Roundabout relaxation: collective excitation requires a detour to equilibrium

Relaxation to equilibrium after strong and collective excitation is studied, by using a Hamiltonian dynamical system of one dimensional XY model. After an excitation of a domain of $K$ elements, the excitation is concentrated to fewer elements, which are made farther away from equilibrium, and the excitation intensity increases logarithmically with $K$. Equilibrium is reached only after taking this ``roundabout'' route, with the time for relaxation diverging asymptotically as $K^\gamma$ with $\gamma \approx 4.2$.Comment: 4 pages, 5 figure

Detection of deviance in Japanese kanji compound words

Reading fluency is based on the automatic visual recognition of words. As a manifestation of the automatic processing of words, an automatic deviance detection of visual word stimuli can be observed in the early stages of visual recognition. To clarify whether this phenomenon occurs with Japanese kanji compounds-since their lexicality is related to semantic association-we investigated the brain response by utilizing three types of deviants: differences in font type, lexically correct or incorrect Japanese kanji compound words and pseudo-kanji characters modified from correct and incorrect compounds. We employed magnetoencephalography (MEG) to evaluate the spatiotemporal profiles of the related brain regions. The study included 22 adult native Japanese speakers (16 females). The abovementioned three kinds of stimuli containing 20% deviants were presented during the MEG measurement. Activity in the occipital pole region of the brain was observed upon the detection of font-type deviance within 250 ms of stimulus onset. Although no significant activity upon detecting lexically correct/incorrect kanji compounds or pseudo-kanji character deviations was observed, the activity in the posterior transverse region of the collateral sulcus (pCoS)-which is a fusiform neighboring area-was larger when detecting lexically correct kanji compounds than when detecting pseudo-kanji characters. Taken together, these results support the notion that the automatic detection of deviance in kanji compounds may be limited to a low-level feature, such as the stimulus stroke thickness.Peer reviewe

Antitumor effect after radiofrequency ablation of murine hepatoma is augmented by an active variant of CC chemokine ligand 3/macrophage inflammatory protein-1á

金沢大学医薬保健研究域医学系Several chemokines are used for immunotherapy against cancers because they can attract immune cells such as dendritic and cytotoxic T cells to augment immune responses. Radiofrequency ablation (RFA) is used to locally eliminate cancers such as hepatocellular carcinoma (HCC), renal cell carcinoma, and lung cancer. Because HCC often recurs even after an eradicative treatment with RFA, additional immunotherapy is necessary. We treated tumor-bearing mice by administering ECI301, an active variant of CC chemokine ligand 3, after RFA. Mice were injected s.c. with BNL 1ME A.7R.1, a murine hepatoma cell line, in the bilateral flank. After the tumor became palpable, RFA was done on the tumor of one flank with or without ECI301. RFA alone eliminated the treated ipsilateral tumors and retarded the growth of contralateral non-RFA-treated tumors accompanied by massive T-cell infiltration. Injection of ECI301 augmented RFA-induced antitumor effect against non-RFA-treated tumors when administered to wild-type or CCR5-deficient but not CCR1-deficient mice. ECI301 also increased CCR1-expressing CD11c+ cells in peripheral blood and RFA-treated tumors after RFA. Deficiency of CCR1 impairs accumulation of CD11c+, CD4+, and CD8+ cells in RFA-treated tumors. Furthermore, in IFN-ã-enzyme-linked immunospot assay, ECI301 augmented tumor-specific responses after RFA whereas deficiency of CCR1 abolished this augmentation. Thus, we proved that ECI301 further augments RFA-induced antitumor immune responses in a CCR1-dependent manner. ©2010 AACR

Myeloid-derived suppressor cells correlate with patient outcomes in hepatic arterial infusion chemotherapy for hepatocellular carcinoma

