Introduction: Surgical resection with multidisciplinary therapy, so called conversion surgery is needed to improve the prognosis of patients with initially unresectable locally advanced (UR-LA) pancreatic ductal adenocarcinoma (PDAC). Method: Seventy-seven consecutive patients with UR-LA PDAC who were performed chemotherapy and/or followed by conversion surgery (CS) at Chiba University hospital from Jan 2010 to Dec 2019 were retrospectively analyzed. We assessed the clinical significance of CS, and compared the impact of efficacy between gemcitabine plus S-1 (GS) and gemcitabine plus nab-paclitaxel (GnP) before CS in UR-LA PDAC. Results: The patients were classified into CS (n=32) and non-CS group (n=45). Comparing between CS and non-CS group, the SMA involvement was significantly lower in CS (40.6%) than that in non-CS (64.4%) group (p=0.038). The median survival time (MST) for overall survival were 13.1 months for non-CS and 30.1 months for CS group (p<0.0001). Comparing chemotherapies between GS (n=35) and GnP group (n=41), the conversion rates were 54.3% (19/35) in GS and 29.3% (12/41) in GnP (p=0.027). The median percentage of tumor shrinkage were 23% for GS and 32% for GnP (p=0.047), the decrease rate of CA19-9 level were 74% for GS and 83% for GnP (p=0.37) in CS group. The Kaplan-Meier analysis revealed that the MST for overall survival were 14.3 months for GS and 12.0 months for GnP in non-CS, and 26.8 months for GS and 45.9 months for GnP in CS group. Conclusions: Randomized prospective studies will be warranted for the strategy of treatment for patients with UR-LA PDAC.

Background: Krüppel-like factor5 (KLF5) has been reported to be involved in tumorigenicity of intestinal epithelium and is a transcription factor that affects tumor growth, invasion, and metastasis. The liver is the most common site of distant metastases of colorectal cancer and colorectal liver metastases is an important factor affecting its prognosis. Therefore, we examined the correlation between KLF5 expression level in colorectal liver metastases and clinicopathological factors and prognosis. Methods: KLF5 expression was evaluated immunohistochemically using surgical specimens of 98 patients who underwent initial hepatectomy for colorectal liver metastases. Results: KLF5 expression was detected in the cytoplasm of cancer cells. Of 98 cases, KLF5 was highly expressed in 42 cases. The number of metastatic tumors was relatively higher in the KLF5 high expression group (P=0.171). The tumor diameter was significantly larger in the KLF5 high expression group (P=0.007). In addition, there was a positive correlation between KLF5 expression and Ki67 expression (P=0.007). Overall survival rate after initial hepatectomy was significantly worse in the KLF5 high expression group compared with the KLF5 low expression group (P=0.029). Time to surgical failure (TSF) was significantly short in the KLF5 high expression group (P=0.017). Univariate analysis demonstrated that administration of preoperative chemotherapy, use of molecular targeted reagent, high serum carcinoembryonic antigen level, lymph node metastases of primary lesion, number of tumor (4≤), tumor diameter (5cm≤) and high expression level of KLF5 were significantly associated with a poor prognosis. Multivariate analysis demonstrated that number of tumor (4≤), tumor diameter (5cm≤) and high expression of KLF5 were independent risk factors for poor prognosis (P=0.040, P=0.001, P=0.045, respectively). Conclusion: KLF5 expression is an independent prognostic factor of patients with colorectal liver metastases. A novel treatment targeting KLF5 may improve the prognosis of patients with colorectal liver metastases.

