LAMC2 promotes gemcitabine resistance in PDAC

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis. Gemcitabine remains an effective option for the majority of PDAC patients. Unfortunately, currently no reliable prognostic and predictive biomarkers of therapeutic response are available for the patients with PDAC. Laminin γ2 (LAMC2) is overexpressed in several cancers, and its high expression facilitates cancer development and chemoresistance. However, its functional role in PDAC remains unclear, and a better understanding of this will likely help improve the prognosis of PDAC patients. This study aimed to elucidate the clinical and biological role of LAMC2 in PDAC. We first analyzed the expression levels of LAMC2 by real-time reverse transcription PCR in a cohort of 114 PDAC patients. Interestingly, higher expression of LAMC2 significantly correlated with poor survival in PDAC cohort. In addition, elevated LAMC2 expression served as a potential prognostic marker for survival. Subsequently, functional characterization for the role of LAMC2 in PDAC was performed by small interfering RNA (siRNA) knockdown in pancreatic cancer (PC) cell lines. Interestingly, inhibition of LAMC2 in PC cells enhanced the gemcitabine sensitivity and induction of apoptosis. Moreover, it inhibited colony formation ability, migration, and invasion potential. Furthermore, LAMC2 regulated the expression of epithelial-mesenchymal transition (EMT) phenotype. In addition, LAMC2 significantly correlated with genes associated with the expression of ATP-binding cassette (ABC) transporters in PC cells and PDAC patients. In conclusion, these results suggest that LAMC2 regulates gemcitabine sensitivity through EMT and ABC transporters in PDAC and may be a novel therapeutic target in PDAC patients

Coagulation mechanism of salt solution-extracted active component in Moringa oleifera seeds

This study focuses on the coagulation mechanism by the purified coagulant solution (MOC-SC-PC) with the coagulation active component extracted from M. oleifera seeds using salt solution. The addition of MOC-SC-PC into tap water formed insoluble matters. The formation was responsible for kaolin coagulation. On the other hand, insoluble matters were not formed when the MOC-SC-PC was added into distilled water. The formation was affected by Ca2+ or other bivalent cations which may connect each molecule of the coagulation active component in MOC-SC-PC and form netlike structure. The coagulation mechanism of MOC-SC-PC seemed to be an enmeshment by the insoluble matters with netlike structure. In case of Ca2+ ion (bivalent cations), at least 0.2mM was necessary for coagulation at 0.3 mg-C l-1 dose of MOC-SC-PC. Other coagulation mechanisms like compression of double layer, interparticle bridging or charge neutralization were not responsible for the coagulation by MOC-SC-PC

Improvement of extraction method of coagulation active components from Moringa oleifera seed

A new method for the extraction of the active coagulation component from Moringa oleifera seeds was developed and compared with the ordinary water extraction method (MOC–DW). In the new method, 1.0 mol l-1 solution of sodium chloride (MOC–SC) and other salts were used for extraction of the active coagulation component. Batch coagulation experiments were conducted using 500 ml of low turbid water (50 NTU). Coagulation efficiencies were evaluated based on the dosage required to remove kaolinite turbidity in water. MOC–SC showed better coagulation activity with dosages 7.4 times lower than that using MOC–DW for the removal of kaolinite turbidity. MOC–SC could effectively coagulate more than 950f the 50 NTU initial kaolin turbidity using only 4 ml l-1, while 32 ml l-1 of MOC–DW could only remove about 781023440400f the same kaolin turbidity. The improvement of coagulation efficiency by NaCl is apparently due to the salting-in mechanism in proteins wherein a salt increases protein–protein dissociations, leading to increasing protein solubility as the salt ionic strength increases. There was no difference in the coagulation efficiency observed for extracts using any of four 1:1 salts (NaCl, KNO3, KCl and NaNO3) in our study. Purification and isolation of the active component confirmed that the active component of MOC–SC was mainly protein

Chemical Stabilization of Bottom Ash from Municipal Solid Waste Incineration and Prediction of DOC Leaching in Landfill Sites

It is well known that it takes long time to stabilize landfill and meet the standard for leachate after landfilling is stopped. Moreover, the time required to meet the standard is not predicted. In this research, the rapid small-scale column test (RSSCT) was applied and was found to predict the dissolved organic carbon (DOC) leaching from municipal solid waste incineration bottom ash in a simulated landfill site. Acid washing with hydrochloric acid remarkably reduced the DOC leaching from bottom ash. According to the RSCCT, it was estimated that the acid washing would reduce the time for DOC stabilization of bottom ash by about 80% in a simulated landfill situation.It is well known that it takes long time to stabilize landfill and meet the standard for leachate after landfilling is stopped. Moreover, the time required to meet the standard is not predicted. In this research, the rapid small-scale column test (RSSCT) was applied and was found to predict the dissolved organic carbon (DOC) leaching from municipal solid waste incineration bottom ash in a simulated landfill site. Acid washing with hydrochloric acid remarkably reduced the DOC leaching from bottom ash. According to the RSCCT, it was estimated that the acid washing would reduce the time for DOC stabilization of bottom ash by about 80% in a simulated landfill situation

