An Initial Case Report of a Laparoscopic Spleen-Preserving Distal Pancreatectomy for a Patent with a Pancreatic Metastasis of Malignant Melanoma

Article信州医学雑誌 63(1):19-24(2015)journal articl

Gemcitabine sensitivity-related mRNA expression in endoscopic ultrasound-guided fine-needle aspiration biopsy of unresectable pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine a predictive indicator of gemcitabine (GEM) efficacy in unresectable pancreatic cancer using tissue obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA).</p> <p>Methods</p> <p>mRNAs extracted from 35 pancreatic tubular adenocarcinoma tissues obtained by EUS-FNA before GEM-treatment were studied. mRNAs were amplified and applied to a Focused DNA Array, which was restricted to well-known genes, including GEM sensitivity-related genes, deoxycytidine kinase (dCK), human equilibrative nucleoside transporter 1 (hENT1), hENT2, dCMP deaminase, cytidine deaminase, 5'-nucleotidase, ribonucleotide reductase 1 (RRM1) and RRM2. mRNA levels were classified into high and low expression based on a cut-off value defined as the average expression of 35 samples. These 35 patients were divided into the following two groups. Patients with partial response and those with stable disease whose tumor markers decreased by 50% or more were classified as the effective group. The rest of patients were classified as the non-effective group. The relationship between GEM efficacy and mRNA expression was then examined by chi-squared test.</p> <p>Results</p> <p>Among these GEM sensitivity-related genes, dCK alone showed a significant correlation with GEM efficacy. Eight of 12 patients in the effective group had high dCK expression, whereas 16 of 23 patients in non-effective group had low dCK expressions (<it>P </it>= 0.0398).</p> <p>Conclusion</p> <p>dCK mRNA expression is a candidate indicator for GEM efficacy in unresectable pancreatic cancer. Quantitative mRNA measurements of dCK using EUS-FNA samples are necessary for definitive conclusions.</p

N-Acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 21

ダウン症患者さん由来の神経細胞からのアミロイドβ分泌は抗酸化剤で抑止される. 京都大学プレスリリース. 2021-08-31.Stopping dementia in Down syndrome patients. 京都大学プレスリリース. 2021-08-31.Down syndrome (DS) is caused by the trisomy of chromosome 21. Among the many disabilities found in individuals with DS is an increased risk of early-onset Alzheimer's disease (AD). Although higher oxidative stress and an upregulation of amyloid β (Aβ) peptides from an extra copy of the APP gene are attributed to the AD susceptibility, the relationship between the two factors is unclear. To address this issue, we established an in vitro cellular model using neurons differentiated from DS patient-derived induced pluripotent stem cells (iPSCs) and isogenic euploid iPSCs. Neurons differentiated from DS patient-derived iPSCs secreted more Aβ compared to those differentiated from the euploid iPSCs. Treatment of the neurons with an antioxidant, N-acetylcysteine, significantly suppressed the Aβ secretion. These findings suggest that oxidative stress has an important role in controlling the Aβ level in neurons differentiated from DS patient-derived iPSCs and that N-acetylcysteine can be a potential therapeutic option to ameliorate the Aβ secretion

Free-carrier dynamics and band tails in Cu[2] ZnSn (S[x]Se[1−x] )[4] : Evaluation of factors determining solar cell efficiency

We investigated the composition-dependent photocarrier dynamics in Cu[2] ZnSn(S[x]Se[1−x])[4] (CZTSSe) single crystals using various types of steady-state and time-resolved optical spectroscopy. Photoluminescence spectroscopy shows that the band-tail states formed below the band edge decrease monotonically with increasing Se content. THz time-resolved spectroscopy clarifies that an increase in the Se content leads to a shorter lifetime of the free photocarriers. A trade-off between the composition-dependent band-tail density and the free-carrier lifetime occurs in CZTSSe single crystals. Our experimental results provide insights into the physics behind the low and composition-dependent conversion efficiency of CZTSSe-based solar cells

Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study

Objective To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use.Design A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study.Results The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference –2.2%,95% CI –6.2% to 1.8%, p<0.001; –2.1%,95% CI –6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified.Conclusion The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg)

Clinical Guides for aHUS

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. In 2013, we developed diagnostic criteria to enable early diagnosis and timely initiation of appropriate treatment for aHUS. Recent clinical and molecular findings have resulted in several proposed classifications and definitions of thrombotic microangiopathy and aHUS. Based on recent advances in this field and the emerging international consensus to exclude secondary TMAs from the definition of aHUS, we have redefined aHUS and proposed diagnostic algorithms, differential diagnosis, and therapeutic strategies for aHUS