Patients: Twenty-four patients underwent hepatectomy for liver metastases after primary tumor resection for biliary tract cancer from 1999 to 2016. Results: There were 18 men and 6 women with a median age at hepatectomy of 68 years. The diagnoses were extrahepatic bile duct cancer in 14 cases, intrahepatic cholangiocarcinoma in 7 cases, gallbladder cancer in 2 cases, ampullary cancer in 1 case. The median interval from initial surgery for the primary tumor to recurrence was 22months. The number of tumors were one in 15 cases, 2 in 7 cases, 3 or more in 6 cases. The median tumor diameter was 23mm. Major hepatectomy for liver metastases was performed in 6 cases and minor hepatectomy in 22 cases. Operation time was 227minutes and blood loss was 845g. R0 resection was completed in 10 cases. Only one patient died of postoperative-liver failure within 90days. The median survival time (MST) and 1y-, 3y-overall survival (OS) after initial hepatectomy was 29months and 81.7%, 37.0%. On the other hand, the MST and 1y-, 3y-OS of patients who did not undergo hepatectomy for liver metastases were 8 months and 36.2%, 6.1%. Long-term outcome was significantly better in patients who underwent hepatectomy for liver metastases. Univariate analysis demonstrated that disease-free survival (DFS) after the initial surgery for the primary tumor, number of liver metastases, type of hepatectomy, and operation time of hepatectomy were significantly associated with the prognosis after initial hepatectomy. Repeat hepatectomy was performed in 4 cases with recurrent liver metastases. One patient with solitary metastasis is alive for 103months after the initial surgery for the primary tumor, 86months after the first hepatectomy and 48months after repeat hepatectomy. Conclusion: Favorable prognosis can be expected in selected patients with long DFS (more than 12months) and solitary metastasis which can be resected by minor hepatectomy.

Sago palm (Metroxylon sagu Rottb.) is distributed in Southeast Asia and Melanesia, and it produces comparatively high yield of starch (more than 200 kg per plant). This species can grow in wetland swamps where other food crops cannot grow economically and adapt to problem soils such as acid or saline with low input. The Society of Sago Palm Studies and the authors have published books entitled “The Sago Palm: The Food and Environmental Challenges of the 21st Century (Kyoto Univ. Press 2015)” and “Sago Palm: Multiple Contributions to Food Security and Sustainable Livelihoods (Springer 2018)”. This paper provides a brief review on (1) characteristics of seed germination and preparation of planting materials utilizing germinated seeds, (2) symbiosis of sago palm and microbes (nitrogen fixing bacteria or arbuscular mycorrhizal fungi), (3) creating new value from pith waste after conventional starch extraction (recovery of starch, ethanol production or preparation of biodegradable foam from the waste) and (4) utilization of leaf or bark from our former publications and the achievements published in our journal ‘SAGO PALM’ or the proceedings of the International Sago Symposium to discuss sustainable production and utilization of sago palm resource in Asia and Pacific.

Background We have identified leucine-rich alpha 2 glycoprotein (LRG) as a disease marker of rheumatoid arthritis (RA) 1). Although LRG is produced in site of inflammation such as synovial tissues, its function is still unclear. Recently, LRG is reported to bind with TGF-β and enhance of Smad2 phosphorylation 2). TGF-β is essential for differentiation of Th17. Th17 plays important roles in the pathogenesis of RA, for example, by regulating osteoclast differentiation. In collagen induced arthritis (CIA), a mouse model of RA, phosphorylation of Smad2 in CD4 T cells is important for the Th17 differentiation and the induction of arthritis 3). Thus, LRG may be involved in the pathogenesis of RA through the regulation of T lymphocyte differentiation. Objectives In this study, we aimed to elucidate the function of LRG on T lymphocyte differentiation and to examine the involvement of LRG in the pathogenesis of RA. Methods Naïve T lymphocyte were isolated from WT or LRG KO mice to examine the effects of LRG on the differentiation into Th17 and Treg in the absence or presence of recombinant LRG. Male C57BL/6 mice and LRG KO mice were subjected to collagen-induced arthritis (CIA). Results In the presence of TGF-β alone, the differentiation of Treg was promoted by LRG. However, in the presence both TGF-β and IL6, LRG enhanced the differentiation into Th17 by increasing both Smad2 and STAT3 phosphorylation. The phosphorylation of p38 was also increased by LRG. In addition, the expression of IL6 receptor in naïve T cells was significantly lower in LRG KO mice than in WT mice. In CIA model, arthritis score was significantly lower in LRG KO mice than in control group. The numbers of Th17 in regional lymph nodes and serum levels of IL17 were significantly lower in LRG KO mice than in WT mice. Conclusions LRG promoted TGF-β-induced Smad2 phosphorylation under Th17 differentiation condition. Since Smad2 signal increases the expression of IL6 receptor in naïve T cells 4), LRG might increase the expression of IL6 receptor through Smad2 signal, leading to enhanced the phosphorylation of STAT3 which is an essential transcription factor in the differentiation of Th17 4)5). LRG also enhanced phosphorylation of p38 MAPK which is involved in the proliferation of helper T cells. In addition, recent study reported that p38 MAPK plays an important role in the production of IL17 6)7) Taken together, our study suggested that LRG promotes both the proliferation and Th17 differentiation of naive T cells under inflammatory state, leading to deterioration of arthritis. References Ann Rheum Dis 2010 Oncotarget 2015 Nat Commun 2015 J Biol Chem 2010 Nat Commun 2015 J Immunol 2010 Blood 2011 Disclosure of Interest None declared

Background C-reactive protein (CRP) is frequently used to evaluate inflammation in patients with rheumatoid arthritis (RA). However, CRP is normalized when IL-6 function is potently suppressed by anti-cytokine biologics such as tocilizumab. Therefore, novel biomarkers are required for accurate and sensitive assessment of the inflammation during anti-cytokine therapy. By proteomic screening of sera from patients with rheumatoid arthritis (RA), we previously identified serum leucine-rich alpha-2 glycoprotein (LRG) as a potential biomarker that reflects disease activity in RA better than CRP. Objectives This study is aimed to investigate the clinical significance of LRG as a biomarker of RA disease activity during anti-IL-6 therapy. Methods As a preclinical testing, cynomolgus monkeys with collagen induced arthritis (CIA) were treated with anti-IL-6 receptor antibody (anti-IL-6R mAb) and joint swelling and rigidity were scored for clinical assessment of arthritis throughout the experiment. At the time of sacrifice, blood samples were collected to be subjected to the measurement of LRG and CRP. RA patients treated with tocilizumab were enrolled and clinical disease activity index (CDAI) and serum levels of LRG and CRP were evaluated. Results In CIA monkeys with anti-IL-6R mAb treatment, plasma LRG levels correlated better with disease activity than plasma CRP levels, presumably due to the fact that LRG levels were elevated in some animals with negative CRP in spite of high arthritis scores. Furthermore, among tocilizumab-treated patients for 6 months with normalized CRP levels (<0.2 mg/dL), serum LRG levels were significantly higher in patients with active RA (defined by CDAI>10) than those with RA with low disease activity (CDAI≤10). Conclusions Our study indicates that LRG is a promising biomarker for monitoring disease activity in RA, even when CRP levels are reduced or normalized by anti-cytokine therapy. References I Navarro-Millán et al. Systematic Review of Tocilizumab for Rheumatoid Arthritis: A New Biologic Agent Targeting the Interleukin-6 Receptor Clin Ther 2012; 34: 788-802 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2180

The water stability of sulfonated copolyimides (SPIs) derived from 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTDA), sulfonated diamines of 4,4‘-bis(4-aminophenoxy)biphenyl-3,3‘-disulfonic acid (pBAPBDS), and 2,2‘- or 3,3‘-bis(3-sulfopropoxy)benzidine (2,2‘- or 3,3‘-BSPB) and nonsulfonated diamines was investigated in detail from viewpoints of viscosity, mechanical strength, proton conductivity, weight loss, and hydrolysis products eluted into the soaking water. With the aging in water or 100% relative humidity vapor at 130 °C, the polymer chain scission took place mainly in the early stage but thereafter slightly, and as a result the SPI membranes kept the reasonably high mechanical properties even after 192 h. The branched/cross-linked SPI membranes prepared by incorporating a flexible triamine kept better mechanical properties. The weight loss and sulfur loss of <10% were observed for the pBAPBDS-based SPIs. This was due mainly to the elution of hydrolysis product, the oligomer of NTDA, and sulfon...

