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1.
J Phys Chem B ; 128(18): 4537-4543, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38683761

RESUMO

The anion-selective transport through subnanoporous liquid-crystalline (LC) water treatment membranes was quantitatively detected by the deposition and electrochemical analysis of the LC membrane on the GaN electrode. The time course of the capacitance and Warburg resistance of the LC membrane suggest that the interaction of the LC membrane with monovalent Cl- ions is distinctly different from that with SO42- ions. A continuous decay in capacitance suggests the condensation of Cl- ions in subnanopores, whereas the interaction between SO42- ions and the inner wall of subnanopores is much weaker. The chronoamperometry data further suggest that SO42- ions are transported through subnanoporous channels 10 times faster than Cl- ions. These results, together with the previous X-ray emission spectroscopy, suggest that SO42- ions, which possess similar hydrogen-bonded structures to the hydrogen-bonded networks inside the subnanopores, can exchange the associated water molecules and hop along the network of water molecules, but Cl- ions bind and accumulate inside subnanopores. The well-controlled supramolecular self-assembly of LC building blocks opens a large potential toward the fine adjustment of hydrogen-bonding networks in nanospace providing materials new functions, which cannot be realized by bulk water.

2.
J Phys Chem Lett ; 15(2): 454-460, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38189793

RESUMO

Here, we report a synchrotron-based high-resolution soft X-ray emission spectroscopy study on hydrogen-bonded structures of water molecules in the self-organized, hydroxy-group-functionalized one-dimensional nanochannels of liquid crystalline nanostructured membranes. The water molecules confined in the uncharged hydroxy-functionalized nanochannels (which have a diameter of about 1.5 nm) exhibit hydrogen-bonded structures close to those of bulk liquid water, even directly interacting with diol groups. These hydrogen-bonded structures contrast with the more distorted hydrogen bonding of water molecules confined in self-organized channels with a diameter of 0.6 nm formed by an analogous nanostructured membrane with a cationic moiety, which was explained by the ability of the channel functional groups to donate and accept hydrogen bonds in a confined space and the nanochannel diameter.

3.
Int J Mol Sci ; 24(11)2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37298615

RESUMO

Tissue plasminogen activator, aiming to restore cerebral blood flow (CBF), has been used for acute ischemic strokes in clinics; however, its narrow therapeutic time window remains a serious concern. To develop novel prophylactic drugs to alleviate cerebral ischemia/reperfusion injuries, ferulic acid derivative 012 (FAD012) was synthesized and showed comparable antioxidant properties to ferulic acid (FA) and probably possesses the potent ability to cross the blood-brain barrier. A more potent cytoprotective effect of FAD012 against H2O2-induced cytotoxicity in PC12 cells was also observed. In vivo toxicity was not observed in rats given a long-term oral administration of FAD012, indicating its good tolerability. A one-week-course oral administration of FAD012 significantly alleviated middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injuries in rats, accompanied by the restoration of CBF and endothelial nitrogen oxide synthetase (eNOS) expression. Treatment with FAD012 significantly restored the cell viability and eNOS expression damaged by H2O2, used to mimic MCAO-triggered oxidative stress, in rat brain microvascular endothelial cells. Our findings suggested that FAD012 protected the viability of vascular endothelium and maintained eNOS expression, ultimately contributing to the restoration of CBF, and may provide a rationale for the development of FAD012 into an effective prophylactic drug for patients at high risk of stroke.


Assuntos
Isquemia Encefálica , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Animais , Ratos , Isquemia Encefálica/tratamento farmacológico , Circulação Cerebrovascular , Células Endoteliais/metabolismo , Peróxido de Hidrogênio/uso terapêutico , Infarto da Artéria Cerebral Média/metabolismo , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico Sintase , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Ativador de Plasminogênio Tecidual/uso terapêutico
4.
Spine (Phila Pa 1976) ; 48(24): 1741-1748, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36763826

