A number of studies suggest that cancer stem cells are essential for tumour growth, and failure to target these cells can result in tumour relapse. As this population of cells has been shown to be resistant to radiation and chemotherapy, it is essential to understand their biology and identify new therapeutic approaches. Targeting cancer metabolism is a potential alternative strategy to counteract tumour growth and recurrence. Here we applied a proteomic and targeted metabolomic analysis in order to point out the main metabolic differences between breast cancer cells grown as spheres and thus enriched in cancer stem cells were compared with the same cells grown in adherent differentiating conditions. This integrated approach allowed us to identify a metabolic phenotype associated with the stem-like condition and shows that breast cancer stem cells (BCSCs) shift from mitochondrial oxidative phosphorylation towards fermentative glycolysis. Functional validation of proteomic and metabolic data provide evidences for increased activities of key enzymes of anaerobic glucose fate such as pyruvate kinase M2 isoform, lactate dehydrogenase and glucose 6-phopshate dehydrogenase in cancer stem cells as well as different redox status. Moreover, we show that treatment with 2-deoxyglucose, a well known inhibitor of glycolysis, inhibits BCSC proliferation when used alone and shows a synergic effect when used in combination with doxorubicin. In conclusion, we suggest that inhibition of glycolysis may be a potentially effective strategy to target BCSCs.

Summary:Purpose: To analyze the results of surgical treatment of intractable epilepsy in patients with subcortical band heterotopia, or double cortex syndrome, a diffuse neuronal migration disorder.Methods: We studied eight patients (five women) with double cortex syndrome and intractable epilepsy. All had a comprehensive presurgical evaluation including prolonged video-EEG recordings and magnetic resonance imaging (MRI).Results: All patients had partial seizures, with secondary generalization in six of them. Neurologic examination was normal in all. Three were of normal intelligence, and five were mildly retarded. Six patients underwent invasive EEG recordings, three of them with subdural grids and three with stereotactic implanted depth electrodes (SEEG). Although EEG recordings showed multilobar epileptic abnormalities in most patients, regional or focal seizure onset was recorded in all. MRI showed bilateral subcortical band heterotopia, asymmetric in thickness in three. An additional area of cortical thickening in the left frontal lobe was found in one patient. Surgical procedures included multiple subpial transections in two patients, frontal lesionectomy in one, temporal lobectomy with amygdalohippocampectomy in five, and an additional anterior callosotomy in one. Five patients had no significant improvement, two had some improvement, and one was greatly improved.Conclusion: Our results do not support focal surgical removal of epileptogenic tissue in patients with double cortex syndrome, even in the presence of a relatively localized epileptogenic area.

The ErbB tyrosine kinase receptor family has been shown to have an important role in tumorigenesis, and the expression of its receptor members is frequently deregulated in many types of solid tumors. Various drugs targeting these receptors have been approved for cancer treatment. Particularly, in breast cancer, anti-Her2/EGFR molecules represent the standard therapy for Her2-positive malignancies. However, in a number of cases, the tumor relapses or progresses thus suggesting that not all cancer cells have been targeted. One possibility is that a subset of cells capable of regenerating the tumor, such as cancer stem cells (CSCs), may not respond to these therapeutic agents. Accumulating evidences indicate that miR-205-5p is significantly downregulated in breast tumors compared with normal breast tissue and acts as a tumor suppressor directly targeting oncogenes such as Zeb1 and ErbB3. In this study, we report that miR-205-5p is highly expressed in BCSCs and represses directly ERBB2 and indirectly EGFR leading to resistance to targeted therapy. Furthermore, we show that miR-205-5p directly regulates the expression of p63 which is in turn involved in the EGFR expression suggesting a miR-205/p63/EGFR regulation.

The authors analyzed the CLCN2 chloride channel gene in 112 probands with familial epilepsy, detecting 18 common polymorphisms. Two brothers with generalized epilepsy and their asymptomatic father, and a father and son with focal epilepsy carried variants of possible functional significance that were not found in 192 controls. The authors conclude that CLCN2 mutations may be a rare cause of familial epilepsy. Further studies are needed to test if polymorphisms in this gene are associated with epilepsy.