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Nanako Miwa,1 Tatsuya Nagano,1 Naoe Jimbo,2 Ryota Dokuni,1 Tatsunori Kiriu,1 Chihiro Mimura,1 Yuichiro Yasuda,1 Masahiro Katsurada,1 Masatsugu Yamamoto,1 Motoko Tachihara,1 Yugo Tanaka,3 Kazuyuki Kobayashi,1 Tomoo Itoh,2 Yoshimasa Maniwa,3 Yoshihiro Nishimura1 1Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; 2Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan; 3Division of Thoracic Surgery, Kobe University Graduate School of Medicine, Kobe, JapanCorrespondence: Tatsuya Nagano Tel +81 78 382 5660Fax +81 78 382 5661Email tnagano@med.kobe-u.ac.jpPurpose: Caspase recruitment domain-containing protein 9 (CARD9) is expressed at high levels in bone marrow cells and has a crucial role in innate immunity. Current studies indicate that CARD9 also plays a key role in tumor progression, but there are few reports on the role of CARD9 in lung cancer. The aim of this study was to clarify the role of CARD9 in lung adenocarcinoma.Patients and Methods: Lung adenocarcinoma tumor samples from 74 patients who underwent complete resection at Kobe University Hospital from January 2014 to December 2014 were analyzed by immunohistochemistry. The role of CARD9 in cancer cells was analyzed using lung cancer cell lines treated with CARD9 siRNA.Results: High expression of CARD9 was observed in 32.4% of tumors, and compared to low expression of CARD9, high expression was associated with poorer overall survival (P = 0.0365). Univariate and multivariate analyses showed that high expression of CARD9 was an independent prognostic factor. Knockdown of CARD9 in lung adenocarcinoma cells inhibited proliferation but did not increase apoptosis. In addition, CARD9 activated the NF-κB pathway in a lung adenocarcinoma cell line.Conclusion: CARD9 was shown to be an independent prognostic factor of poor outcome for lung cancer and may represent a molecular target for treatment.Keywords: CARD9, lung adenocarcinoma, spiral array, immunohistochemistry

A universal and consistent stage classification system, which describes the anatomic extent of a cancer, provides a foundation for communication and collaboration. Thymic epithelial malignancies have seen little progress, in part because of the lack of an official system. The International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group assembled a large retrospective database, a multispecialty international committee and carried out extensive analysis to develop proposals for the 8th edition of the stage classification manuals. This tumor, node, metastasis (TNM)-based system is applicable to all types of thymic epithelial malignancies. This article summarizes the proposed definitions of the T, N, and M components and describes how these are combined into stage groups. This represents a major step forward for thymic malignancies.

The lack of an official-stage classification system for thymic malignancies is an issue that hampers progress in this rare disease. A collaborative effort by the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group is underway to develop proposals for such a system. A database of more than 10,000 cases worldwide has been assembled to provide a solid basis for analysis. This report outlines the structure of the effort and the process that has been designed.

13C, 1H, and 39K-NMR measurements of (NH3)K3C60 unambiguously demonstrated that its magnetic properties are described as a S=1/2 localized spin system over the entire temperature range (300 K–4.2 K). A possible antiferromagnetic structure that appeared below 45 K is compatible with the orientational order of K-NH3 pairs on the octahedral (O) site. The present NMR study strongly suggests that the Mott-Hubbard localization occurs due to the removal of the C60 t1u-orbital degeneracy.

A 13C-NMR anisotropic hyperfine coupling tensor was determined as 2π(-1.68, -1.68, 3.37)×106 rad/sec for C603- in A3C60 superconductors, where A is an alkali metal, by analyzing 13C-NMR spectra below 85 K. Combined with an isotropic coupling constant of (2π×0.69)×106 rad/sec, the 2s and 2p characters of the electronic wave functions at the Fermi level were deduced. The results were compatible with local-density-approximation band calculations. From a simulation of 13C-NMR spectra at superconducting state, the traceless chemical (orbital) shift tensor and isotropic chemical shift were determined as (67, 34, -101) ppm and ∼150 ppm, respectively. An estimated magnetic penetration depth is larger than 570 nm in K3C60. Furthermore, the modified Korringa relation, T1TK2∼βS (with Knight shift K, spin-lattice relaxation time T1, and Korringa constant S), clearly showed the existence of weak but substantial antiferromagnetic spin fluctuation in A3C60; β=0.40–0.58 with an error of ±20%.0 The Stoner enhancement factor was also determined as 1–1.5 from a comparison between spin susceptibility obtained from NMR and band-calculation results.

The human DNA damage sensors, Rad17-replication factor C (Rad17-RFC) and the Rad9-Rad1-Hus1 (9-1-1) checkpoint complex, are thought to be involved in the early steps of the DNA damage checkpoint response. Rad17-RFC and the 9-1-1 complex have been shown to be structurally similar to the replication factors, RFC clamp loader and proliferating cell nuclear antigen polymerase clamp, respectively. Here, we demonstrate functional similarities between the replication and checkpoint clamp loader/DNA clamp pairs. When all eight subunits of the two checkpoint complexes are coexpressed in insect cells, a stable Rad17-RFC/9-1-1 checkpoint supercomplex forms in vivo and is readily purified. The two individually purified checkpoint complexes also form a supercomplex in vitro, which depends on ATP and is mediated by interactions between Rad17 and Rad9. Rad17-RFC binds to nicked circular, gapped, and primed DNA and recruits the 9-1-1 complex in an ATP-dependent manner. Electron microscopic analyses of the reaction products indicate that the 9-1-1 ring is clamped around the DNA.

Dc-magnetization and NMR measurements were carried out on a layered superconductor Li0.48(THF)yHfNCl having Tc∼26 K. For the magnetic field applied perpendicular to the basal plane (ab plane) above 10 kOe, we found a pronounced broadening of the superconducting transition in temperature dependence of magnetization and the substantial diamagnetic signals were observed as high as 2Tc, indicating the existence of superconducting fluctuations. Analysis based on the anisotropic Ginzburg-Landau model reveals that the present system is a highly anisotropic superconductor. 7Li-NMR signals were observed around zero Knight shift, indicating that the local Fermi-level density of states, N(EF), at Li site is practically nothing and the superconductivity is derived from the HfNCl layer. We have shown the unambiguous evidence for the quasi-two-dimensional superconducting character in this system.

We report magnetic susceptibility measurements on a layered superconductor Li0.48(THF)0.3HfNCl having Tc∼26 K. The present study revealed that (a) the Fermi level density of states is small, N*(EF)∼0.25 states/(eV spin f .u.), (b) mass enhancement is negligible, γ̃∼1, (c) electron-phonon coupling is weak, λep≪1, (d) exchange enhancement is negligible, 1/(1+F0a)∼1, and (e) electronic density parameter is large, rs2D∼10.3 (i.e., low-carrier density). It is difficult to explain the origin of the high Tc in terms of the conventional phonon (BCS) mechanism of superconductivity.