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Yanagita, Kengo,Nagashio, Ryo,Ryuge, Shinichiro,Katono, Ken,Jiang, Shi-Xu,Tsuchiya, Benio,Nakashima, Hiroyasu,Fukuda, Eriko,Goshima, Naoki,Saegusa, Makoto,Satoh, Yukitoshi,Masuda, Noriyuki,Sato, Yuich Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.17
Background: Identification of predictive markers for the efficacy of platinum-based chemotherapy is necessary to improve the quality of the life of cancer patients. Materials and Methods: We detected proteins recognized by autoantibodies in pretreated sera from patients with lung adenocarcinoma (AC) evaluated as showing progressive disease (PD) or a partial response (PR) after cisplatin-based chemotherapy by proteomic analysis. Then, the levels of the candidate autoantibodies in the pretreated serum were validated by dot-blot analysis for 22 AC patients who received platinum-based chemotherapy, and the expression of identified proteins was immunohistochemically analyzed in 40 AC biopsy specimens. Results: An autoantibody against galectin-3 (Gal-3) was detected in pretreated sera from an AC patient with PD. Serum IgG levels of anti-Gal-3 autoantibody were significantly higher in patients evaluated with PD than in those with PR and stable disease (SD) (p = 0.0084). Furthermore, pretreated biopsy specimens taken from patients evaluated as showing PD following platinumbased chemotherapy showed a tendency to have a higher positive rate of Gal-3 than those with PR and SD (p = 0.0601). Conclusions: These results suggest that serum IgG levels of anti-Gal-3 autoantibody may be useful to predict the efficacy of platinum-based chemotherapy for patients with lung AC.
S100A16 is a Prognostic Marker for Lung Adenocarcinomas
Saito, Keita,Kobayashi, Makoto,Nagashio, Ryo,Ryuge, Shinichiro,Katono, Ken,Nakashima, Hiroyasu,Tsuchiya, Benio,Jiang, Shi-Xu,Saegusa, Makoto,Satoh, Yukitoshi,Masuda, Noriyuki,Sato, Yuichi Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16
Background: Many functional molecules controlling diverse cellular function are included in low-molecular weight proteins and peptides. Materials and Methods: To identify proteins controlling function in lung adenocarcinomas (AC), we performed two-dimensional gel electrophoresis employing tricine-SDS polyacrylamide in the second dimension (tricine 2-DE). This system was able to detect proteins under 1 kDa even with post-translational modifications. To confirm the utility of detected proteins as novel tumor markers for AC, we performed immunohistochemical analysis using 170 formalin-fixed and paraffin-embedded lung AC tissues. Results: Tricine 2-DE revealed that five proteins including S100A16 were overexpressed in lung AC-derived cells compared with lung squamous cell carcinoma, small cell carcinoma, and large cell neuroendocrine carcinoma-derived cells. Immunohistochemically, S100A16 showed various subcellular localization in lung cancer tissues and a membranous staining status was correlated with the T-factor (P=0.0008), pathological stage (P=0.0015), differentiation extent (P=0.0001), lymphatic invasion (P=0.0007), vascular invasion (P=0.0001), pleural invasion (P=0.0087), and gender (P=0.039), but not with the age or smoking history. More importantly, membranous staining of S100A16 was significantly correlated with a poorer overall survival of either stage I (P=0.0088) or stage II / III (P=0.0003) lung AC patients, and multivariate analysis confirmed that membranous expression of S100A16 was an independent adverse prognostic indicator (P=0.0001). Conclusions: The present results suggest that S100A16 protein is a novel prognostic marker for lung AC.
Serum Periplakin as a Potential Biomarker for Urothelial Carcinoma of the Urinary Bladder
Matsumoto, Kazumasa,Ikeda, Masaomi,Matsumoto, Toshihide,Nagashio, Ryo,Nishimori, Takanori,Tomonaga, Takeshi,Nomura, Fumio,Sato, Yuichi,Kitasato, Hidero,Iwamura, Masatsugu Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22
The objectives of this study were to examine serum periplakin expression in patients with urothelial carcinoma of the urinary bladder and in normal controls, and to examine relationships with clinicopathological findings. Detection of serum periplakin was performed in 50 patients and 30 normal controls with anti-periplakin antibodies using the automatic dot blot system, and a micro-dot blot array with a 256 solid-pin system. Levels in patients with urothelial carcinoma of the urinary bladder were significantly lower than those in normal controls (0.31 and 5.68, respectively; p<0.0001). The area under the receiver-operator curve level for urothelial carcinoma of the urinary bladder was 0.845. The sensitivity and specificity, using a cut-off point of 4.045, were 83.7% and 73.3%, respectively. In addition, serum periplakin levels were significantly higher in patients with muscle-invasive cancer than in those with nonmuscle-invasive cancer (P = 0.03). In multivariate Cox proportional hazards regression analysis, none of the clinicopathological factors was associated with an increased risk for progression and cancer-specific survival. Examination of the serum periplakin level may play a role as a non-invasive diagnostic modality to aid urine cytology and cystoscopy.
Clinicopathological Significance of S100A10 Expression in Lung Adenocarcinomas
Katono, Ken,Sato, Yuichi,Jiang, Shi-Xu,Kobayashi, Makoto,Saito, Keita,Nagashio, Ryo,Ryuge, Shinichiro,Satoh, Yukitoshi,Saegusa, Makoto,Masuda, Noriyuki Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.1
Background: S100A10, of the S100 protein family, is reported to be involved in cancer cell invasion and metastasis. The aims of the present study were to immunohistochemically examine S100A10 expression in surgically resected lung adenocarcinomas, and evaluate any relationships with clinicopathological parameters and prognosis of patients. Materials and Methods: S100A10 expression was immunohistochemically studied in 202 consecutive resected lung adenocarcinomas, and its associations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of S100A10 expression on survival. Results: S100A10 expression was detected in 65 of the 202 (32.2%) lung adenocarcinomas, being significantly correlated with poorer differentiation (P =0.015), a higher pathological TNM stage (stages II and III) (P=0.004), more frequent and severe intratumoral vascular invasion (P=0.001), and a poorer prognosis (P=0.030). However, S100A10 expression was not an independent predictor of survival after controlling for clinicopathological factors. Conclusions: The present study reveals that S100A10 is expressed in a subset of lung adenocarcinomas, and this is related to some clinicopathological parameters, although further studies are required to confirm the correlation between S100A10 expression and prognosis of lung adenocarcinoma patients.
Tsumura, Hideyasu,Matsumoto, Kazumasa,Ikeda, Masaomi,Yanagita, Kengo,Hirano, Shuhei,Hagiwara, Masahiro,Nagashio, Ryo,Fujita, Tetsuo,Sato, Yuichi,Iwamura, Masatsugu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.4
Background: Uroplakins have been widely investigated as potential markers in patients with bladder cancer because these proteins are specific to the urothelium. However, the role of uroplakin proteins in bladder cancer remains unknown. In this study, preoperative serum levels of uroplakin III were measured in patients with urothelial carcinoma of the urinary bladder and examined for possible association with clinicopathological features and clinical outcomes. Materials and Methods: This study included 52 bladder cancer patients at various stages and 28 healthy controls. Uroplakin III levels were detected in preoperative sera using an automated dot blot system and a micro-dot blot array. Results: There was a significant increase in serum uroplakin III levels in patients with bladder cancer as compared to healthy controls (p<0.05). In addition, serum uroplakin III levels were associated with muscle-invasive status, high grade and lymphovascular invasion (p<0.02). Log-rank tests indicated high serum uroplakin III to be significantly associated with cancer-specific mortality. Conclusions: Determination of serum uroplakin III level could be valuable for identifying patients with biologically aggressive bladder cancer.