Given that clinical trials of poly ADP-ribose polymerase (PARP) 1 inhibitors are underway, in the present study we investigated the prevalence of triple-negative breast cancer and PARP1 expression in patients with primary invasive breast cancer. Immunohistological studies plus PARP staining were performed on samples from 206 primary breast cancer patients undergoing surgery at Showa University Hospital between January 2010 and May 2011. Fifteen patients (7.3%) were found to have triple-negative breast cancer. Hormone receptor-positive patients were significantly more likely to be PARP1 negative. There were no PARP1-negative patients in the triple-negative group. However, there was no significant difference in the rate of PARP1 negativity between patients with triple-negative breast cancer and those with other breast cancer subtypes. There were no PARP1-negative patients in the triple-negative breast cancer group. Given that the effectiveness of PARP inhibitors has not been sufficiently established in clinical trials, a more in-depth analysis is required to determine the factors contributing to effective treatment. Future studies should include more subjects with triple-negative breast cancer and those with BRCA mutations.

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Abstract: There have been many reports on the overexpression of human epidermal growth factor receptor 2 (HER2) in patients with colon cancer. However, the role and frequency of HER2 overexpression have not been clearly defined. Anti-HER2 therapy has been shown to improve the prognosis of HER2-positive patients with breast and stomach cancers. In this study, we explored HER2 expression in patients with colon cancer at stages II and III by immunohistochemistry (IHC) and dual-color in situ hybridization (DISH), and examined the correlation between HER2 expression and clinicopathological factors. Moreover, we examined the correlation between HER2 expression and mucin 1 (MUC1) expression. The subjects were 121 patients with colon cancer at stages II and III who underwent surgery in our hospital during the period from 2007 to 2009. Sections containing the deepest part of a lesion were subjected to immunostaining for HER2 and MUC1. HER2 expression was assessed in accordance with Ventana's Guidelines for HER2 Testing in Stomach Cancer, with sections comprising less than 10% of weakly to moderately stained tumor cells scored as 1 > 2. HER2 expression scored as 2 was defined with sections comprising more than 10% of the weakly to moderately stained tumor cells. Patients with a score of 1 > 2 and 2 were also subjected to DISH using a Dual ISH HER2 kit. MUC1 expression was scored according to the percentage of stained area as follows: 0, 0 to 5%; 1, 5 to 50%; and 2, 50% and higher. Patients with a score of 1 and 2 were defined as MUC1-positive. The analysis of HER2 by IHC yielded the following scores: 45 patients (37.2%), 0; 38 patients (31.4%), 1; 14 patients (11.6%); 1 > 2; 24 patients (19.8%), 2; and 0 patients (0%), 3. For the 38 patients with a score of 1 > 2 and 2, DISH returned ratios of HER2 to Chr17 expression (HER2: Chr17 ratio) from 1.13 to 1.93 (mean = 1.46). There was no significant correlation between HER2 expression and clinicopathological factors. The numbers of MUC1-positive patients according to HER2 score were as follows: 22 patients (48.9%) in the score 0 group (45 patients); 25 patients (65.8%) in the score 1 group (38 patients); 10 patients (71.4%) in the score 1 > 2 group (14 patients), and 22 patients (91.7%) in the score 2 group (24 patients). There was a positive correlation between HER2 expression and MUC1 expression. Specifically, MUC1 expression levels increased with HER2 expression level, and the percentage of MUC1-positive patients was significantly higher in the HER2 score 2 group than in the HER2 score 0 group (P < 0.01). Rates of HER2 positivity by DISH or fluorescence in situ hybridization (FISH) in patients who had an HER2 score of 2+ by IHC were 45% and 24% in the patients with stomach and breast cancers, respectively. However, the positivity rate was 0% in the patients with colon cancer in this study. This result indicates that patients with colon cancer who have an IHC HER2 score of 2+ are more likely to be HER2 negative by DISH than patients with breast and stomach cancers, although larger cohort studies are required before a definitive conclusion can be made. There was a positive correlation between HER2 expression and MUC1 expression in this study, although further examination is required because there were no patients who had an HER2 score of 3+ or 2+ by IHC and were HER2 positive by DISH in this study. HER2 expression in colon cancer should be cautiously assessed by both IHC and DISH.

