ヒト肺サーファクタントの免疫組織学的研究およびその法医学への応用

Pulmonary surfactant is believed to contribute to decrease the alveolar surface tension to maintain the alveolar spaces. Monoclonal antibodies against human pulmonary surfactant apoproteins of 34-37 kDa were prepared. Indirect immunocytochemistry using this antibody was performed on the paraffin sections of pulmonary tissue obtained from newborns, stillborns and infants at autopsy. Results showed the staining profiles of newborn and stillborn specimens to be slightly different from those of infants, and also to be altered according to the degree of alveolar expansion or degeneration and/or putrefaction. The author confirmed the existence of apoproteins even in the putrefied pulmonary tissue of a case examined at 3 or 4 months after death. This staining method clarified that a newborn had died of Respiratory Distress Syndrome, ruling out the first suspected cause of infanticide. This paper discussed the usefulness of the antibody and its application to legal medicine

HBx and c-MYC Cooperate to Induce URI1 Expression in HBV-Related Hepatocellular Carcinoma

Unconventional prefoldin RNA polymerase II subunit 5 interactor (URI1) has emerged as an oncogenic driver in hepatocellular carcinoma (HCC). Although the hepatitis B virus (HBV) represents the most common etiology of HCC worldwide, it is unknown whether URI1 plays a role in HBV-related HCC (HCC-B). In the present study, we investigated URI1 expression and its underlying mechanism in HCC-B tissues and cell lines. URI1 gene-promoter activity was determined by a luciferase assay. Human HCC-B samples were used for a chromatin immunoprecipitation assay. We found that c-MYC induced URI1 expression and activated the URI1 promoter through the E-box in the promoter region while the HBx protein significantly enhanced it. The positivity of URI1 expression was significantly higher in HCC-B tumor tissues than in non-HBV-related HCC tumor tissues, suggesting that a specific mechanism underlies URI1 expression in HCC-B. In tumor tissues from HCC-B patients, a significantly higher level of c-MYC was recruited to the E-box than in non-tumor tissues. These results suggest that HBx and c-MYC are involved in URI1 expression in HCC-B. URI1 expression may play important roles in the development and progression of HCC-B because HBx and c-MYC are well-known oncogenic factors in the virus and host, respectively

NEAT1 is Required for the Expression of the Liver Cancer Stem Cell Marker CD44

CD44, a cancer stem cell (CSC) marker, is required for maintaining CSC properties in hepatocellular carcinoma (HCC). Nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), is an oncogenic driver in HCC. In the present study, we investigated the significance of the NEAT1 gene in association with CD44 expression in liver CSCs of human HCC cell lines. The CSC properties were evaluated by spheroid culture, CSC marker expression, and sensitivity to anti-cancer drugs. The expression of both NEAT1 variant 1 (NEAT1v1) and variant 2 (NEAT1v2) as well as CD44 was significantly increased in the spheroid culture, compared with that in monolayer culture. Overexpression of Neat1v1, but not Neat1v2, enhanced the CSC properties, while knockout of the NEAT1 gene suppressed them. CD44 expression was increased by the overexpression of Neat1v1 and abrogated by NEAT1 knockout. The overexpression of NEAT1v1 restored the CSC properties and CD44 expression in NEAT1-knockout cells. NEAT1v1 expression in HCC tissues was correlated with poor prognosis and CD44 expression. These results suggest that NEAT1v1 is required for CD44 expression. To our surprise, NEAT1v1 also restored the CSC properties even in CD44-deficient cells, suggesting that NEAT1v1 maintains the properties of CSCs in a CD44-independent manner

Suppressive Effect of Juzentaihoto on Vascularization Induced by B16 Melanoma Cells In Vitro and In Vivo

Juzentaihoto (JTT) is well known to be one of Japanese herbal medicines, and used for the supplemental therapy of cancer patients with remarkable success. The present study, therefore, was undertaken to examine the possible therapeutic mechanisms of JTT on cancer using B16 melanoma cell (B16 cell)/experimental mouse system. JTT was well mixed with rodent chow at 3.0% concentrations, and was administered orally ad libitum. Administration of JTT was started one week before tumor cell injection and continued throughout the experiment. Administration of JTT into mice significantly inhibited tumor metastasis in lungs after intravenous injection of 2 × 105 B16 cells in a volume of 50 μL. JTT also significantly suppressed enlargement of tumor size in hind footpad after the subcutaneous injection of 2 × 105 (50 μL) B16 cells. In the second part of experiments, the chamber that containing B16 cells was buried in the murine back. In JTT administrated group, vascular endothelial growth factor (VEGF) of chamber internal fluid significantly decreased, and vascularization of chamber circumference was also inhibited. These results strongly suggest that oral administration of JTT caused decrease in the generation of VEGF, which is responsible for vascularization, and results in inhibition of B16 cell metastasis

Electron effective mass in Sn-doped monoclinic single crystal β\beta-gallium oxide determined by mid-infrared optical Hall effect