RESUMO

STUDY DESIGN: A multicenter retrospective study. OBJECTIVE: This study aimed to elucidate the incidence and risk factors of lateral cage migration (LCM) after lateral lumbar interbody fusion (LLIF) combined with posterior instrumentation. SUMMARY OF BACKGROUND DATA: LLIF has recently become a widely accepted procedure for the treatment of lumbar degenerative diseases. Although LLIF complications include vascular, nerve, and abdominal organ injuries, few studies have identified specific risk factors for LCM after LLIF. MATERIALS AND METHODS: Between January 2015 and December 2020, 983 patients with lumbar degenerative diseases or osteoporotic vertebral fractures underwent LLIF combined with posterior instrumentation. The fusion sites were located within the lumbosacral lesions. LCM was defined as a change of >3 mm in the movement of the radiopaque marker on radiographs. The patients were classified into LCM and non-LCM groups. Medical records and preoperative radiographs were also reviewed. The 1:5 nearest-neighbor propensity score matching technique was used to compare both groups, and radiologic parameters, including preoperative disk height (DH), preoperative sagittal disk angle, disk geometry, height variance (cage height minus DH), and endplate injury, were analyzed to identify the factors influencing LCM incidence. RESULTS: There were 16 patients (1.6%) with LCM (10 men and 6 women; mean age 70.1 yr). The Cochran-Armitage trend test showed a linear trend toward an increased rating of LCM with an increasing number of fused segments ( P =0.003), and LCM occurred at the terminal cage-inserted disk level in all patients in the LCM group. After propensity-matched analysis, we identified high DH ( P <0.001), large sagittal disk angle ( P =0.009), round-type disk ( P =0.008), and undersized cage selection ( P <0.001) as risk factors for LCM. CONCLUSION: We identified risk factors for LCM after LLIF combined with posterior instrumentation. To avoid this complication, it is important to select the appropriate cage sizes and enhance posterior fixation for at-risk patients.


Assuntos
Vértebras Lombares , Fusão Vertebral , Masculino , Humanos , Feminino , Idoso , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Fatores de Risco , Radiografia
5.
Molecules ; 27(19)2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36235115

RESUMO

The cytotoxicity of a trivalent arsenic derivative (arsenite, AsIII) combined with arenobufagin or gamabufotalin was evaluated in human U-87 glioblastoma cells. Synergistic cytotoxicity with upregulated intracellular arsenic levels was observed, when treated with AsIII combined with arenobufagin instead of gamabufotalin. Apoptosis and the activation of caspase-9/-8/-3 were induced by AsIII and further strengthened by arenobufagin. The magnitude of increase in the activities of caspase-9/-3 was much greater than that of caspase-8, suggesting that the intrinsic pathway played a much more important role in the apoptosis. An increase in the number of necrotic cells, enhanced LDH leakage, and intensified G2/M phase arrest were observed. A remarkable increase in the expression level of γH2AX, a DNA damage marker, was induced by AsIII+arenobufagin. Concomitantly, the activation of autophagy was observed, suggesting that autophagic cell death associated with DNA damage was partially attributed to the cytotoxicity of AsIII+arenobufagin. Suppression of Notch signaling was confirmed in the combined regimen-treated cells, suggesting that inactivation of Jagged1/Notch signaling would probably contribute to the synergistic cytotoxic effect of AsIII+arenobufagin. Given that both AsIII and arenobufagin are capable of penetrating into the blood-brain barrier, our findings may provide fundamental insight into the clinical application of the combined regimen for glioblastoma.


Assuntos
Antineoplásicos , Arsênio , Arsenitos , Bufanolídeos , Glioblastoma , Antineoplásicos/farmacologia , Apoptose , Arsênio/metabolismo , Arsenitos/farmacologia , Bufanolídeos/farmacologia , Caspase 8/metabolismo , Caspase 9/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos
6.
Polym J ; 54(6): 821-825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35311245

RESUMO

Liquid-crystalline (LC) water-treatment membranes obtained by in situ photopolymerization of ionic mesogenic monomers have been shown to efficiently remove viruses. In our previous works, bicontinuous cubic (Cubbi) and smectic (Sm) LC membranes prepared from ionic taper- and rod-shaped polymerizable mesogens, respectively, were used for this purpose. Here, we report the results of virus removal by columnar (Col) LC water-treatment membranes having ionic nanochannels obtained from ionic taper-shaped mesogens. These effects are compared with those obtained for Cubbi membranes. The effects of these Col and Cubbi LC ionic membranes on the removal of several viruses from their cocktail solution are also examined.