The PI3K-Akt Pathway in SN-38-Induced Apoptosis in Human Gastric Cancer Cell Lines

SN-38, an active metabolite of a topoisomerase I inhibitor, CPT-11, exhibits a cytotoxic effect by inducing apoptosis in cancer cells. Phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling is known to protect a variety of cells from apoptosis. The relationship between resistance to SN-38-induced apoptosis and the PI3K-Akt pathway in human gastric cancer cells is unknown. Here, we did an investigation using two gastric cancer cell lines, MKN1 and MKN45. Cell viability was determined by sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) assay. Apoptosis was confirmed by fluorescence microscopy using Hoechst 33342 staining. Expression levels of phospho-Akt (pAkt) were determined by Western blotting. After being treated with SN-38, the populations of sub-G1 cells were induced by flow cytometry in 36.8% of MKN45 cells more frequently than in 13.5% of MKN1 cells. SN-38 inhibited the expression of pAkt dose-dependently in MKN45 cells, but not in MKN1 cells. In MKN1 cells, an additional pretreatment with the PI3K inhibitor, LY294002, led to the inhibition of pAkt expression and induced apoptosis. The results suggested that SN-38 induces apoptosis by decreasing PI3K-Akt survival signaling, the anti-apoptotic signals, in human gastric cancer cells. Akt inhibitor might be a useful anti-tumor agent in combination with CPT-11

Etude système de diodes lasers à verrouillage de modes pour la radio-sur-fibre en bande millimétrique

Ce travail de thèse s inscrit dans la recherche des solutions économiquementviables pour des réseaux personnels à hauts débits (plusieurs Gbps à plusieursdizaines de Gbps) opérationnels en bande millimétrique autour de 60 GHz. Aucas où ces réseaux servent un nombre élevé d utilisateurs, ils comprendront unemultitude d antennes afin d assurer l accès sans fil rapide. Afin de réduire aumaximum le coût d un module d antenne, les réseaux doivent fournir un signalanalogue à des porteuses millimetriques. Une solution prometteuse pour les systèmesde distribution qui correspond à ces besoins sont des structures à fibreoptique, laquelle permet une transmission à faibles pertes et à haute bande passante.On parle de l approche "radio-sur-fibre" (en anglais, radio-over-fiber). Laproblématique est de pouvoir générer et moduler un signal aux fréquences millimétriqueslors de la transmission optique - et ce avec des composant bas coûts.La technique utilisée dans le cadre de cette thèse est l emploi des diodes laser àverrouillage de modes. Ces derniers vont pouvoir générer des hautes fréquencestout en ne nécessitant qu une alimentation continue, et ils peuvent être modulésde manière directe ou externe. Les lasers à semi-conducteurs employés ici sontd une génération encore à l état d étude puisqu il s agit des lasers à boites (ouîlots) quantiques. Ces lasers ont montrés de très bonnes capacités à générer dessignaux électriques aux fréquences autour de 60 GHz, bien qu ayant encore, pourl instant, à une stabilité de fréquence (ou de phase) limitée. Dans le cadre des systèmesde communication opto/micro-ondes, peu de travaux approfondis ont étémenés sur ces structures.Au cours de cette thèse, plusieurs études ont été effectuées. La première portesur les propriétés générales d un système construit à partir de ce type de laser(puissances disponibles, figure de bruit, linéarité etc.). Une deuxième étude aété consacrée aux effets de la propagation des signaux dans les systèmes baséssur les lasers à verrouillage de modes, notamment de la dispersion chromatiquelaquelle a un effet considérable sur les distances de transmission. Les deux étudesmettent en avant l importance d une limitation du nombre de modes générés parla diode laser afin d optimiser non seulement le gain du lien et la puissance RFrécupérée, mais aussi la figure de bruit du système. Lors d une troisième étude, lastabilité en fréquence/phase s est révélée critique, car le bruit de fréquence/phaselimite la qualité de la transmission en introduisant un plancher d erreur mêmepour des rapports signal-a-bruit très élevés. Des différentes générations de lasersà boites (îlots) quantiques et à verrouillage de modes ont été testées. Le problèmedu bruit de fréquence et de phase persiste et ne peut pas être résolu en utilisantles techniques classiques comme les boucles à verrouillage de phase conventionnelles.Une solution pour ce problème a été développée pour les systèmes detransmission; elle permet simultanément un ajustement de fréquence supérieure(précision de quelques Hz à quelques kHz) à celle donnée par le processus de fabricationdes diodes lasers (précision de quelques GHz), ainsi qu une stabilisationde fréquence et de phase.This dissertation is related to the search for an economically sustainable solutionfor high data rate (several Gbps to several tens of Gbps) personal area networksoperating in the millimeter-wave region around 60 GHz. If such networks supplya large number of users, they need to encompass a multitude of antenna pointsin order to assure wireless access to the network. With the aim of reducing thecost of an antenna module, the networks should at best provide quasi "readyto-radiate" signals to the modules, i.e. at millimeter-wave carrier frequencies.Thanks to their low transmission loss and their high bandwidth, optical fiber distributionarchitectures represent a promising solution. The technique is referredto as the so-called "radio-over-fiber" approach whereby the analog radio signalwill be transported to the access point by an optical wave. The challenge herebyis the generation and modulation of an optical signal by a millimeter-wave radiosignal using preferably cost-efficient system components. The technique proposedherein is based on the use of mode-locked laser diodes which can generatesignals at very high frequencies under the condition of continuous current supply.Mode-locked laser diodes can be modulated both directly and externally. Thediodes employed in this work are based on so-called quantum dots (or quantumdashes); these are material structures which are themselves still subject to intensivephysical research. Signals at millimeter-wave frequencies (around 60 GHz)can easily be generated by such lasers. However, their frequency and phase stabilityis as yet limited. In the context of radio-over-fiber communication systems,these structures have not yet been studied in detail.In the course of this dissertation, several aspects are considered. A first systemstudy treats the basic properties of a system built from this type of laser source(available signal power, system noise figure, linearity etc.). A second study isdevoted to an investigation of propagation effects like dispersion, which considerablyinfluence the attainable transmission distances. An essential result of bothstudies is the importance of limiting the laser spectrum to a small number of lasermodes for an optimization of link gain, generated RF power, and system noisefigure. A third study deals with the limited frequency and phase stability whichturn out to be critical factors for transmission quality. The study of several generationsof quantum dot/dash lasers has revealed that the problems of frequencyand phase noise persist and cannot be solved using classical techniques involvinge.g. conventional phase-locked loops. In this dissertation, a solution is presentedwhich not only allows a more precise adjustment of the laser frequency (precisionin the order of Hz to kHz) than that given by the manufacturing process of thelaser (precision in the order of GHz), but also enables a stabilization of frequencyand phase.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Botrytis cinerea tolerates phytoalexins produced by Solanaceae and Fabaceae plants through an efflux transporter BcatrB and metabolizing enzymes

Botrytis cinerea, a plant pathogenic fungus with a wide host range, has reduced sensitivity to fungicides as well as phytoalexins, threatening cultivation of economically important fruits and vegetable crops worldwide. B. cinerea tolerates a wide array of phytoalexins, through efflux and/or enzymatic detoxification. Previously, we provided evidence that a distinctive set of genes were induced in B. cinerea when treated with different phytoalexins such as rishitin (produced by tomato and potato), capsidiol (tobacco and bell pepper) and resveratrol (grape and blueberry). In this study, we focused on the functional analyses of B. cinerea genes implicated in rishitin tolerance. LC/MS profiling revealed that B. cinerea can metabolize/detoxify rishitin into at least 4 oxidized forms. Heterologous expression of Bcin08g04910 and Bcin16g01490, two B. cinerea oxidoreductases upregulated by rishitin, in a plant symbiotic fungus Epichloë festucae revealed that these rishitin-induced enzymes are involved in the oxidation of rishitin. Expression of BcatrB, encoding an exporter of structurally unrelated phytoalexins and fungicides, was significantly upregulated by rishitin but not by capsidiol and was thus expected to be involved in the rishitin tolerance. Conidia of BcatrB KO (ΔbcatrB) showed enhanced sensitivity to rishitin, but not to capsidiol, despite their structural similarity. ΔbcatrB showed reduced virulence on tomato, but maintained full virulence on bell pepper, indicating that B. cinerea activates BcatrB by recognizing appropriate phytoalexins to utilize it in tolerance. Surveying 26 plant species across 13 families revealed that the BcatrB promoter is mainly activated during the infection of B. cinerea in plants belonging to the Solanaceae, Fabaceae and Brassicaceae. The BcatrB promoter was also activated by in vitro treatments of phytoalexins produced by members of these plant families, namely rishitin (Solanaceae), medicarpin and glyceollin (Fabaceae), as well as camalexin and brassinin (Brassicaceae). Consistently, ΔbcatrB showed reduced virulence on red clover, which produces medicarpin. These results suggest that B. cinerea distinguishes phytoalexins and induces differential expression of appropriate genes during the infection. Likewise, BcatrB plays a critical role in the strategy employed by B. cinerea to bypass the plant innate immune responses in a wide variety of important crops belonging to the Solanaceae, Brassicaceae and Fabaceae