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Targeting thiamine-dependent enzymes for metabolic therapies in oral squamous cell carcinoma?
Grimm, M; Calgéer, B; Teriete, P; Biegner, T; Munz, A; Reinert, S.
Afiliação
  • Grimm M; Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstrasse 2-8, 72076, Tuebingen, Germany. dr.dr.martingrimm@googlemail.com.
  • Calgéer B; Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstrasse 2-8, 72076, Tuebingen, Germany.
  • Teriete P; Cancer Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.
  • Biegner T; Department of Pathology, University Hospital Tuebingen, Liebermeisterstrasse 8, 72076, Tuebingen, Germany.
  • Munz A; Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstrasse 2-8, 72076, Tuebingen, Germany.
  • Reinert S; Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstrasse 2-8, 72076, Tuebingen, Germany.
Clin Transl Oncol ; 18(2): 196-205, 2016 Feb.
Article em En | MEDLINE | ID: mdl-26179749
PURPOSE: Thiamine-dependent enzymes (TDEs) linking glycolysis with the tricarboxylic acid cycle (TCA) pyruvate dehydrogenase (PDH), of the pentose phosphate pathway transketolases (TKTs), the TCA alpha-ketoglutarate deydrogenase (KGDH)/2-oxoglutarate dehydrogenase (OGDH) complex, and the amino acid catabolism branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex are crucial factors for tumor metabolism. The expression of these enzymes has not been analyzed for carcinogenesis of oral squamous cell carcinoma (OSCC) with special focus on new targeted metabolic therapies as yet. METHODS: TDEs PDH, KGDH (OGDH), and BCKDH were analyzed in normal oral mucosa (n = 14), oral precursor lesions (simple hyperplasia, n = 21; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 46) by immunohistochemistry and western blot (WB) analysis in OSCC tumor cell lines. RESULTS: Although the total numbers of PDH and KGDH (OGDH) positive samples decreased in OSCC, both enzymes were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue. BCKDH has been demonstrated to be significantly overexpressed in the carcinogenesis of OSCC. Specificity of the antibodies was confirmed by WB analysis. CONCLUSIONS: This is the first study showing increased expression of TDEs in OSCC. Metabolic targeting of TDEs (including TKTs) by antagonistic compounds like oxythiamine or oxybenfothiamine may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Complexo Piruvato Desidrogenase / Tiamina / Neoplasias Bucais / Carcinoma de Células Escamosas / 3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida) / Complexo Cetoglutarato Desidrogenase Limite: Female / Humans / Male Idioma: En Revista: Clin Transl Oncol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Itália
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Complexo Piruvato Desidrogenase / Tiamina / Neoplasias Bucais / Carcinoma de Células Escamosas / 3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida) / Complexo Cetoglutarato Desidrogenase Limite: Female / Humans / Male Idioma: En Revista: Clin Transl Oncol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Itália