Diagnostic value of peptidome analyses for protease activated pathological conditions beyond cancer diagnosis

肽组分析对癌症诊断之外的蛋白酶激活病理状况的诊断价值

• 批准号: 19390156
• 负责人: HASHIGUCHI Teruto
• 金额: $ 12.4万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19390156/
• 关键词: プロテオーム; ペプチドーム; ペプチド; バイオマーカー; 質量分析; 癌; DIC; 検査; 酵素; 生体分子; 蛋白質; peptidome; proteome; peptide; biomarker; inflammation; cancer; diagnosis; degradome; MOF

Human serum contains thousands of proteolytically derived low-molecular-weight peptide fragments (serum peptidome). The concept of utilizing the serum peptidome for cancer diagnosis has been developed. A pathological serum peptidome appears when the homeostatic balance between proteases and protease inhibitors is disrupted. We hypothesize if analyses of the serum peptidome are of diagnostic value as information on which molecules are disrupted, and the pathological course it will take in unknown pathological conditions and disseminated intravascular coagulation (DIC). We analyzed the serum peptidome in 3 stages (early stage, pre-DIC and DIC stages) in one patient with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes) syndrome, an intractable disease with unknown pathology, using a 1-dimensional gel electrophoresis/ matrix-assisted laser desorption/ionization-mass spectrometry (1-DE/MS)-based rapid quantitative approach. A very large number of peptide fragments appeared in the DIC stage, compared to pre-DIC. In addition, we identified fragments of transthyretin (ALGISPFHEHAEVVFTANDSGPR, m/z 2,451.18) and α1-antitrypsin (EDPQGDAAQKTDTSHHDQDHPTFN, m/z 2,691.02) that significantly increased in the DIC stage, compared to those in the pre-DIC stage. Rapid analyses of the serum peptidome may lead to a diagnostic method that can predict on-going protease activated pathological conditions and help to decide on multilateral strategies including nutritional support and drug therapy.

人血清包含数千种蛋白水解衍生的低分子量肽片段（血清肽）。已经开发了使用血清肽进行癌症诊断的概念。当禁用蛋白酶和蛋白酶抑制剂之间的稳态平衡时，就会出现病理血清肽。我们假设对血清肽的分析是否具有诊断价值，因为这些分子被破坏的信息，并且它将在未知的病理条件下进行的病理学病程和散布的血管内凝结（DIC）。我们分析了一名诗歌（多神经病，有机肿大，内分泌病，M蛋白质和皮肤变化）的患者的三个阶段（早期，前序和DIC阶段）的血清辣味，这是一种使用一维病理学的顽固性疾病，是一种顽固性疾病（1-DE/MS）基于快速定量方法。与DIC阶段相比，DIC阶段出现了大量的肽片段。此外，我们确定了经胸蛋白（algispfhehaevvftAndsgpr，m/z 2,451.18）和α1-抗抗胰蛋白酶（EDPQGDAAQKTDTSHHDQDHDQDHPTPTFN，M/z 2,691.02）的片段，与DIC相比，这些阶段大大增加了。快速分析血清辣妹可能会导致一种诊断方法，该方法可以预测持续的蛋白酶激活的病理状况，并有助于决定包括营养支持和药物治疗在内的多边策略。

项目成果

The diagnostic value of endothelial function as a potential sensor of fatigue in health.

• DOI: 10.2147/vhrm.s8950
• 发表时间: 2010-03-24
• 期刊: Vascular health and risk management
• 影响因子: 2.9
• 作者: Ohno Y;Hashiguchi T;Maenosono R;Yamashita H;Taira Y;Minowa K;Yamashita Y;Kato Y;Kawahara K;Maruyama I
• 通讯作者: Maruyama I

Diagnostic value of serum peptidome analyses for protease activated pathological conditions beyond cancer diagnosis

血清肽组分析对癌症诊断之外的蛋白酶激活病理状况的诊断价值

• 发表时间: 2009
• 期刊: Med Hypotheses 73
• 作者: Hashiguchi T;Tanaka K;et al.
• 通讯作者: et al.

Degradation of non-hemostatic molecules in DIC/MOF

DIC/MOF 中非止血分子的降解

• 发表时间: 2008
• 作者: 竹本圭;黒沢カルメン;濱西誠司;柴森雅文;高木二郎;瀧川智子;王達紘;荻野景規;Hashiguchi T
• 通讯作者: Hashiguchi T

Serum VEGF increases in diabetic polyneuropathy, particularly in the neurologically active symptomatic stage

• DOI: 10.1111/j.1464-5491.2009.02680.x
• 发表时间: 2009-03-01
• 期刊: DIABETIC MEDICINE
• 影响因子: 3.5
• 作者: Deguchi, T.;Hashiguchi, T.;Arimura, K.
• 通讯作者: Arimura, K.

新規癌マーカーおよびそれを用いた診断

新的癌症标记物和使用它们的诊断

• 发表时间: 2009