RESUMO
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.
Assuntos
3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/metabolismo , Carcinoma de Células Escamosas/enzimologia , Complexo Cetoglutarato Desidrogenase/metabolismo , Neoplasias Bucais/enzimologia , Complexo Piruvato Desidrogenase/metabolismo , Tiamina/metabolismo , Western Blotting , Carcinogênese/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Transcetolase/metabolismoRESUMO
OBJECTIVE: To describe the frequency, pattern, and mechanism of windsurfing injuries. METHODS: A 24-question multiple-choice paper-based survey was distributed to windsurfers at beaches in the United States and the Dominican Republic, and an identical survey was placed on the Internet. RESULTS: Two hundred ninety-four surveys in all were completed describing 339 acute and 150 chronic injuries. The foot, knee, chest wall, and ankle were the most commonly injured body parts. Sprains (26.3%) were most common, followed by lacerations (21.2%), contusions (16.2%), and fractures (14.2%). Direct injury from the windsurfing apparatus resulted in 64.5% of the acute injuries, and 12% were caused by contact with the ocean floor. The maneuvers most likely to result in injury were jumping, high-speed falls, and catapult falls. There was no statistically significant difference between the Internet- and paper-based surveys regarding anatomic distribution of injuries or type of injury. The incidence of injuries requiring medical care in study participants was estimated to be one injury per 1000 days sailed. CONCLUSIONS: Sprains, lacerations, and contusions to the lower extremity are the most common windsurfing injuries. Equipment modifications are suggested that may decrease the risk of injury.