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Cerebral palsy (CP) is a developmental disorder associated with lifelong motor impairment and disability. Several studies have investigated the effects of CP on sensory responses, but there has been no research on olfactory function in CP. This study had two specific aims. First, by observing respiratory responses which serve as an index for the ability to detect and recognize odors, we aimed to estimate the patients' ability to distinguish pleasant from unpleasant odors. These responses can also indicate the capacity for an emotional response to pleasant or unpleasant stimuli. Second, we aimed to investigate the psychological response in the parents as they observed the respiratory response in their children during the odor test. Parents were assessed with the Spielberger State-Trait Anxiety Inventory (STAI) to measure their state anxiety levels before and after they had observed their children being tested. In patients with CP, respiratory rate (RR) significantly decreased during pleasant odor stimuli (P < 0.05). There was a significant increase in RR during the presentation of the unpleasant odor (P < 0.05). All the CP patients showed respiratory changes in response to both pleasant and unpleasant smells, and we found that the parents' anxiety levels decreased after the test. We intend to develop this olfactory test technique to contribute to the neurological rehabilitation for CP patients and to reduce anxiety of their parents.

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DNA polymerase ζ (Pol ζ) participates in translesional bypass replication. Pol ζ has been shown to be an important contributor to cis-diamminedichloroplatinum (II)(DDP; cisplatin) -induced genomic instability and the subsequent emergence of resistance in vitro. We immunohistochemically examined the expression of Pol ζ in ovarian cancer tissues to determine whether its expression affects the DDP resistance of human ovarian cancers and also to determine whether Pol ζ expression is a prognostic factor for ovarian cancers. We assessed 76 archival, formalin-fixed, paraffin-embedded tissue samples obtained from patients with epithelial ovarian cancers who underwent their first operation between 2003 and 2011. An ovarian cancer tissue array was also used in this study. Immunohistochemical staining of Pol ζ was performed using an anti-human Pol ζ monoclonal rabbit antibody. The strength of expression of Pol ζ was compared with the DDP resistance and clinical features of the study population. The Pol ζ over-expression in ovarian cancer tissue which compared with epithelial cells in normal ovaries was not affected by the histological types, FIGO stage, or patient age, but Pol ζ was significantly more overexpressed in the DDP-resistant group than in the DDP-sensitive group (P = 0.043). Pol ζ over-expression did not significantly affect the survival rate of the ovarian cancer patients; however, the Pol ζ positive group tended to have a poorer long-term prognosis. In conclusion, ovarian carcinoma patients with Pol ζ over-expression are likely to be resistant to DDP, especially in cases of recurrent disease. These results confirm the previous findings in vitro, wherein Pol ζ modulated the cytotoxicity and mutagenicity of DDP.

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The goal of this study was to establish a normogram of the intracranial structure volumes in appropriate-for-gestational age (AGA) Japanese fetuses. This was a cross-sectional and prospective study of 211 AGA fetuses. The total intracranial, cerebrum, ventricle, choroid plexus, cerebellum, cerebellar vermis, and cavum septum pellucidum volumes were measured using three-dimensional (3D) ultrasound. The fetal cranial and intracranial structure volumes significantly increased with gestational age (GA). When using the GA as an independent variable and the fetal cranial or intracranial structure volumes as the dependent variable, the best-fit equation for the fetal brain was a second-order polynomial regression equation. We herein provide the first report of fetal cranial and intracranial structure volumes and their normal growth curves in normal Japanese fetuses. Future 3D ultrasound studies of volume and other intracranial fetal structures could provide valuable information about how such changes may correlate with long-term neurodevelopment and the results may be used for comparisons with fetal growth restriction in the future.