Hepatic arterial infusion chemotherapy (HAIC) has been employed as an alternative therapy to sorafenib for the patients with advanced hepatocellular carcinoma (HCC). In this study, we performed a comparative analysis of various immune cell responses including tumor-associated antigen (TAA)-specific T cells, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in advanced HCC patients treated with HAIC. Thirty-six HCC patients were examined in the study. Interferon gamma enzyme-linked immunospot assays were performed to examine the frequency of TAA-specific T cells. The frequencies of Tregs and MDSCs were examined by multicolor fluorescence-activated cell sorting analysis. The treatment with HAIC using interferon (IFN)/5-fluorouracil (FU) or IFN/FU + cisplatin modulated the frequencies of various immune cells. In 22.2 % of patients, the frequency of TAA-specific T cells increased after HAIC. Although the frequency of Tregs decreased after HAIC, it was not associated with the prognosis of patients. An analysis of prognostic factors for overall survival identified diameter of the tumor (<3.0 cm), absence of major portal vein invasion, absence of distant metastasis, Union Internationale Contre Le Cancer tumor lymph node metastasis stage (I or II), neutrophil lymphocytic ratio (<2.1) and the frequency of MDSCs (<30.5 %) as factors that prolonged overall survival time after HAIC. Even in the group adjusted with progressive levels of tumors, patients with a low frequency of MDSCs had a significantly longer overall survival time. In conclusion, the frequency of MDSCs before the treatment is a prognostic factor in HAIC against HCC. © 2016 Springer-Verlag Berlin Heidelber

Phase I trial of multidrug resistance-associated protein 3-derived peptide in patients with hepatocellular carcinoma

Multidrug resistance-associated protein 3 (MRP3) is a carrier-type transport protein belonging to the ABC transporters. In this study, we investigated the safety and immunogenicity of a MRP3-derived peptide (MRP3765) as a vaccine and characterized the MRP3-specific T cell responses induced. Twelve hepatocellular carcinoma (HCC) patients treated with hepatic arterial infusion chemotherapy (HAIC) were enrolled. The MRP3-derived peptide was emulsified in incomplete Freund\u27s adjuvant and administered via subcutaneous immunization three times weekly. No serious adverse drug reactions to the peptide vaccine were observed, and the vaccination was well tolerated. The vaccination induced MRP3-specific immunity in 72.7% of the patients. In a phenotypic analysis, the largest post-vaccinated increase in MRP3-specific T cells was due to an increase in cells with the effector memory phenotype. Among the 12 patients, one patient showed a partial response, nine showed a stable disease, and two showed a progressive disease. The median overall survival time was 14.0 months. In conclusion, the safety, effects of immune boosting, and possible prolongation of overall survival by the MRP3-derived peptide demonstrate the potential of the peptide to provide clinical benefit in HCC patients. © 2015

Feasibility and efficacy of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma after sorafenib

Aim: Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC). However, although there is no proven therapeutic procedure following the termination of sorafenib, hepatic arterial infusion chemotherapy (HAIC) may be a treatment option in advanced HCC. The aim of this study was to evaluate feasibility and efficacy of HAIC for patients with advanced HCC as subsequent therapy. Methods: We retrospectively evaluated 27 consecutive patients with advanced HCC who were treated with HAIC following sorafenib between June 2009 and December 2012 at our hospital. Cisplatin (20 mg/m2 per day) was administered via the hepatic artery for 10 min, prior to the continuous administration of 5-fluorouracil (330 mg/m2 per day) over 24 h from days 1-5 and 8-12 and the s.c. administration of pegylated interferon α-2b (1 μg/kg) on days 1, 8, 15, and 22. A treatment cycle consisted of 28 days of drug administration followed by 14 days of rest. Results: The toxicity profile showed that hematological toxicities were common, and grade 3/4 neutropenia and thrombocytopenia were observed (51.9% and 48.1%, respectively). Five patients (18.5%) experienced device-related complications. No unexpected adverse reactions and no treatmentrelated deaths were observed. Partial response was obtained in eight patients (29.6%), and stable disease was noted in nine patients (33.3%). Median progression-free survival and median survival time from initiation of HAIC were 4.0 and 7.6 months, respectively. Conclusions: Because HAIC was well tolerated and exhibited moderate antitumor activity, it is a potentially useful treatment procedure in patients with advanced HCC even after failure of sorafenib