Metabolic status of the human oral mucosa under physiological conditions, upon metabolic stress or following malignant transformation

生理条件下、代谢应激或恶性转化后人类口腔粘膜的代谢状态

• 批准号: 246700238
• 负责人: Professor Dr. Wolfgang Müller-Klieser
• 金额: --
• 依托单位: Klinik für Mund-, Kiefer- und Gesichtschirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/246700238?language=en
• 关键词: Metabolic; status; human; oral; mucosa

The current project is based on the hypothesis that risk factors and co-morbidities, such as the metabolic syndrome, lead to oxidative stress which causes a de-regulation of the carbohydrate metabolism. The resulting so-called Warburg metabolism represents an early and potentially causal event during the development of cancer. Our research will therefore be focused on the metabolic status of human oral mucosa in a normal state, under metabolic stress (by risk factors and co-morbidities) or after malignant transformation. We will characterize glycolysis-related metabolites and proteins, specifically the tissue concentration of ATP, glucose, pyruvate and lactate, as well as the expression level of membrane transporters for cellular glucose uptake (GLUT1/3) and for lactate uptake or excretion (MCT1/4), respectively. The measured parameter values will be correlated with clinical patient data to evaluate their clinical significance. These clinical studies will be supported by cell culture experiments to elucidate molecular mechanisms that underlie the causal link between oxidative stress, Warburg metabolism and malignant transformation. Besides the elucidation of these mechanisms, the ultimate goal of the study is the identification of a set of metabolic parameters which contributes to (i) the improvement of early cancer diagnosis, (ii) the prediction of the degree of malignancy of the disease and (iii) the efficiency of a personalized therapy.

目前的项目是基于这样的假设，即风险因素和合并症，如代谢综合征，导致氧化应激，导致碳水化合物代谢失调。由此产生的所谓的瓦尔堡代谢代表了癌症发展过程中的早期和潜在的因果事件。因此，我们的研究将集中在人类口腔粘膜在正常状态下，在代谢应激（由风险因素和共病）或恶性转化后的代谢状态。我们将表征糖酵解相关代谢物和蛋白质，特别是ATP、葡萄糖、丙酮酸盐和乳酸盐的组织浓度，以及分别用于细胞葡萄糖摄取（GLUT 1/3）和乳酸盐摄取或排泄（MCT 1/4）的膜转运蛋白的表达水平。将测量的参数值与临床患者数据相关联，以评价其临床意义。这些临床研究将得到细胞培养实验的支持，以阐明氧化应激、瓦尔堡代谢和恶性转化之间因果关系的分子机制。除了阐明这些机制外，该研究的最终目标是确定一组代谢参数，这些参数有助于（i）改善早期癌症诊断，（ii）预测疾病的恶性程度和（iii）个性化治疗的效率。

项目成果

Lactate-An Integrative Mirror of Cancer Metabolism.

• DOI: 10.1007/978-3-319-42118-6_2
• 发表时间: 2016
• 期刊: Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer
• 作者: S. Walenta;N. Voelxen;W. Mueller‐Klieser

Lactate as a predictive marker for tumor recurrence in patients with head and neck squamous cell carcinoma (HNSCC) post radiation: a prospective study over 15 years

• DOI: 10.1007/s00784-015-1699-6
• 发表时间: 2016-11-01
• 期刊: CLINICAL ORAL INVESTIGATIONS
• 影响因子: 3.4
• 作者: Blatt, Sebastian;Voelxen, Nadine;Ziebart, Thomas
• 通讯作者: Ziebart, Thomas

Significance of endothelial progenitor cells (EPC) for tumorigenesis of head and neck squamous cell carcinoma (HNSCC): possible marker of tumor progression and neovascularization?

内皮祖细胞（EPC）对头颈鳞状细胞癌（HNSCC）肿瘤发生的意义：肿瘤进展和新血管形成的可能标志物？

• DOI: 10.1007/s00784-016-1785-4
• 发表时间: 2016
• 期刊: Clinical Oral Investigations
• 影响因子: 3.4
• 作者: Ziebart T;Blatt S;Günther C;Völxen N;Pabst A;Sagheb K;Kühl S;Lambrecht T
• 通讯作者: Lambrecht T

Comparative metabolic analysis in head and neck cancer and the normal gingiva

• DOI: 10.1007/s00784-017-2185-0
• 发表时间: 2018-03
• 期刊: Clinical Oral Investigations
• 影响因子: 3.4
• 作者: N. Voelxen;S. Blatt;Pascal Knopf;M. Henkel;Chris Appelhans;L. Righesso;A. Pabst;J. Goldschmitt;S. Walenta;A. Neff;W. Mueller‐Klieser;T. Ziebart