7.
Angew Chem Int Ed Engl ; 59(52): 23461-23465, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33073915

RESUMO

We demonstrate hydrogen-bonded structures of water in self-organized subnanoporous water treatment membranes obtained using synchrotron-based high-resolution soft X-ray emission spectroscopy. The ion selectivity of these water treatment membranes is usually understood by the size compatibility of nanochannels in the membrane with the Stokes radius of hydrated ions, or by electrostatic interaction between charges inside the nanochannels and such ions. However, based on a comparison between the hydrogen-bonded structures of water molecules in the nanochannels of the water treatment membrane and those surrounding the ions, we propose a definite contribution of structural consistency among the associated hydrogen-bonded water molecules to the ion selectivity. Our observation delivers a novel concept to the design of water treatment membranes where water molecules in the nanochannel can be regarded as a part of the material that controls the ion selectivity.

8.
ACS Omega ; 5(21): 12073-12080, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32548386

RESUMO

Ferulic acid derivative 012 (FAD012) is a ferulic acid (FA) derivative. The current study prepared a solid dispersion of FAD012 and γ-cyclodextrin (γCD) and ground it using a three-dimensional ball mill (3DGM) to prepare an inclusion complex. This study also assessed the physicochemical properties such as solubility of that complex. A Job's plot indicated that FAD012 and γCD formed an inclusion complex at a molar ratio of 1:1. Phase solubility diagrams revealed that FAD012 produced a BS diagram. According to PXRD, FAD012 produced a diffraction peak at 2θ = 7.0° and γCD produced a diffraction peak at 2θ = 9.1°. Those two peaks were not produced by the 3DGM, but new peaks (2θ = 7.3 and 16.5°) were evident. DSC patterns revealed an endothermic peak due to the melting of FAD012 at 190 °C, but no endothermic peaks were evident with the 3DGM. NIR spectra of the 3DGM indicated that the methyl group of FAD012 produced a higher peak and that the OH groups of γCD produced a higher peak. 1H-1H ROESY NMR spectra (D2O) revealed cross peaks for protons of the methyl group of FAD012 and a proton (H-3) in the cavity of γCD, so FAD012 presumably interacts with the wide opening of the γCD torus. A solubility test (25 °C) indicated that solubility improved about 5-fold for the 3DGM in comparison to the solubility of FAD012 alone (about 140 µg/mL). Based on these findings, an FAD012/γCD complex was formed by cogrinding, and its solubility improved. These observations are expected to expand the usefulness of cogrinding of FAD012 with γCD using a 3D ball mill.

9.
Eur J Cancer ; 135: 11-21, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32526634

RESUMO

BACKGROUND: Cetuximab has been shown to be clinically active when given in combination with irinotecan in patients with irinotecan-refractory metastatic colorectal cancer (mCRC). However, it has remained unclear whether panitumumab is effective when combined with irinotecan. We compared efficacies of both regimens in this randomised phase II study. PATIENTS AND METHODS: Patients with wild-type KRAS exon 2 mCRC previously treated with fluorouracil-, oxaliplatin- and irinotecan-based chemotherapies were randomised (1:1) to either panitumumab plus irinotecan (panitumumab arm) or cetuximab plus irinotecan (cetuximab arm). The primary end-point was progression-free survival (PFS). The planned sample size was 120, expecting a hazard ratio (HR) of 1.0 with non-inferiority margin of 1.3 (one-sided alpha error 0.2 and power 0.7). Major secondary end-points were overall survival (OS), response rate and safety. RESULTS: From December 2011 to September 2014, 121 patients were enrolled, and 61 and 59 patients were randomised to the panitumumab and cetuximab arms, respectively (1 patient excluded). Most patients (97%) had received prior chemotherapies containing bevacizumab. The median PFS was 5.42 months in the panitumumab arm and 4.27 months in the cetuximab arm (HR = 0.64, 95% confidence interval [CI] = 0.44-0.94, P < 0.001 for non-inferiority, P = 0.058 for superiority), and median OS was 14.85 and 11.53 months (HR = 0.66, 95% CI = 0.44-1.00, P = 0.050 for superiority), respectively. The incidence of grade 3 or 4 hypomagnesaemia was higher in the panitumumab arm than that in the cetuximab arm (17% vs. 7%). CONCLUSION: Panitumumab may be non-inferior to cetuximab in combination with irinotecan in survival of patients with irinotecan-refractory mCRC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Cetuximab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Irinotecano/administração & dosagem , Oxaliplatina/administração & dosagem , Panitumumabe/administração & dosagem , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab/efeitos adversos , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/efeitos adversos , Humanos , Irinotecano/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mutação , Oxaliplatina/efeitos adversos , Panitumumabe/efeitos adversos , Intervalo Livre de Progressão , Fatores de Tempo
10.
Spine Surg Relat Res ; 4(2): 130-134, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32405558

