Formation of lipid membrane‐incorporated small π‐molecules bearing hydrophilic groups

Nineteen poorly water‐soluble π‐conjugated molecules were evaluated in terms of their ability to be stably incorporated into lipid membranes. The resulting lipid membrane-incorporated π‐conjugated guest molecules (LMIGs) were classified into four categories, including (i) those that formed stable LMIGs; (ii) those where some of guest molecules precipitated; (iii) those that formed small self‐aggregates consisting of lipids and/or guest molecules; and (iv) those that leaked some of the guest molecules into the bulk water. Compounds belonging to category (ii) were confirmed by UV‐vis absorption analysis. In contrast, compounds belonging to categories (i), (iii) and (iv) were discriminated based on their 1H NMR spectra and the broadening or disappearance of the peaks of the guest molecules and the lipids in LMIGs and large liposomes. Several LMIGs could be converted from one category to another using other lipids. Furthermore, the guest molecules belonging to category (iv) were successfully predicted using the octanol‐water partition coefficient, which was calculated by simulation.This work was supported by the Japanese Society for the Promotion of Science (JSPS) KAKENHI Grant‐in‐Aid for Scientific Research (B) (Grant No. JP16H04133) and a Grant‐in‐Aid for Challenging Exploratory Research (Grant No. JP16K13982)

Oxygen reduction at negatively charged iron porphyrins heat-treated and bridged by alkaline-earth metal ions

金沢大学理工研究域物質化学系An ordered network of tetrasodium tetra(4-sulphonatophenyl)porphyrin iron(III) chloride (FeTPPS4Na4), which exhibited a higher catalytic activity for oxygen reduction than Co and Ir(CO)TPPS 4Na4, was fabricated by complexation with alkaline-earth metal ions. Heat treatment of these complexes enhanced their catalytic activity with the highest performance observed with Ba2+-FeTPPS4. The onset potential for oxygen reduction (Eonset) was 720mVvs. Ag|AgCl, which is almost the same as that for Pt-impregnated carbon black. The number of electrons, n, transferred during oxygen reduction at a Ba2+- FeTPPS4-coated electrode, as determined by rotating ring-disc experiments, was 3.9 and suggests that oxygen was reduced to water. A neutral solution of FeTPPS4Na4 was acidified by the addition of barium ion, and the elemental ratio Fe:S:Ba in the resulting Ba 2+-FeTPPS4 complex was approximately 1:4:2.5. This suggests the formation of a highly ordered network with Fe sites bridged with barium ions in addition to the normal salt bridges between sulphonates. Catalytic oxidation reactions with nitric oxide and nitrite ion as the intermediate at the heat-treated Ba2+-FeTPPS4 indicate the formation of Fe(IV) and Fe(IV) π-cation radicals or Fe(V). The agreement between the potential of Fe(IV) π-cation radical formation and E onset suggests that the redox cycle of the Fe(III)/Fe(IV) π-cation radical provides a sufficient driving force for the observed 4-electron reduction of oxygen at the heat-treated Ba2+-FeTPPS4 electrode. © 2010 Elsevier Ltd. All rights reserved

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)

Evaluation of Prognosis of Juvenile Differentiated Thyroid Carcinoma

Differentiated thyroid carcinoma (DTC) in juvenile patients is often an extensive and aggressive disease with a high frequency of recurrence. However, the prognosis is excellent, with a low mortality rate even when advanced disease is present, although prognostic factors and treatment strategy remain uncertain. Between April 2004 and March 2017, 33 juvenile patients (< 30 years old) were diagnosed with DTC and treated at our institution. We retrospectively investigated prognosis and factors including sex, reason for discovery, treatment, pathological factors and treatment progress to clarify the risk factors. All patients underwent curative surgical treatment. Pathologically, lymph node metastasis was identified in 25 patients (75%). Thirteen patients (39%) had bilateral cervical metastasis. In addition, 9 (27%) had more than 10 metastatic lymph nodes. The 2 patients with more than 20 metastatic lymph nodes were treated with radioactive iodine (RAI). Five patients (15%) had local recurrences and received surgery. There have been no further recurrences or deaths. However, no factors were determined to significantly predict the recurrence of juvenile DTC. Local recurrent disease was treated with surgery and/or RAI until remission, and survival was excellent in juvenile DTC