The isotropic average conduction band minimum electron effective mass in Sn-doped monoclinic single crystal $\beta$-Ga$_2$O$_3$ is experimentally determined by mid-infrared optical Hall effect to be $(0.284\pm0.013)m_{0}$ combining investigations on ($010$) and ($\bar{2}01$) surface cuts. This result falls within the broad range of values predicted by theoretical calculations for undoped $\beta$-Ga$_2$O$_3$. The result is also comparable to recent density functional calculations using the Gaussian-attenuation-Perdue-Burke-Ernzerhof hybrid density functional, which predict an average effective mass of $0.267m_{0}$ (arXiv:1704.06711 [cond-mat.mtrl-sci]). Within our uncertainty limits we detect no anisotropy for the electron effective mass, which is consistent with most previous theoretical calculations. We discuss upper limits for possible anisotropy of the electron effective mass parameter from our experimental uncertainty limits, and we compare our findings with recent theoretical results

Completion of the first ITER toroidal field coil structure

本論文は、日本が100%調達責任を有するITERのトロイダルコイル構造物の第1号機の完成を報告するものである。主な技術的な課題は、(i)極低温(4K)でも高い延性を持つ新規材料の開発、(ii)部分溶け込み溶接の適用、(iii)溶接変形対応、(iv)オーステナイトステンレス鋼溶接部の減衰効果を加味した超音波探傷試験法の開発、(v)巨大で複雑なD形状構造物の封止溶接開先の0.5mmオーダー公差での開先合わせ、などである。これらの各技術課題を解決し、ITER　TFコイル構造物第1号機は成功裏に完成することができた

Utility and Limitation of Preoperative Neutrophil Lymphocyte Ratio as a Prognostic Factor in Hepatocellular Carcinoma

【Background】 The neutrophil lymphocyte ratio (NLR) has been proposed to be a surrogate marker of inflammation and immunological status and to have prognostic value in various malignancies. This study was conducted to clarify the prognostic significance of preoperative NLR in hepatocellular carcinoma (HCC). 【Methods】 We enrolled 135 patients with histologicallyproven HCC who underwent initial curative hepatectomy. Based on the median NLR values, patients were divided into: NLR ? 2.0 (NLR-high, n = 69) and NLR < 2.0 (NLR-low, n = 66). 【Results】 In univariate analysis, the 5-year overall survival (OS) rates were 59.8 % ± 6.7% and 75.6% ± 6.5% (P = 0.028) in the NLR-high and NLR-low groups, respectively. Furthermore, the 5-year disease specific survival rates were 68.6% ± 6.7%, and 81.2 ± 6.4% (P = 0.048) in the NLR-high and NLR-low groups, respectively. 【Conclusion】 Our results showed that high NLR was an independent predictor for OS in hepatectomy-treated HCC, suggesting that NLR may be a novel prognostic biomarker for HCC. On the other hand, NLR also has a limitation to predict postoperative prognosis of HCC patients by itself

Clinical Significance of Serum Antithrombin III Activity After Hepatectomy for Hepatocellular Carcinoma

[Background] As antithrombin III (AT-III) is produced in the hepatocytes, its serum activity decreases at the time of liver failure, in addition to ischemia reperfusion injury, vascular endothelial dysfunction, and disseminated intravascular coagulation (DIC). Here, we examined whether the serum AT-III value after hepatectomy could be a prognostic factor for hepatocellular carcinoma (HCC). [Methods] Of 141 patients who underwent hepatectomy for HCC, data for 101 patients in whom serum AT-III activity was measured on the first postoperative day were extracted. Patients with serum AT-III activity > 50% and ? 50% were assigned to high value (72 cases) and low value (29 cases) groups, respectively. We examined the clinical and prognostic differences between these two groups. [Results] The average age of enrolled patients (83 men and 18 women) was 68.0 years. The 5-year overall survival rate was 88% and 60% in the high and low value groups, respectively (P < 0.01). Furthermore, the 2-year relapse-free survival rate was 71% and 54% in the high and low value groups, respectively (P = 0.03). [Conclusion] This is the first study to demonstrate that serum AT-III levels on the first postoperative day may serve as a prognostic factor in HCC patients

Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma

Background & AimsObesity defined by body mass index (BMI) significantly increases the risk of hepatocellular carcinoma (HCC). In contrast, not only obesity but also underweight is associated with poor prognosis in patients with HCC. Differences in body composition rather than BMI were suggested to be true determinants of prognosis. However, this hypothesis has not been demonstrated conclusively.MethodsWe measured skeletal muscle index (SMI), mean muscle attenuation (MA), visceral adipose tissue index, subcutaneous adipose tissue index, and visceral to subcutaneous adipose tissue area ratios (VSR) via computed tomography in a large-scale retrospective cohort of 1257 patients with different stages of HCC, and comprehensively analyzed the impact of body composition on the prognoses.ResultsAmong five body composition components, low SMI (called sarcopenia), low MA (called intramuscular fat [IMF] deposition), and high VSR (called visceral adiposity) were significantly associated with mortality, independently of cancer stage or Child-Pugh class. A multivariate analysis revealed that sarcopenia (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.18–1.96; p=0.001), IMF deposition (HR, 1.34; 95% CI, 1.05–1.71; p=0.020), and visceral adiposity (HR, 1.35; 95% CI, 1.09–1.66; p=0.005) but not BMI were significant predictors of survival. The prevalence of poor prognostic body composition components was significantly higher in underweight and obese patients than in normal weight patients.ConclusionsSarcopenia, IMF deposition, and visceral adiposity independently predict mortality in patients with HCC. Body composition rather than BMI is a major determinant of prognosis in patients with HCC