Metastases of soft tissue sarcoma to the liver: A Historical Cohort Study from a Hospital-based Cancer Registry

Background: Hepatic metastasis of soft tissue sarcoma is rare compared to lung metastasis, and the literature is scarce. We examined the risk of hepatic metastasis according to the site of occurrence and histological type. Methods: From a Hospital-based Cancer Registry, 658 patients registered between 2007 and 2017 with soft tissue sarcomas were evaluated. The exclusion criteria were gastrointestinal stromal tumors, tumors of unknown origin, and follow-up periods of less than 1 month. SPSS 25 was used for statistical analysis. Results: The risk of hepatic metastasis was significantly higher in the retroperitoneum (HR, 5.981; 95% CI, 2.793-12.808) and leiomyosarcoma (HR, 4.303; 95% CI, 1.782-10.390). Multivariate analysis showed that the risk of hepatic metastasis as first distant metastasis was high in leiomyosarcoma (HR, 4.546; 95% CI, 2.275-9.086) and retroperitoneal onset (HR, 4.588; 95% CI, 2.280-9.231). The 2-year survival rate after hepatic metastasis was 21.7%. Conclusions: The onset of hepatic metastasis indicates a poor prognosis. However, hepatic metastasis from retroperitoneal sarcoma and leiomyosarcoma may be the first distant metastasis in some cases. For retroperitoneal sarcoma and leiomyosarcoma, additional screening for hepatic metastasis such as contrast CT should be considered during staging and follow-up after treatment.ArticleCancer medicine 17(17) : 6159-6165(2020)journal articl

Continuous Observations of the Ground Deformations Related to the Matsushiro Earthquakes

In order to investigate the relations between ground deformations and seismic activities in Matsushiro and neighbouring regions, continuous observations on the ground tilt and strain were carried out at Matsushiro and Suzaka. At Matsushiro, three tiltmeters of horizontal pendulum type and two extensometers of bow-string type were installed in the underground gallery bored into Zozan hill, the western suburb of Matsushiro Town. At Suzaka, two tiltmeters of water tube type and two tiltmeters of horizontal pendulum type were installed in the underground gallery bored halfway up Kamatayama hill, the western suburb of Suzaka City. As to Matsushiro, it was observed that the velocity of the ground tilt sometimes changed before the occurrence of an earthquake. As to Suzaka, it proved that the direction of the ground tilt changed markedly every time an earthquake of a magnitude larger than 5.0 occurred, and an anomalous ground tilt appeared before the occurrence of the earthquakes of Sep. 27, 1966, and Feb. 8, 1967

In vitro evaluation method for screening of candidate prebiotic foods

AbstractThe aim of this work was to develop a simple and rapid in vitro evaluation method for screening and discovery of uncharacterised and untapped prebiotic foods. Using a NMR-based metabolomic approach coupled with multivariate statistical analysis, the metabolic profiles generated by intestinal microbiota after in vitro incubation with feces were examined. The viscous substances of Japanese bunching onion (JBOVS) were identified as one of the candidate prebiotic foods by this in vitro screening method. The JBOVS were primarily composed of sugar components, especially fructose-based carbohydrates. Our results suggested that ingestion of JBOVS contributed to lactate and acetate production by the intestinal microbiota, and were accompanied by an increase in the Lactobacillus murinus and Bacteroidetes sp. populations in the intestine and fluctuation of the host-microbial co-metabolic process. Therefore, our approach should be useful as a rapid and simple screening tool for potential prebiotic foods

Structural Basis of the Autophagy-Related LC3/Atg13 LIR Complex: Recognition and Interaction Mechanism

SummaryAutophagy is a bulk degradation pathway that removes cytosolic materials to maintain cellular homeostasis. The autophagy-related gene 13 (Atg13) and microtubule associate protein 1 light chain 3 (LC3) proteins are required for autophagosome formation. We demonstrate that each of the human LC3 isoforms (LC3A, LC3B, and LC3C) interacts with Atg13 via the LC3 interacting region (LIR) of Atg13. Using X-ray crystallography, we solved the macromolecular structures of LC3A and LC3C, along with the complex structures of the LC3 isoforms with the Atg13 LIR. Together, our structural and binding analyses reveal that the side-chain of Lys49 of LC3 acts as a gatekeeper to regulate binding of the LIR. We verified this observation by mutation of Lys49 in LC3A, which significantly reduces LC3A positive puncta formation in cultured cells. Our results suggest that specific affinity of the LC3 isoforms to the Atg13 LIR is required for proper autophagosome formation

PREDICTION SYSTEMS FOR BLADDER CANCER THERAPY

The present study established systems to predict the chemo‑sensitivity of muscle invasive bladder cancer (MIBC) for neoadjuvant chemotherapy (NAC) with methotrexate, vinblastine, doxorubicin plus cisplatin (M‑VAC) and carboplatin plus gemcitabine (CaG) by analyzing microarray data. The primary aim of the study was to investigate whether the clinical response would increase by combining these prediction systems. Treatment of each MIBC case was allocated into M‑VAC NAC, CaG NAC, surgery, or radiation therapy groups by their prediction score (PS), which was calculated using the designed chemo‑sensitivity prediction system. The therapeutic effect of the present study was compared with the results of historical controls (n=76 patients) whose treatments were not allocated using the chemo‑sensitivity prediction system. In addition, the overall survival between the predicted to be responder (positive PS) group and predicted to be non‑responder (negative PS) group was investigated in the present study. Of the 33 patients with MIBC, 25 cases were positive PS and 8 were negative PS. Among the 25 positive PS cases, 7 were allocated to receive M‑VAC NAC and 18 were allocated to receive CaG NAC according to the results of the prediction systems. Of the 8 negative PS cases, 3 received CaG NAC, 1 received surgery without NAC and 4 received radiation therapy. The total clinical response to NAC was 88.0% (22/25), which was significantly increased compared with the historical controls [56.6% (43/76) P=0.0041]. Overall survival of the positive PS group in the study was significantly increased compared with the negative PS group (P=0.027). In conclusion, the combination of the two prediction systems may increase the treatment efficacy for patients with MIBC by proposing the optimal NAC regimen. In addition, the positive PS group would have a better prognosis compared with the negative PS group. These results suggest that the two prediction systems may lead to the achievement of ‘precision medicine’

Biological responses according to the shape and size of carbon nanotubes in BEAS-2B and MESO-1 cells

This study aimed to investigate the influence of the shape and size of multi-walled carbon nanotubes (MWCNTs) and cup-stacked carbon nanotubes (CSCNTs) on biological responses in vitro. Three types of MWCNTs - VGCF (R)-X, VGCF (R)-S, and VGCF (R) (vapor grown carbon fibers; with diameters of 15, 80, and 150 nm, respectively) - and three CSCNTs of different lengths (CS-L, 20-80 mu m; CS-S, 0.5-20 mu m; and CS-M, of intermediate length) were tested. Human bronchial epithelial (BEAS-2B) and malignant pleural mesothelioma cells were exposed to the CNTs (1-50 mu g/mL), and cell viability, permeability, uptake, total reactive oxygen species/superoxide production, and intracellular acidity were measured. CSCNTs were less toxic than MWCNTs in both cell types over a 24-hour exposure period. The cytotoxicity of endocytosed MWCNTs varied according to cell type/size, while that of CSCNTs depended on tube length irrespective of cell type. CNT diameter and length influenced cell aggregation and injury extent. Intracellular acidity increased independently of lysosomal activity along with the number of vacuoles in BEAS-2B cells exposed for 24 hours to either CNT (concentration, 10 mu g/mL). However, total reactive oxygen species/superoxide generation did not contribute to cytotoxicity. The results demonstrate that CSCNTs could be suitable for biological applications and that CNT shape and size can have differential effects depending on cell type, which can be exploited in the development of highly specialized, biocompatible CNTs.ArticleINTERNATIONAL JOURNAL OF NANOMEDICINE. 9:1979-1990 (2014)journal articl

DJ-1 as a potential biomarker for the development of biocompatible multiwalled carbon nanotubes

Hisao Haniu1, Tamotsu Tsukahara2, Yoshikazu Matsuda3, Yuki Usui4, Kaoru Aoki5, Masayuki Shimizu5, Nobuhide Ogihara5, Kazuo Hara5, Seiji Takanashi5, Masanori Okamoto5, Norio Ishigaki5, Koichi Nakamura5, Hiroyuki Kato5, Naoto Saito6 1Institute of Carbon Science and Technology, 2Department of Integrative Physiology and Bio-System Control, Shinshu University, Matsumoto, Nagano, 3Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Ina-machi, Saitama, 4Research Center for Exotic Nanocarbons, 5Department of Orthopaedic Surgery, 6Department of Applied Physical Therapy, Shinshu University School of Health Sciences, Shinshu University, Matsumoto, Nagano, Japan Background: In the present study, we investigated whether DJ-1 could serve as a biomarker for assessing the biocompatibility of multiwalled carbon nanotubes (MWCNTs), using the highly purified carbon nanotube, HTT2800. Methods: Using Western blot analysis, we determined DJ-1 protein levels in two different types of cells (one capable and the other incapable of HTT2800 endocytosis). Using quantitative real-time polymerase chain reaction, we also investigated the ability of purified nanotubes to alter DJ-1 mRNA levels. Results: We demonstrated that the DJ-1 protein concentration was reduced, regardless of the cytotoxic activity of intracellular HTT2800. Furthermore, HTT2800 decreased the DJ-1 mRNA levels in a dose-dependent manner. This decrease in DJ-1 mRNA levels was not observed in the case of Sumi black or cup-stacked carbon nanotubes. Conclusion: These data indicate that modification of DJ-1 expression is caused by the cell response to MWCNTs. We conclude that DJ-1 is a promising candidate biomarker for the development of biocompatible MWCNTs. Keywords: multiwalled carbon nanotubes, DJ-1 protein, Western blot, quantitative real-time polymerase chain reactio

Preliminary Trial of Rebamipide for Prevention of Low-Dose Aspirin-Induced Gastric Injury in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study

Although low-dose aspirin is widely used, since it is a cheap and effective means of prevention of cardiovascular events, it can cause hemorrhagic gastrointestinal complications. The aim of this study was to evaluate the efficacy of rebamipide in preventing low-dose aspirin-induced gastric injury. A randomized, double-blind, placebo-controlled, crossover trial was performed in twenty healthy volunteers. Aspirin 81 mg was administered with placebo or rebamipide 300 mg three times daily for 7 consecutive days. The rebamipide group exhibited significant prevention of erythema in the antrum compared with the placebo group (p = 0.0393, respectively). Results for the body and fornix did not differ significantly between the placebo and rebamipide groups. In conclusion, short-term administration of low-dose aspirin induced slight gastric mucosal injury in the antrum, but not in the body or fornix. Rebamipide may be useful for preventing low-dose aspirin-induced gastric mucosal injury, especially which confined to the antrum