Isolation and characterization of coagulant extracted from moringa oleifera seed by salt solution

It is known that M. oleifera contains a natural coagulant in the seeds. In our previous research, the method using salt water to extract the active coagulation component from M. oleifera seeds was developed and compared with the conventional method using water. In this research, the active coagulation component was purified from a NaCl solution crude extract of Moringa oleifera seeds. The active component was isolated and purified from the crude extract through a sequence of steps that included salting-out by dialysis, removal of lipids and carbohydrates by homogenization with acetone, and anion exchange. Specific coagulation activity of the active material increased up to 34 times more than the crude extract after the ion exchange. The active component was not the same as that of water extract. The molecular weight was about 3000 Da. The Lowry method and the phenol-sulfuric acid method indicated that the active component was neither protein nor polysaccharide. The optimum pH of the purified active component for coagulation of turbidity was pH 8 and above. Different from the conventional water extracts, the active component can be used for waters with low turbidity without increase in the dissolved organic carbon concentration

ポリシリカ鉄凝集剤を用いた凝集沈澱-急速ろ過処理の特性

本研究では水道用湖沼原水を対象にした一年間のパイロットプラントを用いた実証試験で、ポリシリカ鉄凝集剤(PSI)の凝集沈澱処理能力をポリ塩化アルミニウム(PAC)および塩化鉄と比較、評価した。PSIの濁度除去能は同じ鉄系凝集剤である塩化鉄と比べて水温の影響を受けにくく、水質変動に対してもPACと同様に安定した処理能力を示した。PSIの藻類除去能はPAC、塩化鉄より高いと考えられた。これはPSIが鉄系凝集剤であることに起因していることと、重合ケイ酸の効果により低水温期でも塩化鉄のように処理能力が悪化することが無かった為と考えられた。ろ過水の残留濁度および全藻類数はPSI、塩化鉄、PACの3つの凝集剤による違いはほとんどなかったが、PSIを使用した場合にはアンスラサイト層で特異的な損失の増加が起こり、PACや塩化鉄を使用した場合に比べてろ過塔の総損失水頭が高くなった。この損失の増加の原因としては、凝集沈殿処理水に残留したPSI由来の溶存の重合ケイ酸が、アンスラサイト表面に吸着して蓄積することにより、アンスラサイト層の空隙を閉塞することが考えられた。The objective of this study is to evaluate polysilicate-iron (PSI) coagulant in comparison with polyaluminum chloride (PAC) and ferric chloride coagulants on turbidity and algae removal. The evaluation was carried out using a pilot scale plant for a lake water in a year. Turbidity removal by PSI was not affected by water temperature, whereas that by ferric chloride deteriorated in winter. PSI showed higher removal efficiency for algae than PAC in all seasons and ferric chloride in winter. This higher removal efficiency by PSI might be explained by the fact that PSI was a ferric coagulant and contained polysilicate. The water quality of filtrated water with rapid filtration, was almost the same. The total head loss of rapid filtration in PSI was developed quicker than that in PAC and ferric chloride due to high head loss in the anthracite layer. The adsorption and accumulation of dissolved polysilicate remaining from the water coagulated by PSI onto the anthracite would cause the high head loss development

ダパグリフロジン投与における肥満２型糖尿病患者の治療満足度への影響：a patient reported outcome study (PRO study).

Background: The benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents. Methods: This multicenter, open-label, single-arm observational study included patients with type 2 diabetes mellitus administering dapagliflozin 5 or 10 mg per day for 14 weeks. Changes in treatment satisfaction were evaluated using a new version of the Oral Hypoglycemic Agent-Questionnaire (OHA-Q ver. 2) consisting of 23 items. Correlation between treatment satisfaction and HbA1c levels and body weight were analyzed using the Spearman's rank-correlation coefficient. Results: Of the 221 patients enrolled, 188 completed the study. Mean HbA1c decreased from 7.8 ± 0.7% (62.1 ± 7.5 mmol/mol) to 7.3 ± 0.8% (55.9 ± 8.7 mmol/mol) (change - 0.6 ± 0.7%, P < 0.001) and body weight decreased from 82.5 ± 14.6 to 80.7 ± 14.8 kg (change - 2.3 ± 2.8 kg, P < 0.001). OHA-Q ver. 2 was validated as well, the mean OHA-Q ver. 2 total score increased from 44.3 ± 9.4 to 46.6 ± 9.8 (best score 69, worst score 0; change 2.3 ± 6.6, P < 0.001). The change in body weight significantly correlated with the OHA-Q ver. 2 total score (Spearman's ρ = - 0.17, P = 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman's ρ = - 0.19, P = 0.011). Conclusions: Dapagliflozin significantly improved treatment satisfaction among patients with type 2 diabetes mellitus for 14 weeks. Body weight loss significantly correlated with treatment satisfaction.Trial registration UMIN-CTR: UMIN000016304.博士（医学）・甲第694号・平成31年3月15日© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

上皮成長因子受容体を標的とした結腸直腸腫瘍の分子イメージング : 動物モデルにおける腫瘍の検出と治療評価

To overcome the problem of overlooking colorectal tumors, a new and highly sensitive modality of colonoscopy is needed. Moreover, it is also important to establish a new modality to evaluate viable tumor volume in primary lesions of colorectal cancer (CRC) during chemotherapy. Therefore, we carried out molecular imaging of colorectal tumors targeting epidermal growth factor receptor (EGFR), which is highly expressed on tumor cells, for evaluating chemotherapeutic efficacy and for endoscopic detection of colorectal adenomas. We first attempted to image five CRC cell lines with various levels of EGFR expression using an Alexa Fluor‐labeled anti‐EGFR monoclonal antibody (AF‐EGFR‐Ab). A strong fluorescence signal was observed in the cells depending on the level of EGFR expression. When nude mice xenografted with LIM1215 CRC cells, which highly express EGFR, were i.v. injected with AF‐EGFR‐Ab, a strong fluorescence signal appeared in the tumor with a high signal to noise ratio, peaking at 48 hours after injection and then gradually decreasing, as shown using an IVIS Spectrum system. When the xenografted mice were treated with 5‐fluorouracil, fluorescence intensity in the tumor decreased in proportion to the viable tumor cell volume. Moreover, when the colorectum of azoxymethane‐treated rats was observed using a thin fluorescent endoscope with AF‐EGFR‐Ab, all 10 small colorectal adenomas (≤3 mm) were detected with a clear fluorescence signal. These preliminary results of animal experiments suggest that EGFR‐targeted fluorescent molecular imaging may be useful for quantitatively evaluating cell viability in CRC during chemotherapy, and also for detecting small adenomas using a fluorescent endoscope

Preparation of porous thin-film polymethylsiloxane microparticles in a W/O emulsion system

Porous thin-film polymethylsiloxane microparticles have been prepared successfully from octyltrichlorosilane and methyltrichlorosilane in (water/oil) W/O emulsion systems by using several oil phases and changing the amount of the silanes or of the surfactant Span 60. Hollow microspheres of various shell thicknesses (120-180 nm) and high surface area were prepared by using four types of nonpolar solvents as the oil phase of the W/O emulsion system. The diameter of the spheres can also be controlled (1-1.6 mu m) by using different oil phases. The results of thermal analysis, nitrogen adsorption isotherm, infrared spectra and X-ray diffraction data showed that hollow microspheres of amorphous polymethylsiloxane with high surface area (360-385 m(2)g(-1)) can be obtained by heating the spheres in air at 673 K; the polymethylsiloxane microspheres become nonporous silica particles after calcination at 873 K for 3 h. Cup-shape microparticles of polymethylsiloxane with nano-order thickness (20-120 nm) were prepared by reducing the amount of silanes in the mixture. Small hollow particles were prepared by replacing a portion of the octyltrichlorosilane with Span 60.ArticlePOLYMER JOURNAL. 47(6): 449-455 (2015)journal articl

Cancer genome profiling for GI cancers

In Japan, cancer genome profiling (CGP) for cancer patients without standard treatment has been covered by public insurance since June 2019. This study analyzed data of 122 patients with gastrointestinal tumors who underwent CGP to clarify cancer genome medicine’s current status and possible problems at the Tokushima University Hospital. The major types of cancer included pancreatic (n = 30), colorectal (n = 25), biliary tract (n = 15), gastric (n = 11), and hepatocellular carcinoma (n = 8). CGP tests included F1CDx in 70 patients (57%), F1LCDx in 36 (30%), TSO500 in 14 (11%), and NCC Oncopanel in 2 (2%). Actionable gene alterations were identified in 72 patients (59%), but only 5 patients (4%) were treated for pancreatic (n = 1), colorectal (n = 3), and small bowel cancers (n = 1). The main reasons for not receiving genotype-matched therapy included the lack of appropriate drugs or clinical trials that matched the actionable gene alterations (n = 40) and the inability to participate in clinical trials (n = 10). There is still not a sufficient number of patients receiving genotype-matched treatment for gastrointestinal cancers. To promote cancer genome medicine in regional areas, attempts to improve access to genotype-matched therapies are required, as well as to promote the development of new molecular-targeted drugs and clinical trials for these drugs