RESUMO

INTRODUCTION: Symptomatic postoperative hematoma after spine surgery is a rare but serious complication. The objective of this study was to investigate the incidence and clinical features of symptomatic postoperative hematoma after spine surgery. METHODS: We retrospectively identified 10,680 patients who underwent spine surgery between 2002 and 2012 in nine hospitals. We reviewed the incidence of postoperative hematoma and its clinical features, including time before onset, main symptoms, and neurological outcomes. RESULTS: The overall incidence of symptomatic postoperative hematoma after spine surgery was 0.4% (45/10,680). Postoperative hematoma was more frequent after thoracic spine surgery than after cervical or lumbar surgery. The onset of postoperative hematoma occurred at an average of 2.6 days (range 0-14 days) postoperatively. The chief symptoms caused by postoperative hematoma after spine surgery were tetra/paraplegia in 30 patients, hemiplegia in eight patients, intractable pain in five patients, and airway dysfunction in two patients. Surgical evacuation of the spinal epidural hematoma resulted in improvement of at least one grade in 35 patients, while four patients had complete motor paralysis even after evacuation surgery. CONCLUSIONS: We report the clinical details of 45 patients with postoperative hematoma after spine surgery. This information could assist surgeons to make a prompt diagnosis and perform early evacuation surgery for postoperative hematoma following spine surgery.

11.
Small ; 16(23): e2001721, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32363808

RESUMO

To obtain high quality of drinking water free from biocontaminants is especially important issue. A new strategy employing smectic liquid-crystalline ionic membranes exhibiting 2D structures of layered nanochannels for water treatment is proposed for efficient virus removal and sufficient water flux. The smectic A (SmA) liquid-crystalline membranes obtained by in situ polymerization of an ionic mesogenic monomer are examined for removal of three distinct viruses with small size: Qß bacteriophage, MS2 bacteriophage, and Aichi virus. The semi-bilayer structure of the SmA significantly obstructs the virus penetration with an average log reduction value of 7.3 log10 or the equivalent of reducing 18 million viruses down to 1. Furthermore, the layered nanochannels of the SmA liquid crystal allow efficient water permeation compared to other types of liquid-crystalline membrane consisting of nanopores.


Assuntos
Cristais Líquidos , Nanoestruturas , Vírus , Purificação da Água , Membranas Artificiais
12.
Gastric Cancer ; 23(4): 677-688, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32036492

RESUMO

BACKGROUND: Oral fluoropyrimidine plus cisplatin is often not tolerated by patients with severe peritoneal metastases of gastric cancer. Combination of 5-fluorouracil (5-FU), l-leucovorin (l-LV), and paclitaxel (FLTAX) has promising activity for such patients. We conducted a phase II/III study comparing FLTAX with 5-FU/l-LV. METHODS: Eligibility criteria included: unresectable or recurrent gastric adenocarcinoma; 20-75 years; performance status (PS) 0-2; peritoneal metastases + ; massive ascites and/or inadequate oral intake; no prior chemotherapy. Patients were randomly assigned to receive 5-FU/l-LV or FLTAX. The primary endpoint of phase III was overall survival: UMIN000010949. RESULTS: We enrolled 101 patients. Early deaths occurred in patients with PS 2 having massive ascites and inadequate oral intake simultaneously; the protocol was amended to exclude such patients. Median survival times were 6.1 and 7.3 months for the 5-FU/l-LV and the FLTAX arms, respectively (HR 0.792; 80% CI 0.596-1.053; one-sided p = 0.1445). FLTAX arm had longer progression-free survival (PFS) [1.9 vs 5.4 months (HR 0.64; 95% CI, 0.43-0.96; p = 0.029)]. Grade 3/4 adverse events such as leucopenia and anorexia were more frequently observed in the 5-FU/l-LV arm. In the 5-FU/l-LV arm, two deaths were treatment-related. In the 5-FU/l-LV and FLTAX arms, 12 and 3 deaths occurred within 30 days after the last protocol treatment, respectively. CONCLUSIONS: Chemotherapy was indicated for patients with severe peritoneal metastases excluding patients with PS 2 having massive ascites and inadequate oral intake simultaneously. FLTAX did not confer a significant survival benefit but may be preferred because of longer PFS and acceptable toxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/secundário , Idoso , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/secundário , Prognóstico , Neoplasias Gástricas/patologia , Taxa de Sobrevida
13.
Ann Surg Oncol ; 27(1): 284-292, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31535301

