Nectin-like molecule-5 (Necl-5) is an immunoglobulin (Ig)-like molecule that is up-regulated in many types of cancer cells. It was shown experimentally that Necl-5 enhances cell migration, proliferation, and metastasis, but its clinical significance has not been documented. The aim of this study was to observe the expression of Necl-5 in surgically resected primary lung adenocarcinomas and to investigate its clinical significance. A total of 63 surgically resected primary pulmonary adenocarcinoma tissues were investigated by immunohistochemistry for the expression of Necl-5. The relationship between expression of Necl-5 and clinicopathological features was analyzed, and the influence of Necl-5 expression on outcomes in these patients was assessed. A strong expression of Necl-5 by cancer cells was observed in 43 of the 63 tumors. The overexpression of Necl-5 by cancer cells was significantly associated with lymph node metastasis (P = 0.0398), TNM staging (P = 0.0367), and the bronchioloalveolar carcinoma ratio of tumors (P = 0.0423). Furthermore, the disease-free survival rate in patients with positive Necl-5 overexpression was significantly lower than that in patients with negative Necl-5 overexpression (P = 0.0004). Multivariate survival analysis revealed Necl-5 expression to be an independent risk factor for an unfavorable outcome (P = 0.0294). Additionally, an analysis including only the stage I cases revealed that the diseasefree survival rate of the Necl-5-positive group was significantly lower than that of the Necl-5-negative group (P = 0.0192). These results indicate that Necl-5 plays a role in mediating tumor cell invasion and that the overexpression of Necl-5 in cancer cells has clinical significance for prognostic evaluation of patients with primary pulmonary adenocarcinoma. (Cancer Sci 2010; 101: 1326-1330 N ecl-5 ⁄ poliovirus receptor (PVR) ⁄ CD155 ⁄ Tage4 is an immunoglobulin(Ig)-like molecule with a domain structure consisting of one extracellular region with three Ig-like loops, one transmembrane region, and one cytoplasmic region.(1) Human PVR ⁄ CD155 was originally identified as the PVR in a screen of genomic DNA from cells susceptible to poliovirus infection.(2,3) Rodent Tage4 was originally identified in the rat by monoclonal antibody screens to isolate tumor-specific markers of hepatocellular carcinoma (4) and colon carcinoma.(5-8)Tage4 was also found to be expressed in fetal rat liver.PVR ⁄ CD155 was subsequently shown to be overexpressed in many human cancer cells. (9)(10)(11) The PVR ⁄ CD155 gene thus far has been found only in primates and the Tage4 gene has been found only in rodents, but these genes are likely to be derived from a common ancestral gene; (12,13) therefore, PVR ⁄ CD155 and Tage4 were renamed nectin-like molecule-5, or Necl-5. (1,14) Nectins are Ca 2+ -independent Ig-like cell-cell adhesion molecules.(1) Nectin-like molecules (Necls) have been designated as a group of Ig-like molecules with domain structures similar to, but slightly different from, those of nectin.(1)The p...

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DNA damage response pathways are important for maintaining genomic stability. The oncogenic phosphatase Wip1 plays a crucial role in DNA damage response by inhibiting several cell cycle proteins, including p53. Although Wip1 gene amplification has been reported in various primary tumors, including lung cancer, its biological significance for survival of primary lung tumor patients remains unclear. We investigated the expression of Wip1 in cancer epithelial cells immunohistochemically in 84 consecutive resected cases of lung adenocarcinoma. Increased Wip1 expression was observed in 54 (64.3%) of the 84 cases. Wip1 expression was found to be correlated significantly with two clinicopathological factors: c-H2AX expression, and invasion to the pulmonary vein. A univariate analysis and log-rank test indicated a significant association between Wip1 expression and lower overall survival rate (P = 0.019 and P = 0.0099, respectively). A multivariate analysis also indicated a statistically significant association between increased Wip1 expression and lower overall survival rate (hazard ratio, 4.3; P = 0.026). The Ki67 index level was higher in the Wip1-positive group than in the negative group (P < 0.04, Mann-Whitney U-test). Moreover, in a subgroup analysis of only stage I patients, increased Wip1 expression was also significantly associated with a lower overall survival rate (P = 0.023, log-rank test). These results indicate that the increased expression of Wip1 in cancer epithelial cells has significant value for tumor progression and the clinical prognosis of patients with primary lung adenocarcinoma. (Cancer Sci 2011; 102: 1101-1106 C ellular DNA is constantly exposed to various environmental and endogenous mutagenic insults. To maintain genomic integrity and prevent cancers caused by these potentially mutagenic events, a sophisticated array of damage sensors, signaling molecules, and repair functions have evolved. Among the key sensors of DNA damage are the phosphoinositide-3-kinaserelated kinase family, which includes ATM (ataxia-telangiectasia mutated), ATR (ataxia-telangiectasia and Rad3-related), and DNA-PK cs (DNA-dependent protein kinase catalytic subunit).(1,2) A direct role for the ATM ⁄ ATR-initiated damage response pathways in cancer prevention has been recently determined.(3,4) Human pre-neoplastic lesions from a variety of different human cancers were shown to express various markers reflecting responses to DNA damage response, including activated and phosphorylated ATM, Chk2, p53, and H2AX. (3,4) In particular, phosphorylated H2AX (called c-H2AX) plays a crucial role in recruiting DNA damage response factors to damage sites for accurate DNA repair and is considered a specific and sensitive molecular marker of DNA damage and repair. Interestingly, late-stage tumors often show loss of these DNA damage response markers, suggesting that a decrease in the activity of DNA damage response pathways may contribute to cancer progression. (3,4) Wild-type p53-induced phosphatase 1 (Wip1), also called PPM1D, is a me...

We studied absorption spectra near the band gap of GaAs/AlGaAs multiple quantum wells subjected to strong single-cycle terahertz pulses. With an increasing terahertz electric field, the heavy-hole 1s exciton energy near the band gap redshifts, reaches a maximum, and turns to blueshift. The blueshift increases proportionally to the ponderomotive energy, i.e., the terahertz electric field squared, which differs from the response expected from the Frantz–Keldysh effect (FKE) in a dc electric field. This fact suggests that the observed ponderomotive energy dependence of the blueshift can be ascribed to the dynamical FKE.

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