DNA Damage Sensor γ

Background. Phosphorylated histone H2AX (γ-H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ-H2AX in hepatocellular carcinoma (HCC), we measured the level of γ-H2AX in HCC, dysplastic nodule, and nontumorous liver diseases. Methods. The level of γ-H2AX was measured by immunohistochemistry in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic nodules. Appropriate cases were also examined by fluorescence analysis and western blotting. Results. All cases with chronic liver disease showed increased levels of γ-H2AX expression. In 40 (69.9%) of 58 cases with HCC, the labeling index (LI) of γ-H2AX was above 50% and was inversely correlated with the histological grade. Mean γ-H2AX LI was the highest in dysplastic nodule (74.1±22.1%), which was significantly higher than HCC (P<0.005). Moreover, γ-H2AX was significantly increased in nontumorous tissues of HCC as compared with liver cirrhosis without HCC (62.5±24.7%, from 5.1 to 96.0%, P<0.005). Conclusions. γ-H2AX was increased in the preneoplastic lesions of HCC and might be a useful biomarker for predicting the risk of HCC

当院における便潜血陽性者に対する大腸CT(CTコロノグラフィー)検査の有用性:大腸がん検診への導入と課題

大腸がん検診におけるスクリーニング検査としての大腸CT(CT colonography: CTC)検査の有用性を検討するために,当院における便潜血陽性者に対するCTCと大腸内視鏡検査の精度比較を行った.2009年7月から2014年1月までに川崎医科大学附属病院で施行されたCTC検査673件中,スクリーニング目的で行われた411件の中で便潜血陽性者に対して行われた183名を対象とした.全例CTC検査と同日に全大腸内視鏡検査も行った.対象とする病変は内視鏡観察あるいは病理組織学的に腺腫,がんと診断されたものとした.CTCの前処置は,経口腸管洗浄剤に水溶性造影剤による標識(タギング)を付けて行った.CT装置は16列Multi-slice CT(MSCT),腸管拡張は自動炭酸ガス注入器を使用した.CTC読影は,まず仮想内視鏡(3D)で行い,後に多断面再構成像(Multi-planar reconstruction: MPR 像(2D))を行う3D primary 法で行った.183名(男性98名,女性85名,年齢40～86歳,平均年齢62.1歳±0.8歳)のうち,病変を認めなかったのは87名(47.5%)であり,病変を認めたのは96名(53%)であった.総病変数は191個であり,うち6mm以上の病変は77個(40%)で,そのうち10mm以上のものは46個(24%)であった.大腸癌は25例(全病変中13%)で,うち腺腫内癌16例(全病変中8%)であった.側方発育型腫瘍は8例(4%)(大きさ平均17mm)であった.病変のうち,内視鏡的切除が行われたものは34病変であり,手術が行われたものは22病変であった.病変形態別による描出率は隆起型病変80%で,平坦型病変65%であった.病変サイズ別の精度は10mm以上の病変(n=46)で感度96%,陽性適中率98%であり,6mm以上の病変(n=77)で感度83%,陽性適中率79%であった.CTCは便潜血陽性者において良好な精度を示し,大腸がんスクリーニング法としての可能性がある.The purpose of this study was to estimate the sensitivity and specificity of CT colonography (CTC) for colorectal cancer screeing following positive fecal occult blood test (FOBT) in Japan. To compare detection rates of colorectal cancer and adenoma between CTC and optical total colonoscopy (TCS). This study included 183 patients with positive result of FOBT in Japanese colorectal cancer screening program. The patients had both CTC and TCS on the same day. 96 patients (53%) had colorectal lesions, on the other hand 87 patients had no lesions. The total number of lesions was 191, including 77 lesions 6 mm in maximum diameter and larger, including 46 lesions 10 mm and larger

p27 Is a Critical Prognostic Biomarker in Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma

Non-alcoholic steatohepatitis (NASH) is a recently identified chronic liver disease, which progresses to liver cirrhosis and hepatocellular carcinoma (HCC). As the number of patients studied to date has been limited, clinically useful prognostic biomarkers of NASH-related HCC have not been available. In this study, we investigated the status of a cell-cycle regulator, p27, in NASH-related HCC. p27 has been regarded as a prognostic factor in various types of cancer patients. A total of 22 cases with NASH-related HCC were analyzed for p27 protein expression, and phosphorylation at threonine 157 (T157) and serine 10 (S10) by immunohistochemical analysis. The correlation of p27 with tumor characteristics, disease-free survival (DFS), and overall survival was analyzed. p27 expression was decreased in 13 HCCs (59%), and was significantly correlated with enlarged tumor size (p = 0.01) and increased cell proliferation (p &lt; 0.01). Phospho-p27 at T157 and S10 was detected in four (18%) and seven (32%) cases, respectively, and patients positive for phospho-p27 (S10) showed reduced DFS (hazard ratio 7.623, p = 0.016) by univariate analysis. Further studies with more patients are required to verify the usefulness of p27 as a biomarker for predicting tumor recurrence in NASH patients

Impact of linked color imaging and blue laser imaging on the diagnosis of esophageal squamous cell carcinoma in iodine unstained areas

Abstract The pink color sign in iodine unstained areas is useful to differentiate esophageal squamous cell carcinoma (ESCC) from other lesions. However, some ESCCs have obscure color findings which affect the ability of endoscopists to differentiate these lesions and determine the resection line. Using white light imaging (WLI), linked color imaging (LCI) and blue laser imaging (BLI), 40 early ESCCs were retrospectively evaluated using images before and after iodine staining. Visibility scores for ESCC by expert and non‐expert endoscopists were compared using these three modalities and color differences measured for malignant lesions and surrounding mucosa. BLI had the highest score and color difference without iodine staining. Each determination with iodine was much higher than without iodine regardless of the modality. With iodine, ESCC mainly appeared pink, purple and green using WLI, LCI and BLI, respectively and visibility scores determined by non‐experts and experts were significantly higher for LCI (both p < 0.001) and BLI (p = 0.018 and p < 0.001) than for WLI. The score with LCI was significantly higher than with BLI among non‐experts (p = 0.035). With iodine, the color difference using LCI was twice that with WLI and one with BLI was significantly larger than with WLI (p < 0.001). These greater tendencies were found regardless of location, depth of cancer or intensity of pink color using WLI. In conclusion, areas of ESCC unstained by iodine were easily recognized using LCI and BLI. Visibility of these lesions is excellent even by non‐expert endoscopists, suggesting that this method is useful to diagnose ESCC and determine the resection line

Photoreceptor Cell Apoptosis in the Retinal Degeneration of Uchl3-Deficient Mice

UCH-L3 belongs to the ubiquitin C-terminal hydrolase family that deubiquitinates ubiquitin-protein conjugates in the ubiquitin-proteasome system. A murine Uchl3 deletion mutant displays retinal degeneration, muscular degeneration, and mild growth retardation. To elucidate the function of UCH-L3, we investigated histopathological changes and expression of apoptosis- and oxidative stress-related proteins during retinal degeneration. In the normal retina, UCH-L3 was enriched in the photoreceptor inner segment that contains abundant mitochondria. Although the retina of Uchl3-deficient mice showed no significant morphological abnormalities during retinal development, prominent retinal degeneration became manifested after 3 weeks of age associated with photoreceptor cell apoptosis. Ultrastructurally, a decreased area of mitochondrial cristae and vacuolar changes were observed in the degenerated inner segment. Increased immunoreactivities for manganese superoxide dismutase, cytochrome c oxidase I, and apoptosis-inducing factor in the inner segment indicated mitochondrial oxidative stress. Expression of cytochrome c, caspase-1, and cleaved caspase-3 did not differ between wild-type and mutant mice; however, immunoreactivity for endonuclease G was found in the photoreceptor nuclei in the mutant retina. Hence, loss of UCH-L3 leads to mitochondrial oxidative stress-related photoreceptor cell apoptosis in a caspase-independent manner. Thus, Uchl3-deficient mice represent a model for adult-onset retinal degeneration associated with mitochondrial impairment