RESUMO

BACKGROUND: Gastric cancer (GC) patients with positive peritoneal lavage cytology (CY1) and/or localized peritoneum metastasis (P1a) are defined as stage IV in the 15th edition of the Japanese Classification of Gastric Cancer. In Japan, the most common treatment for patients with CY1 and/or P1a is gastrectomy followed by postoperative chemotherapy. PATIENTS AND METHODS: Subjects in this multi-institutional retrospective study were GC patients with CY1 and/or P1a who received surgical resection that leaves no macroscopically visible disease. Patients were selected from 34 institutions in Japan between 2007 and 2012. Selection criteria included adenocarcinoma, no distant metastasis except CY1 and P1a, and no prior treatment for GC before surgery. RESULTS: Among 824 patients registered, 506 were identified as eligible, with a background of P0CY1, P1aCY0, or P1aCY1 (72.5%, 16.0%, and 11.5% of subjects, respectively). Sixty-two patients had not received postoperative chemotherapy (no-Cx), whereas 444 patients had received postoperative chemotherapy: S-1 monotherapy (S-1; n = 267, 52.7%), cisplatin plus S-1 (CS; n = 114, 22.5%), and others (n = 63, 12.6%). Overall survival (OS) was 29.5, 24.7, 25.4 and 9.9 months in the S-1, CS, 'others', and no-Cx groups, respectively [CS vs. S-1: hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.89-1.50; p = 0.275]. In multivariate analysis, OS was similar between the S-1 and CS groups (CS vs. S-1: HR 1.19, 95% CI 0.92-1.55; p = 0.18). CONCLUSIONS: Postoperative chemotherapy after gastrectomy that leaves no macroscopically visible disease may have some survival benefits for GC patients with CY1 and/or P1a. In contrast, S-1 plus cisplatin seems to have no additional benefit over S-1 treatment alone.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Ácido Oxônico/administração & dosagem , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagem , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Gastrectomia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Cavidade Peritoneal/citologia , Lavagem Peritoneal , Período Pós-Operatório , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Adulto Jovem
14.
Rapid Commun Mass Spectrom ; 34(7): e8636, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31659809

RESUMO

RATIONALE: Ferulic acid (FA) is a standard matrix used for analyzing proteins. In this study, the ability of a halogenated FA to serve as an effective MALDI matrix was investigated. Various halogenated FAs were synthesized, and the characteristics and performance of each were compared with those of the standard matrices α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydrobenzoic acid (DHBA). METHODS: The abilities of 6-bromoferulic acid (6-BFA), ferulic acid (FA), and eight other halogenated FA derivatives to ionize eight synthetic peptides were examined. Absorption measurements, MM2 structure optimizations, and proton affinity (PA) calculations were also performed for 6-BFA and FA. The suitabilities of these compounds as matrices for matrix-assisted laser desorption/ionization (MALDI) for lipids, sugar chains, polymers, cyanocobalamin, synthetic peptides, and tryptic peptides originating from two types of serum proteins were also tested. RESULTS: The 6-position of FA was found to be the best site for introducing a bromine because the generated compound allowed facile detection of cyanocobalamin and several peptides. 6-BFA exhibited good sensitivity for large peptides (3-5 kDa) and peptides containing acidic amino acids or proline. 6-BFA was also shown to be a suitable matrix for tandem mass spectrometry (MS/MS) analysis when using MALDI time-of-flight (TOF) mass spectrometry (MS) with a quadrupole ion trap (QIT) system. CONCLUSIONS: The properties of 6-BFA as a MALDI matrix differed from those of DHBA and CHCA. 6-BFA appears to be a useful matrix for de novo sequencing using MALDI-QIT-TOF-MS.


