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Qazi, M. A., Vora, P., Venugopal, C., McFarlane, N., Subapanditha, M. K., Murty, N. K., et al. (2016). A novel stem cell culture model of recurrent glioblastoma. J Neurooncol, 126(1), 57–67.
Abstract: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults with average disease relapse at 9 months and median survival rarely extending beyond 15 months. Brain tumor stem cells (BTSCs) have been implicated in not only initiating GBM but also conferring resistance to therapy. However, it is not clear whether the BTSC population that initiates tumor growth is also responsible for GBM recurrence. In this study, we have developed a novel in vitro treatment model to profile the evolution of primary treatment-naive GBM BTSCs through chemoradiotherapy. We report that our in vitro model enriched for a CD15+/CD133- BTSC population, mirroring the phenotype of BTSCs in recurrent GBM. We also show that in vitro treatment increased stem cell gene expression as well as self-renewal capacity of primary GBMs. In addition, the chemoradiotherapy-refractory gene signature obtained from gene expression profiling identified a hyper-aggressive subtype of glioma. The delivery of in vitro chemoradiotherapy to primary GBM BTSCs models several aspects of recurrent GBM biology, and could be used as a discovery and drug-screening platform to uncover new biological drivers and therapeutic targets in GBM.
Keywords: Aged; Aged, 80 and over; Analysis of Variance; Antigens, CD/metabolism; Antinematodal Agents/pharmacology; Antineoplastic Agents/pharmacology; Brain Neoplasms/*pathology; Cell Self Renewal/physiology; Dose-Response Relationship, Drug; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic/drug effects/*physiology/radiation effects; Glioblastoma/*pathology; Humans; Male; Middle Aged; Neoplastic Stem Cells/drug effects/*pathology/radiation effects; Polycomb Repressive Complex 1/genetics/metabolism; SOXB1 Transcription Factors/genetics/metabolism; Tumor Cells, Cultured
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Schneider, M., Strobele, S., Nonnenmacher, L., Siegelin, M. D., Tepper, M., Stroh, S., et al. (2016). A paired comparison between glioblastoma “stem cells” and differentiated cells. Int J Cancer, 138(7), 1709–1718.
Abstract: Cancer stem cells (CSC) have been postulated to be responsible for the key features of a malignancy and its maintenances, as well as therapy resistance, while differentiated cells are believed to make up the rapidly growing tumour bulk. It is therefore important to understand the characteristics of those two distinct cell populations in order to devise treatment strategies which effectively target both cohorts, in particular with respect to cancers, such as glioblastoma. Glioblastoma is the most common primary brain tumour in adults, with a mean patient survival of 12-15 months. Importantly, therapeutic improvements have not been forthcoming in the last decade. In this study we compare key features of three pairs of glioblastoma cell populations, each pair consisting of stem cell-like and differentiated cells derived from an individual patient. Our data suggest that while growth rates and expression of key survival- and apoptosis-mediating proteins are more similar according to differentiation status than genetic similarity, we found no intrinsic differences in response to standard therapeutic interventions, namely exposure to radiation or the alkylating agent temozolomide. Interestingly, we could demonstrate that both stem cell-like and differentiated cells possess the ability to form stem cell-containing tumours in immunocompromised mice and that differentiated cells could potentially be dedifferentiated to potential stem cells. Taken together our data suggest that the differences between tumour stem cell and differentiated cell are particular fluent in glioblastoma.
Keywords: Animals; Blotting, Western; Brain Neoplasms/*pathology; Cell Differentiation; DNA Fragmentation; Glioblastoma/*pathology; Heterografts; Humans; Mice; Neoplastic Stem Cells/*pathology; Tumor Cells, Cultured; brain tumour; cancer stem cell; glioblastoma
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Cuppari, L., Nerbass, F. B., Avesani, C. M., & Kamimura, M. A. (2016). A practical approach to dietary interventions for nondialysis-dependent CKD patients: the experience of a reference nephrology center in Brazil. BMC Nephrol, 17(1), 85.
