Repressing malic enzyme 1 redirects glucose metabolism,unbalances the redox state,and attenuates migratory and invasive abilities in nasopharyngeal carcinoma cell lines

A large amount of nicotinamide adenine dinucleotide phosphate(NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells.Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool.ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis.In the present study,we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells.High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells.However,there were no obvious changes in the other two pathways for glucose metabolism:glycolysis and oxidative phosphorylation.Interestingly,NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells,whereas no significant difference was observed under high-glucose condition.ME1-repressed cells had significantly decreased tolerance to low-glucose condition.Moreover,NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress.Furthermore,diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein.Collectively,these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.

Temozolomide chemotherapy based on MGMT protein expression for patients with malignant gliomas:a report of 40 cases

Objective This study is to evaluate the efficacy and toxicity of temozolomide (TMZ) chemotherapy based on O 6 -methylguanine-DNA methyltransferase (MGMT) protein expression in patients with malignant gliomas. Methods A total of 40 patients with pathologically confirmed malignant gliomas were enrolled. All patients had pretreated with radiotherapy and had assessable lesions.

Nature：研究鉴定出侵袭性胰腺癌细胞及其弱点

在一项新的研究中，来自美国德州大学MD安德森癌症中心的研究人员利用患者源性肿瘤异种移植（patient—derived tumorxenograft,PDx）和模式小鼠开展一系列临床前实验，鉴定出一种门卫蛋白（gatekee Perprotein）阻止胰腺癌细胞转化为一种极具侵袭性的细胞类型，并且也发现剔除这种门卫蛋白的疗法能够阻止这些癌细胞。这些发现有助为携带这种进展迅速的治疗抵抗性的胰腺癌细胞亚群的患者开发出潜在的疗法。