Assuntos
Ácidos Cumáricos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Proteínas Sanguíneas/análise , Halogenação , Humanos , Lipídeos/análise , Peptídeos/análise , Espectrometria de Massas em Tandem/métodos , Vitamina B 12/análise
15.
Jpn J Clin Oncol ; 49(11): 1055-1060, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31411696

RESUMO

A randomized phase III trial commenced in Japan in February 2018. Definitive chemoradiotherapy (CRT) with cisplatin plus 5-fluorouracil is the current standard treatment for locally advanced unresectable esophageal carcinoma. The purpose of this study is to confirm the superiority of induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) followed by conversion surgery or definitive CRT over definitive CRT alone for overall survival (OS) in patients with locally advanced unresectable squamous-cell carcinoma of thoracic esophagus. A total of 230 patients will be accrued from 47 Japanese institutions over 4.5 years. The primary endpoint is OS, and the secondary endpoints are progression-free survival, complete response rate of CRT, response rate of DCF, adverse events of DCF and CRT, late adverse events and surgical complications. This trial has been registered at the Japan Registry of Clinical Trials as jRCTs031180181.


Assuntos
Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada/métodos , Feminino , Humanos , Quimioterapia de Indução/métodos , Japão , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão
16.
Lancet Gastroenterol Hepatol ; 4(7): 501-510, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31101534

RESUMO

BACKGROUND: We investigated the superiority of docetaxel plus cisplatin and S-1 compared with cisplatin and S-1 in chemotherapy-naive patients with advanced gastric cancer. METHODS: In this open-label, phase 3, randomised controlled trial, patients were recruited from 56 hospitals in Japan. We enrolled individuals aged 20-75 years who had unresectable or recurrent gastric cancer, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, had received no previous chemotherapy (except adjuvant chemotherapy completed 24 weeks before reccurence), radiotherapy, or hormonal therapy, could take drugs orally, and had adequate organ function. Patients were randomly assigned (1:1) to receive docetaxel plus cisplatin and S-1 (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1 intravenously, and S-1 40-60 mg twice a day orally for 2 weeks, every 4 weeks) or cisplatin and S-1 (cisplatin 60 mg/m2 intravenously on day 8, and S-1 40-60 mg orally twice a day for 3 weeks, every 5 weeks). Randomisation was done centrally with the minimisation method, with a random component balancing for institution, ECOG performance status (0 vs 1), disease status at enrolment (unresectable vs recurrent), measurable lesion (yes vs no), number of metastatic sites (0-1 vs ≥2), and histological type (differentiated vs undifferentiated). Neither investigators or patients were masked to the study treatment. The primary endpoint was overall survival in the intention-to-treat population. The study is registered with UMIN-CTR, number UMIN000007652. FINDINGS: Between April 3, 2012, and March 18, 2016, 741 patients were randomly assigned to receive docetaxel plus cisplatin and S-1 (n=370) or cisplatin and S-1 (n=371). Median overall survival was 14·2 months (95% CI 12·9-15·9) in the docetaxel plus cisplatin and S-1 group and 15·3 months (14·2-16·2) in the cisplatin and S-1 group (hazard ratio [HR] 0·99 [95% CI 0·85-1·16]; one-sided stratified log-rank p=0·47). The most common grade 3 or worse adverse events were neutropenia (209 [59%] of 357 patients in the docetaxel plus cisplatin and S-1 group vs 117 [32%] of 365 patients in the cisplatin and S-1 group), leukopenia (120 [34%] vs 60 [16%]), and anorexia (94 [26%] vs 81 [22%]). The deaths of one patient in the cisplatin and S-1 group and in three patients in the docetaxel plus cisplatin and S-1 group were deemed treatment-related. INTERPRETATION: The addition of docetaxel to cisplatin and S-1 did not improve overall survival in chemotherapy-naive Japanese patients with advanced gastric cancer. Therefore, cisplatin and S-1 remains the standard first-line chemotherapy. FUNDING: Ministry of Health, Labour and Welfare and Japan Agency for Medical Research and Development.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Neoplasias Gástricas/mortalidade , Resultado do Tratamento , Adulto Jovem
17.
ACS Macro Lett ; 8(1): 24-30, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35619406