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Gastric cancers (GC) with methylation of multiple CpG islands have a CpG island methylator phenotype (CIMP) and they can have different biological features. The aim of this study was to investigate the DNA methylation status of GCs and its association with their clinicopathological features. We evaluated the methylation status of four genes (MINT1, MINT2, MINT25 and MINT31) in 105 primary GCs using bisulfite-pyrosequencing analysis. We classified tumors as CIMP-high (CIMP-H), CIMP-low (CIMP-L) or CIMP-negative (CIMP-N) based on the methylation of MINT1, MINT2, MINT25, and MINT31. Overall, the prevalence of CIMP-H, CIMP-L and CIMP-N was 22% (23/105), 52% (55/105) and 26% (27/105), respectively. We observed a significant difference in tumor stage (stages I-II vs. stages III-IV) between CIMP-H and CIMP-N tumors (P = 0.0435). No significant differences were observed in clinicopathological characteristics (gender, age, location and tumor differentiation) among the CIMP phenotypes. The prognoses of patients with a CIMP-H tumor is likely to be better than those with CIMP-L or CIMP-N tumors, but these differences are not statistically significant (P = 0.074 and P = 0.200). Our results suggest that CIMP may define a subgroup of GCs with distinct biological features.

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The expression of transcription factor forkhead box protein 3 (FOXP3), a master control gene for regulatory T cells, has been reported to influence patient survival. However, there have been few reports of the relationship between FOXP3 positive cells and esophageal squamous cell carcinoma (ESCC). The aim of this study was to clarify the prognostic value of FOXP3 expression in ESCC. Ninety-five patients who were diagnosed with primary ESCC and underwent subtotal esophagectomy during 2009 and 2010 were retrospectively analyzed. Deepest sections from each tumor were selected for immunohistochemistry and the number of FOXP3 positive cells was counted. The median number was used as a cutoff to divide into FOXP3 positive and FOXP3 negative subgroups. Relationships between FOXP3 expression and clinicopathological features, disease-free survival (DFS) and overall survival (OS) were determined. Statistical values of p < 0.05 were considered significant. FOXP3 positive cells were found in all 95 cases and the number of FOXP3 positive cells was significantly higher in the peri-tumor compartment than in the intra-tumor compartment (p = 0.0006). For this reason, the peri-tumor compartment numbers were used for all of the association studies. Results showed that the FOXP3 positive group had a significantly larger mean tumor size (43.8 ± 4.1mm vs 29.1 ± 4.0mm, p = 0.0055), and the FOXP3 negative group had a significantly higher percentage of deep invasion (T2, T3, T4)(p = 0.0399). There was no significant association for DFS, however, for OS the FOXP3 positive group demonstrated a significantly better prognosis (p = 0.0024). Multivariate analysis showed that peri-tumor FOXP3 expression is an independent prognostic factor for OS (p = 0.0035). Peri-tumoral FOXP3 expression is an independent and favorable prognostic factor for ESCC.

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We developed a grasping pin with a hook for osteosynthesis of proximal femoral fractures and compared its performance with that of a lag screw. Cyclic compressive tests were performed to simulate cut-outs, and quasi-static torsion, tests were conducted to simulate rotational displacement in polyurethane model bones and femoral heads collected after hip replacement surgery, and cadaveric femoral heads. In the polyurethane model bones and femoral head collected after hip replacement surgery, implant displacement was increased in the cut-out simulation test in both the grasping pin group and lag screw group, deformation was less in the grasping pin group than in the lag screw group. In polyurethane bones and cadaveric bones, the grasping pins showed higher rotational resistance compared with the lag screws in the quasi-static torsion test because of the high compression force generated during implantation. In contrast, in the collected femoral head after hip replacement surgery model, the lag screws destroyed bone tissue, the lag screw group exhibited a higher rotational resistance and a lower risk of rotational displacement than the grasping pin model. The depth of cadaveric femoral heads was 60mm compared with 30mm for femoral heads obtained after surgery; therefore, the pins could be completely inserted up to the octagonal portion in the cadaveric bones, resulting in higher rotational resistance.

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