記述言語：日本語   出版者・発行元：日本電気泳動学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Our aim was to develop a serodiagnostic marker for lung cancer. Monoclonal antibodies were generated, and one antibody designated as KU-Lu-1, recognizing cytoskeleton-associated protein 4 (CKAP4), was studied further. To evaluate the utility of KU-Lu-1 antibody as a serodiagnostic marker for lung cancer, reverse-phase protein array analysis was performed with sera of 271 lung cancer patients and 100 healthy controls. CKAP4 was detected in lung cancer cells and tissues, and its secretion into the culture supernatant was also confirmed. The serum CKAP4 levels of lung cancer patients were significantly higher than those of healthy controls (P < 0.0001), and the area under the curve of receiver-operating characteristic curve analysis was 0.890, with 81.1% sensitivity and 86.0% specificity. Furthermore, the serum CKAP4 levels were also higher in patients with stage I adenocarcinoma or squamous cell carcinoma than in healthy controls (P < 0.0001). Serum CKAP4 levels may differentiate lung cancer patients from healthy controls, and they may be detected early even in stage I non-small cell lung cancer. Serum CKAP4 levels were also significantly higher in lung cancer patients than in healthy controls in the validation set (P < 0.0001). The present results provide evidence that CKAP4 may be a novel early serodiagnostic marker for lung cancer.

DOI： 10.1016/j.ajpath.2018.03.007

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病理学会  

researchmap

掲載種別：研究論文（学術雑誌）  

DOI： 10.2198/electroph.62.9

researchmap

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本電気泳動学会  

<p>肺癌の血清診断マーカーを開発するため表面タンパク質を標識，回収後，shotgun analysisによって同定した．3つの肺癌細胞株の表面タンパク質をビオチン化し，回収した．ビオチン化タンパク質はshotgun analysisによって同定した．4つの組織型の異なる肺癌細胞株と培養上清を用いて同定されたタンパク質の発現レベルを免疫ブロット法および免疫染色法により確認した．さらに，肺癌患者血清（268例）および健常者血清（100例）を用いてreverse-phase protein array法により血清中のCD109レベルを測定した．血清中のCD109レベルは健常者に比して腺癌（AC）および扁平上皮癌（SCC）患者において有意に高値を示した（p < 0.0001）．健常者を対照群，ACとSCC患者を判別群としたReceiver-operating characteristic curve解析を行った結果，Area under the curveは0.93であり，最適カットオフ値を1.13に設定した時，感度は84％，特異度は88％であった．さらに，CD109はstage Iでも検出されたことから，CD109は肺癌の早期血清診断マーカーである可能性が示唆された．</p>

DOI： 10.2198/electroph.61.23

CiNii Article

researchmap

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本電気泳動学会  

<p>肺がんの膜タンパク質に対する新規血清診断マーカーを開発するために，膜タンパク質を様々なプロテオーム法と組み合わせて同定した．肺癌細胞の膜タンパク質をビオチン化し，回収後，ショットガン解析により同定した．組織型の異なる4つの肺癌細胞株を用いて，免疫ブロット法と免疫染色法により同定されたタンパク質の発現を確認した．また，肺癌患者と健常患者血清を用いたReverse-phase protein array法により血清中のタンパク質レベルを測定した．CD109，CD155とRoundabout Guidance Receptor 1を含む92個の膜タンパク質が同定され，本実験ではCD155タンパク質に着目した．血清中のCD155レベルは健常者に比して肺腺癌および肺扁平上皮癌患者で有意に上昇していた（<i>p</i><0.0001）．Receiver-operating characteristic curve解析を行った結果，Area under the curveは0.87であり，cut off値を0.31に設定した場合，感度と特異度はそれぞれ81％と82％であった．この方法は膜タンパク質に対する新規診断マーカーの獲得に有用であることが示された．</p>

DOI： 10.2198/electroph.61.120

CiNii Article

researchmap

掲載種別：研究論文（学術雑誌）  

DOI： 10.2198/electroph.61.39

researchmap

記述言語：日本語   出版者・発行元：日本電気泳動学会  

<p>我々は肺癌組織や細胞，そして患者血清を用い，ランダム免疫法を用いた単クローン性抗体の作製，二次元電気泳動法を用いた解析，そして自己抗体解析など，様々なプロテオミクス手法を駆使して肺癌の組織や血清診断マーカー候補タンパク質の獲得を目指した研究を行ってきた．一方，II–IIIA期の非小細胞性肺癌患者では腫瘍の完全切除後にプラチナ製剤を用いた補助化学療法を行うことが世界的な標準治療法となっている．しかし，その効果は未だ十分とは言えない．現在，この治療法が有効か否かの事前の個別検査は行われていない．今回，我々がこれまで獲得してきた肺癌マーカーについて，術後補助化学療法の効果予測マーカーとしての有用性を検討した．この総説では，nestin，S100A16，myosin-9を中心にその有用性について述べる．さらに，新規の術後補助化学療法の効果予測マーカー獲得の現状についても述べたい．</p>