RESUMO

Here we report columnar liquid-crystalline (LC) nanostructured membranes that highly remove viruses and show sufficient water permeation. These membranes were prepared by employing two-component liquid crystals that exhibit tetragonal columnar phases. The membranes exhibited virus rejection values of >99.99% (log10 reduction value (LRV) > 4) and water flux ranging from 19 to 61 L m-2 h-1 (operation pressure: 0.3 MPa). These membranes were fabricated by photopolymerization of a fan-shaped diol molecule and imidazolium ionic liquid mixture, followed by subsequent removal of the ionic liquid. The rejection values and water flux depend on the fraction of ionic liquid. These results show new design strategies of materials for the water treatment nanostructured membranes that remove pathogens and contaminants.

18.
ACS Macro Lett ; 8(10): 1303-1308, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35651161

RESUMO

Here, we describe a strategy to obtain nanoporous liquid-crystalline (LC) membranes by incorporating a photocleavable ortho-nitrobenzyl group in polymerizable columnar liquid crystals. Two derivatives were synthesized with propylene and nonylene spacers, respectively, between the ionic and the photocleavable moieties to introduce various size nanopores after photocleavage. The membranes were prepared by photopolymerization in the LC states, followed by photocleavage and washing with methanol. The resulting membranes show a virus rejection of 99.99%. Although the rejection value remained almost the same for the two membranes, water flux increased with increasing the length of the alkyl spacers. These membranes were found to be almost free from pinhole defects. The present study offers a new methodology for the development of nanoporous membranes with organized nanostructures for separation technologies.

19.
Angew Chem Int Ed Engl ; 57(16): 4355-4371, 2018 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-29534321

RESUMO

Since the discovery of the liquid-crystalline state in 1888, liquid crystal science has made great advances through fusion with various technologies and disciplines. Recently, new molecular design strategies and new self-assembled structures have been developed as a result of the progress made in synthetic procedures and characterization techniques. Since these liquid crystals exhibit new functions and properties derived from their nanostructures and alignment, a variety of new functions for liquid crystals, such as transport for energy applications, separation for environmental applications, chromism, sensing, electrooptical effects, actuation, and templating have been proposed. This Review presents recent advances of liquid crystals that should contribute to the next generation of materials.

20.
J Orthop Sci ; 23(3): 464-469, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29452792

RESUMO

BACKGROUND: Although a valve-like mechanism has been proposed for expansion of spinal extradural arachnoid cysts (SEACs), the detailed mechanism remains unclear. Moreover, closure of the communication site is essential during surgery, but the method to identify the communication site remains unclear. The aim of this study was to determine the detailed mechanism of expanding SEACs through retrospective analysis of SEAC cases undergoing surgery and to elucidate the characteristics of the communication sites. METHODS: The authors retrospectively evaluated 12 patients with SEACs who underwent surgery between 2000 and 2014 and analyzed their perioperative findings. RESULTS: Dural defects were detected in 11 out of 12 patients, and a valve-like mechanism was observed in 7 patients, wherein a nerve root fiber moved back and forth through the dural defect along with the flow of cerebrospinal fluid (CSF) between the intradural space and the extradural arachnoid cysts. The dural defect was located at the thoracolumbar junction in 7 patients, below the distal end of the bridging ossification in 2, at the level of vertebral wedge deformity in 2, and at the level of disc herniation in 1. CONCLUSIONS: A valve-like mechanism was observed in 7 of the 12 patients, which suggests that it could serve as a mechanism of SEAC formation. The communication sites were variously located at the end of ossification in patients with diffuse idiopathic skeletal hyperostosis (DISH), wedge deformity of the vertebral body, or disc herniation, indicating the contribution of mechanical stress to SEAC formation.


Assuntos
Cistos Aracnóideos/diagnóstico , Cistos Aracnóideos/etiologia , Dura-Máter/diagnóstico por imagem , Dura-Máter/patologia , Raízes Nervosas Espinhais/diagnóstico por imagem , Raízes Nervosas Espinhais/patologia , Adulto , Idoso , Cistos Aracnóideos/cirurgia , Feminino , Humanos , Vértebras Lombares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vértebras Torácicas , Tomografia Computadorizada por Raios X
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