Acid-resistant residues (lintnerized starches, Ls) were prepared from starches showing A-, B- and C- X-ray diffraction patterns. Ls retained the same X-ray crystalline type as their native counterparts with an improvement in diffraction intensity. Fluorophore-assisted capillary electrophoresis (FACE) study indicated that structural characteristics of Ls were associated with X-ray diffraction patterns. Double helices originated from linear chains with an approximate average degree of polymerisation (DP) 14, 16, and 15 would span the entire length of crystalline lamellae of A-, B-, and C-type starches, respectively. The proportion of singly branched materials (SB) with DP 25 protected in Ls was higher for A-type Ls (10–17%) than for B-type Ls (4–6%) and C-type Ls (8%). The structures of SB were similar in which branched chain (DP 13–15) was longer than main chain (DP 10–12). The structural characteristics of Ls are discussed in relation to acid and enzymatic degradations of starch granules.

A series of sulfonated copolyimides (co-SPIs) bearing pendant sulfonic acid groups were synthesized from 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTDA), bis(3-sulfopropoxy) benzidines (BSPBs), and common nonsulfonated diamines via statistical or sequenced polycondensation reactions. Membranes were prepared by casting their m-cresol solutions. The co-SPI membrane had a microphase-separated structure composed of hydrophilic and hydrophobic domains, but the connecting behavior of hydrophilic domains was different from that of the homo-SPIs. The co-SPI membranes displayed clear anisotropic membrane swelling in water with negligibly small dimensional changes in the plane direction of the membrane. With water uptake values of 39-94 wt %, they showed dimensional changes in membrane thickness of about 0.11-0.58, which were much lower than those of homo-SPIs. The proton conductivity sigma, values of co-SPI membranes with ion exchange capacity values ranging from 1.95-2.32 meq/g increased sigmoidally with increasing relative humidity. They displayed sigma values of 0.05-0.16 S/cm at 50 degrees C in liquid water. Increasing temperature up to 120 degrees C resulted in further increase in proton conductivity. The co-SPI membranes showed relatively good conductivity stability during the aging treatment in water at 100 degrees C for 300 h. (c) 2005 Wiley Periodicals, Inc.

Two types of sulfonated co-polyimides (co-SPIs) with ion exchange capacities of 1.83–2.32meq/g were prepared from 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTDA), two types of sulfonated diamines, namely, 4,4′-bis(4-sulfophenoxy)biphenyl-3,3′-disulfonic acid (BAPBDS) and bis(3-sulfopropoxy)benzidines (BSPBs), and common non-sulfonated diamines via statistical polycondensation reaction. The BSPB-based co-SPI membranes had a clear microphase-separated structure composed of hydrophilic and hydrophobic domains but the connection of hydrophilic domains was rather poor. On the other hand, the BAPBDS-based co-SPI membranes did not show such a clear microphase separation. The co-SPI membranes except for a few ones showed high proton conductivities of 0.10–0.16S/cm in water at 323K, which was comparable to that of Nafion 112 (0.13S/cm). The methanol permeabilities of the co-SPI membranes hardly depended on feed composition up to 50wt.% of methanol and were in the range of 0.5×10−6 to 1.8×10−6cm2/s at 323K, which were more than two times smaller than those of Nafion 112. As a result, the co-SPI membranes showed more than two times larger ratios of proton conductivity over methanol permeability than Nafion, suggesting high potential for direct methanol fuel cell application.

Fifteen starches from different botanical sources were selected to study the influence of structural features on thermal properties and enzyme digestibility. Morphological appearance, X-ray diffraction pattern, apparent amylose content, unit-chain length distribution of amylopectin, thermal properties and enzyme digestibility of starch varied with botanical source. It was demonstrated that the distribution of unit-chains of amylopectin significantly correlated with functional properties of the starches. Gelatinization temperature of native and retrograded starches decreased and increased with a relative abundance of unit-chains with an approximate degree of polymerization (DP) of 8–12 and 16–26, respectively (P<0.01). Similar unit-chain lengths also affected the enzyme digestibility of starch granules (P<0.01).

