br Materials and methods br Results br Discussion The previo

Materials and methods
Results
Discussion The previous studies have reported that positive GLUT1 expression had a predictive value for prognosis of lung cancer patients (Younes et al. 1997a; Meijer et al., 2012; Sasaki et al., 2012). Our conclusion was accordant with these studies. Recently, a meta-analysis has reported that GLUT1 expression was related to poor prognosis in different solid tumors, including breast carcinoma (Younes et al., 1995), oral squamous cell carcinoma (Ayala et al., 2010), and hypopharyngeal carcinoma (Mineta et al., 2002). Interestingly, the significant difference of GLUT1 expression was found between the lung squamous cell carcinoma and adenocarcinoma. Meijer and her colleagues demonstrated that GLUT1 expression is significantly lower in lung adenocarcinoma relative to squamous cell carcinoma, which is consistent with our results (Meijer et al., 2012). These results suggested that the lung adenocarcinoma and squamous cell carcinoma might present the different metabolism. This previous study also suggested that squamous cell carcinoma mainly relies on the mitochondrial while the adenocarcinomas are probably more dependent on the aerobic glycolysis. As shown in the result, GLUT1 was also involved in the progression of lung cancer including the tumor grow, lymph node metastasis, and distant metastasis, differentiation and tumor stage. It is characterized that the cancer N,N-Dimethylsphingosine australia shift the ATP generation relying on the GLUT1 activity (Cairns et al., 2011). The recent study also showed that GLUT1 could regulate the expression of MT1-MMP/MMP2, resulting in the invasion and metastasis of cancer (Xu et al., 2012). It is reported that TNF-α could possibly induce the necrosis and inhibit the tumor growth in vascular-rich tumors, increasing hypoxia in tumor tissues and up-regulating the expression of GLUT-1 (Joost and Thorens, 2001). GLUT-1 may be one of the hypoxia-responsive genes (HRGs) that are directly regulated by TNF-α. Increasing TNF-α activity under hypoxic conditions in the tumor may activate GLUT-1 transcription and enhance glucose transport for the rapid growth of tumor (Hayashi et al., 2004).
Conclusions
Conflict of interest statement
Introduction Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a metabolic encephalopathy caused by a decreased glucose transport into the brain. GLUT1DS was first described in 1991 by De Vivo et al. in two patients with drug-resistant epilepsy, global developmental delay, movement disorder and acquired microcephaly. Since then, the clinical spectrum has expanded to include ataxia, spasticity, chorea, cerebellar tremor, paroxysmal movement disorders and intellectual impairment in varied severity.2, 3 Mutations in the SLC2A1 gene encoding GLUT1 are causative, as a defect in GLUT1 disables the transportation of glucose over the blood–brain barrier. This results in low levels of glucose in the cerebrospinal fluid, i.e. hypoglycorrhachia. Thus, hypoglycorrhachia together with normal blood glucose levels provides the diagnostic clue for GLUT1DS. In 90% of the affected patients, the diagnosis can be confirmed by mutational analysis of the SLC2A1 gene. To date, more than 100 different mutations in the SLC2A1 gene have been identified. Epilepsy is a key feature of the disorder in 85–90% of the affected individuals, with seizure onset generally before the age of two. Many seizure types have been linked to GLUT1DS, including generalized tonic-clonic, absence, focal with and without impaired awareness, myoclonic, atonic, tonic and infantile spasms.7, 8 The majority of patients has more than one seizure type, with generalized tonic-clonic and absence seizures reported most frequently. Epilepsy in GLUT1DS is generally drug-resistant; ketogenic diet (KD) therapy is the mainstay of therapy, as production of ketones provides the brain with an alternative energy source, bypassing the defect in GLUT1.2, 6, 9, 10 KD therapy markedly reduces seizure frequency with reported success percentages ranging from 67 to 90% for complete seizure control, and 80–100% for significant seizure reduction.6, 8, 9, 10, 11 Failure of KD therapy and risk factors for failure have been sparsely published. Hence, we performed a retrospective study of GLUT1DS patients failing on KD therapy, to identify their clinical characteristics.