Lipid-membrane-incorporated arylboronate esters as agents for boron neutron capture therapy

Arylboronate esters bearing methyl groups in both of their ortho positions were stably incorporated into lipid membranes at high concentrations without undergoing hydrolysis to the corresponding boronic acids. This method could be used in combination with previous methods to increase the maximum ratio of boron atoms in liposomal boron carriers.This work was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research (B) (Grant No. JP16H04133) and a Grant-in-Aid for Challenging Exploratory Research (Grant No. JP16K13982)

Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer

Schematic diagrams of the signal cascade of EGF-induced DPD expression of EGFR-mutated type cells. TF, transcription factor; Mit A, mithramycin A. (JPG 130 kb

Formation of β‐(1,3‐1,6)‐D‐glucan‐complexed [70]fullerene and its photodynamic activity towards macrophages

[70]Fullerene was dissolved in water by the complexation with β‐1,3‐glucan using a mechanochemical high‐speed vibration milling apparatus. The photodynamic activity of β‐1,3 glucan‐complexed C70 was highly dependent on the expression level of dectin‐1 on the cell surfaces of macrophages. The photodynamic activity increased as a result of a synergistic effect between β‐1,3‐glucan‐complexed 1’‐acetoxychavicol acetate and the C70 complex.This work was supported by JSPS KAKENHI Grant‐in‐Aid for Scientific Research (B) (Grant No. JP16H04133), Grant‐in‐Aid for Scientific Research (C) (Grant No. 26350528) and Grant‐in‐Aid for Challenging Exploratory Research (Grant No. JP16K13982)

An experience of hepatopancreatoduodenectomy in patients with hepatobiliary malignancies

BACKGROUND/AIMS: In the advanced stage of hepatobiliary malignancies, concurrent hepatopancreatoduodenectomy (HPD) is necessary to accomplish curative resection, even though high rates of morbidity and mortality still remain. METHODOLOGY: We examined the surgical records and outcome in 11 patients undergoing HPD. RESULTS: In 11 patients, diseases included bile duct carcinomas in 7 patients, gallbladder carcinomas in 3, and ampullar carcinoma in one. Hemi-hepatectomy with resection of the caudate lobe was performed in 8 patients and resection of segment 4 and 5 of the liver in two. Pancreatoduodenectomy (PD) was performed in 3 patients and pylorus-preserving PD in 8. Curative resection was accomplished in 8 patients. Two patients underwent adjuvant photodynamic therapy because of a cancer-positive margin. Morbidity rate was 36% but no hospital deaths were reported. The tumor recurrence rate was 73% and 8 patients died of cancer. Patient prognosis of gallbladder cancers (12 +/- 1 months) tended to be shorter than in patients with bile duct cancers (19 +/- 11 months) (p=0.15). Three patients with bile duct cancers survived without tumor relapse over 12 months. CONCLUSIONS: Complete surgical resection (R0) by HPD could be safely performed for diseases of the hepatobiliary malignancies, which achieved longer survival in some patients

High Expression of Dihydropyrimidine Dehydrogenase in Lung Adenocarcinoma is Associated With Mutations in Epidermal Growth Factor Receptor: Implications for the Treatment of Non?Small-Cell Lung Cancer Using 5-Fluorouracil

BackgroundIt has been shown that 5-fluorouracil (5-FU) sensitivity in patients with non?small-cell lung cancer (NSCLC) is associated with epidermal growth factor receptor (EGFR) mutation status. However, the relationship between dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, and EGFR mutation status is unknown. Here, we focus on clinicopathologic factors and in vitro correlations between DPD expression and EGFR mutation status.Patients and MethodsEGFR mutations and messenger RNA (mRNA) levels of DPD and thymidylate synthase (TS) were analyzed in 47 resected NSCLC tumors by laser-capture microdissection. In addition, relationships between EGFR mutation status and the immunohistochemical expression of DPD and TS in 49 patients with primary NSCLC who were treated with a 5-FU derivative of S-1 postoperatively were examined. Correlations among clinicopathologic factors were evaluated. The effect of epidermal growth factor on DPD expression was also investigated in vitro in various cell lines.ResultsAdenocarcinoma in situ showed significantly higher DPD mRNA levels and more EGFR mutation frequency than other histological types (P < .05). DPD immunopositive cases were more frequently observed in adenocarcinoma, in females, and in nonsmokers. DPD immunopositive cases were correlated with EGFR mutation status (P < .003). The prognoses of wild-type EGFR and mutated EGFR populations were similarly favorable with postoperative S-1 treatment, which overcomes the problem of 5-FU degradation in mutated EGFR. In vitro, EGFR-mutated cell lines showed high DPD mRNA and protein expression.ConclusionHigh DPD expression was shown to be correlated with EGFR mutation in adenocarcinoma cells and tissues. Clinicians should take this finding into consideration when using 5-FU to treat patients with NSCLC

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

Realization of high Ti plasmas and confinement characteristics of ITB plasmas in the LHD deuterium experiments

The deuterium (D) operation was initiated in the LHD in 2017. In the first campaign of the D experiments, we successfully extended the high temperature regime in the LHD. The new record of the ion temperature (Ti) of 10 keV associated with the ion internal transport barrier (ITB) was achieved due to several operational optimization. The thermal confinement characteristics of ITB plasmas were compared between hydrogen and D discharges. The effective ion thermal diffusivity of the ion-ITB plasmas was found to be smaller in the D discharges than that in the H discharges. The profiles of the Ti, the electron density, and the impurity of the high Ti plasmas strongly depended on the magnetic configuration and these profiles tended to peaked in the inward-shifted configuration. It was also found that the electron thermal confinement of the electron-ITB plasmas was clearly improved in the deuterium case. The GKV simulation showed the linear growth rate of TEM/ITG reduced in the plasmas with D both for the ion ITB and the electron ITB plasmas and qualitatively agreed with the tendency of the change in the thermal diffusivity obtained from the power balance analysis

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection