Nonmagnetic Ground State in RuO_{2} Revealed by Muon Spin Rotation.

The magnetic ground state of single crystalline RuO_{2} was investigated by the muon spin rotation and relaxation (µSR) experiment. The spin precession signal due to the spontaneous internal magnetic field B_{loc}, which is expected in the magnetically ordered phase, was not observed in the temperature range 5-400 K. Muon sites were evaluated by first-principles calculations using dilute hydrogen simulating muon as pseudohydrogen, and B_{loc} was simulated for the antiferromagnetic structures with a Ru magnetic moment |m_{Ru}|≈0.05µ_{B} suggested from diffraction experiments. As a result, the possibility was ruled out that muons are localized at sites where B_{loc} accidentally cancels. Conversely, assuming that the slow relaxation observed in µSR spectra was part of the precession signal, the upper limit for the magnitude of |m_{Ru}| was estimated to be 4.8(2)×10^{-4}µ_{B}, which is significantly less than 0.05µ_{B}. These results indicate that the antiferromagnetic order, as reported, is unlikely to exist in the bulk crystal.

Impact of hospital volume on risk-adjusted mortality following oesophagectomy in Japan.

BACKGROUND: Previous studies have reported that patients undergoing oesophagectomy in high-volume hospitals experience lower mortality rates. However, there has been ongoing discussion regarding the validity of evidence for this association. The purpose of this study was to investigate the relationship between hospital volume and risk-adjusted mortality following oesophagectomy in Japan, using a nationwide web-based database. METHODS: The study included patients registered in the database as having undergone oesophagectomy with reconstruction between 2011 and 2013. Outcome measures were 30-day and operative mortality rates. Logistic regression analysis was used to adjust for hospital volume, surgeon volume and risk factors for mortality after oesophagectomy. RESULTS: A total of 16 556 oesophagectomies at 988 hospitals were included; the overall unadjusted 30-day and operative mortality rates were 1·1 and 3·0 per cent respectively. The unadjusted operative mortality rate in hospitals performing fewer than ten procedures per year (5·1 per cent) was more than three times higher than that in hospitals conducting 30 or more procedures annually (1·5 per cent). Multivariable models indicated that hospital volume had a significant effect on 30-day (odds ratio 0·88 per 10-patient increase; P = 0·012) and operative (odds ratio 0·86 per 10-patient increase; P < 0·001) mortality. CONCLUSION: In Japan, high-volume hospitals had lower risk-adjusted 30-day and operative mortality rates following oesophagectomy compared with low-volume hospitals.

miR-9-3p plays a tumour-suppressor role by targeting TAZ (WWTR1) in hepatocellular carcinoma cells.

BACKGROUND: The inactivation of the Hippo pathway lead to TAZ (PDZ-binding motif)/YAP (yes-associated protein) overexpression, and is associated with worse prognostic outcomes in various cancers including hepatocellular carcinoma (HCC). Although there are several reports of microRNA (miR) targeting for YAP, miR targeting for TAZ remains unclear. The aim of this study is to identify the miR targeting TAZ expression in HCC. METHODS: MicroRNA expression was analysed using the Human miFinder 384HC miScript miR PCR array, and was compared between low and high TAZ expression cell lines. Then, we extracted miR-9-3p as a tumour-suppressor miR targeting TAZ. We examined the functional role of miR-9-3p using miR-9-3p mimic and inhibitor in HCC cell lines). RESULTS: In HCC cell lines and HCC clinical samples, there was the inverse correlation between miR-9-3p and TAZ expressions. TAZ expression was induced by treatment of miR-9-3p inhibitor and was downregulated by treatment of miR-9-3p mimic. Treatment of miR-9-3p mimic inhibited cell proliferative ability with downregulated phosphorylations of Erk1/2, AKT, and ß-catenin in HLF. Inversely, treatment of miR-9-3p inhibitor accelerated cell growth compared with control in HuH1. CONCLUSIONS: MicroRNA-9-3p was identified as the tumour-suppressor miR targetting TAZ expression in HCC cells.

Circulating Tumor Cells as an Independent Predictor of Survival in Advanced Gastric Cancer.

BACKGROUND: When the indication for surgery of highly advanced gastric cancer is considered, careful selection of the patients is important. In addition to tumor-node-metastasis factors and peritoneal lavage cytology (CY), which are important predictors of prognosis, detection of circulating tumor cells (CTCs) could be another potential marker. METHODS: This study prospectively evaluated CTCs using a semi-automated immunomagnetic separation system (CellSearch) for 136 patients with advanced gastric cancer to determine the frequency of CTC positivity. For 123 patients who also had their CY evaluated, the significance of both CTC and CY, was investigated as a potential biomarker to predict progression-free survival (PFS) or to monitor the therapeutic effect. RESULTS: In 25 patients (18.4 %), CTCs were positive. Positive CTC counts were more common for tumors with diffuse histologic type and distant metastasis. The PFS of CTC-positive patients was significantly shorter than that of CTC-negative patients (hazard ratio 2.03; P = 0.016). A multivariate analysis of 123 patients showed that CTC and CY as well as performance status and macroscopic distant metastasis were independent factors for PFS. When both CTC and CY were converted to negative values by therapeutic interventions, long-term PFS was achieved. CONCLUSIONS: Detection of CTCs was an independent predictor of a shorter PFS in advanced gastric cancer. For selecting patients who require intensive treatment, CTCs could be a valuable biomarker. The combined status of CTC and CY would be useful in selecting patients for radical surgery. Further investigation with a larger number of patients is necessary to establish the importance of CTCs.

CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma.

BACKGROUND: Circulating tumour cells (CTCs) have an important role in metastatic processes, but details of their basic characteristics remain elusive. We hypothesised that CD44-expressing CTCs show a mesenchymal phenotype and high potential for survival in hepatocellular carcinoma (HCC). METHODS: Circulating CD44(+)CD90(+) cells, previously shown to be tumour-initiating cells, were sorted from human blood and their genetic characteristics were compared with those of tumour cells from primary tissues. The mechanism underlying the high survival potential of CD44-expressing cells in the circulatory system was investigated in vitro. RESULTS: CD44(+)CD90(+) cells in the blood acquired epithelial-mesenchymal transition, and CD44 expression remarkably increased from the tissue to the blood. In Li7 and HLE cells, the CD44(high) population showed higher anoikis resistance and sphere-forming ability than did the CD44(low) population. This difference was found to be attributed to the upregulation of Twist1 and Akt signal in the CD44(high) population. Twist1 knockdown showed remarkable reduction in anoikis resistance, sphere formation, and Akt signal in HLE cells. In addition, mesenchymal markers and CD44s expression were downregulated in the Twist1 knockdown. CONCLUSIONS: CD44s symbolises the acquisition of a mesenchymal phenotype regulating anchorage-independent capacity. CD44s-expressing tumour cells in peripheral blood are clinically important therapeutic targets in HCC.

Robustness of basal-plane antiferromagnetic order and the J(eff)=1/2 state in single-layer iridate spin-orbit Mott insulators.

The magnetic structure and electronic ground state of the layered perovskite Ba(2)IrO(4) have been investigated using x-ray resonant magnetic scattering. Our results are compared with those for Sr(2)IrO(4), for which we provide supplementary data on its magnetic structure. We find that the dominant, long-range antiferromagnetic order is remarkably similar in the two compounds and that the electronic ground state in Ba(2)IrO(4), deduced from an investigation of the x-ray resonant magnetic scattering L(3)/L(2) intensity ratio, is consistent with a J(eff)=1/2 description. The robustness of these two key electronic properties to the considerable structural differences between the Ba and Sr analogues is discussed in terms of the enhanced role of the spin-orbit interaction in 5d transition metal oxides.

Cathepsin K expression in basal cell carcinoma.

BACKGROUND: Cathepsin K is a cysteine protease with strong collagenolytic and elastolytic properties. Recently, cathepsin K expression in tumour cells of malignant melanoma and in the stromal cells of squamous cell carcinoma of the skin has been reported to play an important role in tumour progression. However, its expression profile in basal cell carcinoma (BCC) has not yet been clarified. OBJECTIVE: The aim of this study is to examine the expression profile of cathepsin K in both the tumour cells and the peritumoural stromal cells of BCC in comparison with its expression in normal skin. METHODS: Fifty consecutive operative cases of BCC, 10 cases of actinic keratosis, 10 cases of Bowen's disease and five normal skin tissues were assessed for cathepsin K expression by immunohistochemical methods. RESULTS: In normal skin, cathepsin K expression was observed in the stratum corneum, mature sebaceous cells and outer root sheath of the hair follicles. Cathepsin K was expressed in the tumour cells of all BCC cases, in which 90% showed diffuse expression (>51% of tumour cells), as well as in the peritumoural stromal cells in all BCC cases. Focal cathepsin K expression was observed in the tumour cells of Bowen's disease (2/10 cases), but not in any of actinic keratosis (0/10 cases). CONCLUSION: Cathepsin K expression may contribute to tumour invasion and peculiar histopathological features, such as fibromucinous stroma around the tumour nests by mediating extracellular matrix degradation in BCC.

Upregulation of ERCC1 and DPD expressions after oxaliplatin-based first-line chemotherapy for metastatic colorectal cancer.

BACKGROUND: The updated randomised phase 2/3 FIRIS study demonstrated the noninferiority of IRIS (irinotecan and S-1) to FOLFIRI (irinotecan, folinic acid, and 5-FU) for metastatic colorectal cancer. Meanwhile, in the subset analysis including patients who previously have undergone oxaliplatin-containing chemotherapy, the IRIS group showed longer survival than the FOLFIRI group. However, the molecular mechanism underlying this result is still unknown. METHODS: The National Cancer Institute 60 (NCI60) cell line panel data were utilised to build the hypothesis. A total of 45 irinotecan-naive metastatic colorectal cancer patients who had undergone hepatic resection were included for the validation study. The mRNA expressions of excision repair cross-complementing group 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), and topoisomerase-1 (TOP1) were evaluated by quantitative RT-PCR. The expressions of ERCC1 and DPD were also evaluated by immunohistochemistry. RESULTS: Sensitivity to oxaliplatin in 60 cell lines was significantly correlated with that of 5-FU. Resistant cells to oxaliplatin showed significantly higher ERCC1 and DPD expression than sensitive cells. In validation study, ERCC1 and DPD but not TOP1 expressions in cancer cells were significantly higher in FOLFOX (oxaliplatin, folinic acid, and 5-FU)-treated patients (N=24) than nontreated patients (N=21). The ERCC1 and DPD protein expressions were also significantly higher in FOLFOX-treated patients. CONCLUSION: The ERCC1 and DPD expression levels at both mRNA and protein levels were significantly higher in patients with oxaliplatin as a first-line chemotherapy than those without oxaliplatin. The IRIS regimens with the DPD inhibitory fluoropyrimidine may show superior activity against DPD-high tumours (e.g., tumours treated with oxaliplatin) compared with FOLFIRI.