DOI： 10.2198/electroph.61.128

CiNii Article

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SCIENTIFIC PUBLISHERS INDIA  

To identify diagnostic markers of psoriasis vulgaris and psoriatic arthritis, autoantibodies in sera from patients with psoriasis were screened by two-dimensional immunoblotting (2D-IB). We previously found 22 autoantigens each in psoriasis sera. In this study, serum levels of valosin-containing protein (VCP) in patients, one of the identified autoantigens in psoriasis patients, were studied by reverse-phase protein array analysis using sera from patients with psoriasis and healthy controls. Serum levels of VCP were significantly higher in patients with psoriatic arthritis than in controls or patients with psoriasis vulgaris (P&lt;0.05 each). The area under the curve for VCP between patients with psoriatic arthritis and controls or psoriatic vulgaris patients was 0.88 and 0.77, respectively. The serum level of VCP was weakly correlated with the disease activity of psoriasis patients and psoriasis area severity index score. These data suggest that VCP is a novel and differential sero-diagnostic marker of psoriatic arthritis.

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

To investigate the relationships between the expression of MUC5B and clinicopathological parameters, the expression of MUC5B was immunohistochemically studied. MUC5B expression was observed in 129 of 198 (65.2%) adenocarcinomas and in 4 of 49 (8.2%) squamous cell carcinomas (P < 0.00001). MUC5B expression was significantly associated with poorer differentiation (P = 0.0303), higher pathological TNM stage (p = 0.0153) and poorer prognosis of adenocarcinoma patients (P = 0.0017). Multivariable analysis with Cox proportional hazards models confirmed that MUC5B expression increased the hazard of death after adjusting for other clinicopathological factors (HR = 2.66; 95%CI, 1.26-5.61). We also immunohistochemically evaluated TTF-1 expression and found that the combination of MUC5B with TTF-1 is a useful marker for adenocarcinomas. The diagnostic accuracies of TTF-1 and MUC5B for adenocarcinoma were 83.8% and 70.4%, respectively. The accuracy increased to 94.3% when the two factors were combined. In survival analysis, the MUC5B(High)/TTF-1(-) group was significantly associated with a poorer outcome compared with the MUC5B(Low)/TTF-1(+) group (p < 0.0001). The present study suggested that the combination of MUC5B and TTF-1 expression is useful for discriminating adenocarcinomas from squamous cell carcinomas, yielding prognostic significance in patients with lung adenocarcinoma.

DOI： 10.1038/srep08649

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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 platinum- based 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.

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

PubMed

researchmap

記述言語：日本語   出版者・発行元：Japanese Electrophoresis Society  

DOI： 10.2198/electroph.59.129

CiNii Article

researchmap

その他リンク： https://jlc.jst.go.jp/DN/JLC/20016223408?from=CiNii

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cancer tissues are comprised of various components including tumor cells and the surrounding tumor stroma, which consists of the extracellular matrix and inflammatory cells. Since the tumor stroma plays critical roles in tumor development, investigation of the tumor stroma in addition to tumor cells is important to identify useful tumor-associated markers. To discover novel and useful sero-diagnostic markers, a comparative study of tumor-associated autoantibodies (AAbs) in sera from lung adenocarcinoma (AC) patients was investigated by two-dimensional immunoblotting with AC cell lines or each autologous AC tissues. Autoantigens identified from tissue and cell line samples comprised 58 (45 antigens) and 53 spots (41 antigens), respectively. Thirty-six proteins including Transforming growth factor-beta-induced protein ig-h3 (BIGH3) and Hyaluronan and proteoglycan link protein 1 (HAPLN1) were detected only from tissues, 32 proteins only from cell lines, and 9 proteins from both. BIGH3 and HAPLN1 expressions were confirmed in the tumor stroma, but not in AC cell lines by immunostaining and immunoblotting. These data suggest that autologous tumor tissue and serum are important to coincidently detect AAbs derived from the tumor stroma in addition to tumor cells.

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

To identify diagnostic markers for psoriasis vulgaris and psoriatic arthritis, autoantibodies in sera from psoriasis vulgaris and psoriatic arthritis patients were screened by two-dimensional immunoblotting (2D-IB). Based on 2D-IB and MADLI TOF/TOF-MS analyses, eleven proteins each in psoriasis vulgaris and psoriatic arthritis were identified as autoantigens. Furthermore, serum levels of moesin, keratin 17 (K17), annexin A1 (ANXA1), and stress-induced phophoprotein-1 (STIP1), which were detected as autoantigens, were studied by dot blot analysis with psoriasis patients and healthy controls. The levels of moesin and STIP1 were significantly higher in sera from patients with psoriasis vulgaris than in the controls (moesin: P<0.05, STIP1: P<0.005). The area under the curve (AUC) for moesin and STIP1 between patients with psoraisis vulgaris and controls was 0.747 and 0.792, respectively. STIP1 and K17 levels were significantly higher in sera from patients with psoriatic arthritis than in those with psoriasis vulgaris (P<0.05 each). The AUC for STIP1 and K17 between patients with psoriatic arthritis and psoriasis vulgaris was 0.69 and 0.72, respectively. The STIP1 or moesin, CK17 serum level was not correlated with disease activity of psoriasis patients. These data suggest that STIP1 and moesin may be novel and differential sero-diagnostic markers for psoriasis vulgaris and psoriatic arthritis.