Influences of preoperative metformin on immunological factors in early breast cancer

Purpose Metformin has been suggested to possibly reduce cancer risk. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. We conducted a prospective study to evaluate the effects of preoperative metformin in patients with early breast cancer. Method We evaluated the effects on immunological factors (TILs, CD4 + , CD8 + , PD-L1, IFNγ and IL-2) by comparing core needle biopsies (CNB) obtained before metformin treatment with surgical specimens. Seventeen patients were enrolled in this prospective study from January to December 2016. We also analyzed 59 patients undergoing surgery during the same period to reveal the correlation of immune factors between CNB and surgical specimen. Result There was a moderate correlation between CNB and surgical specimens on TILs and CD8 + lymphocyte. (TILs Rs = 0.63, CD4 + Rs = 0.224, CD8 + Rs = 0.42) In the metformin group, TILs increases were confirmed in five (29%) patients, while a decrease was confirmed in two (12%). The expressions of CD4 + and CD8 + by TILs were increased in 41% and 18% of surgical specimens, respectively. However, TILs number (p = 0.0554), CD4+ (p = 0.0613) and CD8 + (p = 0.0646) expressions did not significantly increased. Furthermore, IFNγ expression appeared to be increased in response to metformin (p = 0.08). Conclusion Preoperative metformin tends to increase TILs, as well as the numbers of CD4 and CD8 positive lymphocytes, and IFNγ levels. Metformin might improve immune function and have a possibility of chemo-sensitivity and thereby increase the effectiveness of immunotherapy, based on the results of this preliminary study

Lipid-membrane-incorporated hydrophobic photochromic molecules prepared by the exchange method using cyclodextrins

It was found that the exchange method for the preparation of lipid-membrane-incorporated guest molecules was applicable not only to fullerenes but also to other hydrophobic molecules such as azobenzene and stilbene. Advantages of this method are that the long-term stability of lipid-membrane-incorporated azobenzene solution and the maximum ratio of [stilbene]/[lipid] were higher than those prepared by the classical method, which we call the ‘premixing method’. Photoisomerisations of these photochromic guest molecules in the lipid membranes maintained the morphology of liposomes.This file includes Electronic Supplementary Information.This work was supported by JSPS KAKENHI a Grant-in-Aid for Scientific Research (B) (Grant No. 25288037), a Grant-in-Aid for Challenging Exploratory Research (Grant Nos. 24655128 and 25650053) and a Grant-in-Aid for Young Scientists (A) (Grant No. 24681028)

Evaluation of Therapeutic Target Gene Expression Based on Residual Cancer Burden Classification After Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer

Introduction Patients with residual disease usually have a poor prognosis after neoadjuvant chemotherapy for breast cancer. The aim of this study was to explore therapeutic targets and potential additional adjuvant treatments for patients with residual disease after standard neoadjuvant chemotherapy. Patients and Methods We retrieved publicly available complementary DNA microarray data from 399 human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer samples from patients who underwent standard neoadjuvant chemotherapy. We analyzed the messenger RNA (mRNA) expression levels of key breast cancer markers and therapeutic target genes according to residual cancer burden (RCB) classification: RCB-0/I, RCB-II, and RCB-III. Results Among hormone receptor–positive samples, there were more luminal A tumors by PAM50 (Prediction Analysis of Microarray 50 [Prosigna], aka Prosigna Breast Cancer Prognostic Gene Signature Assay) in RCB-III than in RCB-0/I and RCB-II (P Conclusion In hormone receptor–positive breast cancer, biological features such as luminal A were associated with RCB; this trend was not observed in TN breast cancer. Further, some targeted therapies should be tested as new strategies after standard neoadjuvant chemotherapy in future clinical trials