflammation, is achieved by 3-6 months of fixed-dose budesonide/formoterol 4 puffs/day, it should be possible to safely perform step-down to 2 puffs/day

Direct surface modification of poly(VDF-co-TrFE) films by surface-initiated ATRP without pretreatment

International audienceThe direct surface modification of poly(vinylidene fluoride-co-trifluoroethylene) (VDF-co-TrFE) copolymerfilms via surface-initiated atom transfer radical polymerization (ATRP) is presented. The surface-initiatedATRP of tert-butyl acrylate (tBA) and styrene was carried out on poly(VDF-co-TrFE) films containing 75mol% VDF at 383 K. Such a reaction was monitored by 1H and 19F NMR, attenuated total reflectanceFourier transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and by watercontact angle measurements. First, the 19F NMR spectra of poly(VDF-co-TrFE)-g-poly(tBA) graftcopolymers revealed a reduction in the signal intensity at 123 ppm compared with that of the poly(VDFco-TrFE) copolymer, indicating that the polymerization of tBA occurred exclusively by fluorine abstractionfrom the TrFE units. ATR-FTIR spectra of the resulting poly(VDF-co-TrFE)-g-poly(tBA) and poly(VDF-co-TrFE)-g-polystyrene (PS) films evidenced the characteristic absorption frequencies assigned to carbonyl andaromatic C–H stretching. The atomic ratio on the surface of polymer-grafted poly(VDF-co-TrFE) filmobserved by XPS well agreed with theoretical value of poly(tBA) and PS hompolymers. These resultsindicated that poly(tBA) and PS were successfully grafted onto the poly(VDF-co-TrFE) film surfaces forminggrafting layers, the thickness of which was over 10 nm. The poly(VDF-co-TrFE)-g-poly(tBA) film wassubsequently treated with p-toluenesulfonic acid and sodium hydrogen carbonate to modify the graftedchains into poly(acrylic acid sodium salt). Surface-grafted polystyrene was also converted to poly(styrenesulfonic acid sodium salt) by treatment with sulfonic acid. Each reaction step was characterized by ATR-IRand XPS. The static water contact angle of poly(VDF-co-TrFE) copolymer was remarkably reduced from 91to 15 by hydrolysis of the tBA chains, sulfonation of the styrene chains and their neutralization. Ahydrophilic surface was successfully achieved on the poly(VDF-co-TrFE) film by direct surface-initiatedpolymerization fromthe outermost surface of the TrFE unitwithout any change in the bulk physical properties