Swelling and pasting properties of 15 starches from different plant origins were studied to elucidate their relationship with structural features using simple and multiple regression analyses. Avoidance of additional effects of starch minor components showed that swelling power and pasting parameters were associated with the ratio of the relative molar distribution of amylopectin branch-chains with a degree of polymerization (DP) of 6–12 to that of chains with DP 6–24 (amylopectin unit-chain (APC) ratio). Swelling power of starch granules increased with APC ratio. Multiple regression analysis revealed that the peak viscosity (PkV) of starch paste increased with low APC ratio, low amylose content (AC) and large average granule size (AGS). At a high starch concentration, pasting temperature (PT) was reduced by a high APC ratio and large AGS. Peak time (PkT) decreased with increasing APC ratio and AC. Percentage of breakdown viscosity (BD%) and setback viscosity (SB) were primarily affected by APC ratio. At a low concentration, AC and AGS had more profound effects on BD%. SB was also reduced by higher AC. Models of pasting profile, which is influenced by individual factors, were also proposed.

A method for assessing surface passivation, based on a measurement of V/sub oc/, is presented which is sensitive to SRV from 10 to 100,000 cm/s. V/sub oc/ for a back p-n junction cell is strongly dependent on carrier recombination at the front surface. By employing such a cell structure without a FSF diffused layer, this sensitivity of V/sub oc/ to front surface conditions is amplified. From a SiN/sub x//np/sup +//Al structure, an SRV of 2,000 cm/s was inferred for the lightly-doped (20 /spl Omega/-cm) n-type dendritic Web silicon surface passivated with a low frequency direct PECVD SiN/sub x/ layer. V/sub oc/ measurements were then used to optimize the n/sup +/ process in such a FSF cell to 75 /spl Omega///spl square/ via etchback, with consideration given to properly removing residue from the screen-printed phosphorus paste in order to present a clean n/sup +/ surface for SiN/sub x/ deposition and to assessing the impact of applying high SRV metal contacts to the front n/sup +/ surface. With this optimization, production-worthy thin dendritic Web silicon PhosTop cells having low-resistance contacts and an average efficiency tightly grouped around 14.4% were obtained.

A red yeast isolated from the acidic water of Kusatsu hot spring could grow in an acidic medium of pH 1.5 and was identified as Rhodotorula glutinis. Electron microscope observations (scanning electron microscopy [SEM] and transmission electron microscopy [TEM]) showed that cell envelope became wrinkled and thick as the pH values of media became lower. The cell membrane grown at pH 1.5 was about four times as thick as that grown at pH 6.0. It was suggested that the change of cell envelope plays an important role in the acid tolerance. Cellular proteins at pH 1.5 appeared to be different from those at pH 6.0 and the amounts of phospholipids and non-phospholipids increased and decreased under low pH conditions, respectively. The acid-tolerant yeast also showed strong resistance to both aluminum and manganese ions. An acidic medium (pH 3.0) containing these ions (100 mM) was shifted to neutral pH by long-term cultivation of the red yeast, suggesting the potential of using this yeast in the bioremediation of acidic soil containing these ions at a high level.

The adhesion of water-soluble β-d-glycans, including cellulose-adhesive schizophyllan, xyloglucan, and locust bean gum to intact cells and protoplasts of Nicotiana tabacum BY-2 was examined using their fluorescent derivatives. Fluorescence microscopy showed that schizophyllan, xyloglucan, locust bean gum, and xanthan gum bound to the intact cells, and that schizophyllan, xanthan gum, and succinoglycan bound to the protoplasts. These adhesive β-d-glycans raised considerably the number of the cells regenerated from protoplasts. The results suggest that some water soluble β-d-glycans showing affinity for intact cells and/or protoplasts will be suitable for use as stabilizers of protoplast division.