Abstract: This paper describes the 30-year experience on nutritional management of non-dialysis dependent chronic kidney disease (CKD) patients in a public outpatient clinic located in the city of Sao Paulo, Brazil. A team of specialized dietitians in renal nutrition is responsible to provide individual dietary counseling for patients on stages 3 to 5 of CKD. Two different types of nutrition care protocols are employed depending on the level of renal function. For patients with CKD stage 3 a simplified nutritional assessment is performed and the main dietary focus is on the control of protein intake particularly from animal sources. A more complete nutritional assessment as well as a detailed dietary plan focusing not only on the control of protein but also on energy supply and on specific micronutrients is provided for patients on stages 4 or 5 of CKD. Practical approaches and tools used by the dietitians in our clinic for improving patient s adherence to protein, sodium and potassium restriction while maintaining a healthy diet are described in detail in the sections of the article.
Keywords: Brazil; Chronic kidney disease; Diet; Dietary protein
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Cuppari, L., Nerbass, F. B., Avesani, C. M., & Kamimura, M. A. (2016). A practical approach to dietary interventions for nondialysis-dependent CKD patients: the experience of a reference nephrology center in Brazil. BMC Nephrol, 17(1), 85.
Abstract: This paper describes the 30-year experience on nutritional management of non-dialysis dependent chronic kidney disease (CKD) patients in a public outpatient clinic located in the city of Sao Paulo, Brazil. A team of specialized dietitians in renal nutrition is responsible to provide individual dietary counseling for patients on stages 3 to 5 of CKD. Two different types of nutrition care protocols are employed depending on the level of renal function. For patients with CKD stage 3 a simplified nutritional assessment is performed and the main dietary focus is on the control of protein intake particularly from animal sources. A more complete nutritional assessment as well as a detailed dietary plan focusing not only on the control of protein but also on energy supply and on specific micronutrients is provided for patients on stages 4 or 5 of CKD. Practical approaches and tools used by the dietitians in our clinic for improving patient s adherence to protein, sodium and potassium restriction while maintaining a healthy diet are described in detail in the sections of the article.
Keywords: Brazil; Chronic kidney disease; Diet; Dietary protein
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Balbous, A., Cortes, U., Guilloteau, K., Rivet, P., Pinel, B., Duchesne, M., et al. (2016). A radiosensitizing effect of RAD51 inhibition in glioblastoma stem-like cells. BMC Cancer, 16, 604.
Abstract: BACKGROUND: Radioresistant glioblastoma stem cells (GSCs) contribute to tumor recurrence and identification of the molecular targets involved in radioresistance mechanisms is likely to enhance therapeutic efficacy. This study analyzed the DNA damage response following ionizing radiation (IR) in 10 GSC lines derived from patients. METHODS: DNA damage was quantified by Comet assay and DNA repair effectors were assessed by Low Density Array. The effect of RAD51 inhibitor, RI-1, was evaluated by comet and annexin V assays. RESULTS: While all GSC lines displayed efficient DNA repair machinery following ionizing radiation, our results demonstrated heterogeneous responses within two distinct groups showing different intrinsic radioresistance, up to 4Gy for group 1 and up to 8Gy for group 2. Radioresistant cell group 2 (comprising 5 out of 10 GSCs) showed significantly higher RAD51 expression after IR. In these cells, inhibition of RAD51 prevented DNA repair up to 180 min after IR and induced apoptosis. In addition, RAD51 protein expression in glioblastoma seems to be associated with poor progression-free survival. CONCLUSION: These results underscore the importance of RAD51 in radioresistance of GSCs. RAD51 inhibition could be a therapeutic strategy helping to treat a significant number of glioblastoma, in combination with radiotherapy.
Keywords: Comet assay; Glioblastoma stem cells; Rad51; Radioresistance
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