DOI： 10.1371/journal.pone.0101773

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

To investigate the level of serum S100A6 in patients with bladder cancer and in healthy controls and compare these levels with clinicopathologic findings, we evaluated the level of serum S100A6 in 30 healthy controls and 50 patients with bladder cancer diagnosed via transurethral resection of bladder tumor and/or radical cystectomy. S100A6 in sera was detected by employing automatic dot blot systems, and the micro Dot Blot array with a 256-solid pin configuration. The normalized signal of serum S100A6 expression in bladder cancer patients was significantly higher than that of healthy controls (P = 0.001). Serum S100A6 expression of non-muscle-invasive cancer (NMIC) was significantly higher than that of healthy controls (P = 0.04). Furthermore, the S100A6 serum level in patients with muscle-invasive bladder cancer was significantly higher than that in patient with NMIC (P = 0.004). The sensitivity and specificity were 48.0% (95% CI: 0.337-0.626) and 93.3% (95% CI: 0.779-0.992), respectively. The area under the curve was 0.727. Serum S100A6 expression is a potentially effective detection marker for bladder cancer. Applying this serum marker to clinical practice would require less-invasive examinations of patients and would help to detect life-threatening cancerous lesions earlier than current modalities.

DOI： 10.2220/biomedres.35.351

PubMed

researchmap

記述言語：日本語   出版者・発行元：Japanese Electrophoresis Society  

DOI： 10.2198/sbk.58.68

CiNii Article

CiNii Books

researchmap

その他リンク： https://jlc.jst.go.jp/DN/JALC/10040886465?from=CiNii

記述言語：英語   掲載種別：研究論文（学術雑誌）  

To develop sero-diagnostic markers for lung cancer, we generated monoclonal antibodies using pulmonary adenocarcinoma (AD)-derived A549 cells as antigens by employing the random immunization method. Hybridoma supernatants were immunohistochemically screened for antibodies with AMeX-fixed and paraffin-embedded A549 cell preparations. Positive clones were monocloned twice through limiting dilutions. From the obtained monoclonal antibodies, we selected an antibody designated as KU-Lu-5 which showed intense membrane staining of A549 cells. Based on immunoprecipitation and MADLI TOF/TOF-MS analysis, this antibody was recognized as carbonic anhydrase XII (CAXII). To evaluate the utility of this antibody as a sero-diagnostic marker for lung cancer, we performed dot blot analysis with a training set consisting of sera from 70 lung cancer patients and 30 healthy controls. The CAXII expression levels were significantly higher in lung cancer patients than in healthy controls in the training set (P<0.0001), and the area under the curve of ROC was 0.794, with 70.0% specificity and 82.9% sensitivity. In lung cancers, expression levels of CAXII were significantly higher in patients with squamous cell carcinoma (SCC) than with AD (P = 0.035). Furthermore, CAXII was significantly higher in well- and moderately differentiated SCCs than in poorly differentiated ones (P = 0.027). To further confirm the utility of serum CAXII levels as a sero-diagnostic marker, an additional set consisting of sera from 26 lung cancer patients and 30 healthy controls was also investigated by dot blot analysis as a validation study. Serum CAXII levels were also significantly higher in lung cancer patients than in healthy controls in the validation set (P = 0.030). Thus, the serum CAXII levels should be applicable markers discriminating lung cancer patients from healthy controls. To our knowledge, this is the first report providing evidence that CAXII may be a novel sero-diagnostic marker for lung cancer.

DOI： 10.1371/journal.pone.0033952

PubMed

researchmap

記述言語：日本語   出版者・発行元：日本プロテオーム学会（日本ヒトプロテオーム機構）  

DOI： 10.14889/jhupo.2011.0.166.0

CiNii Article

researchmap

記述言語：日本語   出版者・発行元：日本プロテオーム学会（日本ヒトプロテオーム機構）  

DOI： 10.14889/jhupo.2011.0.167.0

CiNii Article

researchmap

記述言語：日本語   出版者・発行元：日本プロテオーム学会（日本ヒトプロテオーム機構）  

DOI： 10.14889/jhupo.2010.0.115.1

CiNii Article

researchmap

開催年月日： 2010年8月

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap