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Ludwig, K., & Kornblum, H. I. (2017). Molecular markers in glioma. J Neurooncol, .
Abstract: Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas.
Keywords: Glioblastoma; Glioma stem cell; Molecular markers; Mutations; Pathways
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Munthe, S., Halle, B., Boldt, H. B., Christiansen, H., Schmidt, S., Kaimal, V., et al. (2017). Shift of microRNA profile upon glioma cell migration using patient-derived spheroids and serum-free conditions. J Neurooncol, 132(1), 45–54.
Abstract: Glioblastoma multiforme (GBM) is the most frequent malignant primary brain tumor. A major reason for the overall median survival being only 14.6 months is migrating tumor cells left behind after surgery. Another major reason is tumor cells having a so-called cancer stem cell phenotype being therefore resistant towards traditional chemo- and radiotherapy. A group of novel molecular targets are microRNAs (miRNAs). MiRNAs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. The aim of this study was to identify differentially expressed miRNAs in migrating GBM cells using serum-free stem cell conditions. We used patient-derived GBM spheroid cultures for a novel serum-free migration assay. MiRNA expression of migrating tumor cells isolated at maximum migration speed was compared with corresponding spheroids using an OpenArray Real-Time PCR System. The miRNA profiling revealed 30 miRNAs to be differentially expressed. In total 13 miRNAs were upregulated and 17 downregulated in migrating cells compared to corresponding spheroids. The three most deregulated miRNAs, miR-1227 (up-regulated), miR-32 (down-regulated) and miR-222 (down-regulated), were experimentally overexpressed. A non-significantly increased migration rate was observed after miR-1227 overexpression. A significantly reduced migration rate was observed after miR-32 and miR-222 overexpression. In conclusion a shift in microRNA profile upon glioma cell migration was identified using an assay avoiding serum-induced migration. Both the miRNA profiling and the functional validation suggested that miR-1227 may be associated with increased migration and miR-32 and miR-222 with decreased migration. These miRNAs may represent potential novel targets in migrating glioma cells.
Keywords: Glioblastoma; MicroRNA; Migration; Serum-free; Target
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Mistry, A. M., Dewan, M. C., White-Dzuro, G. A., Brinson, P. R., Weaver, K. D., Thompson, R. C., et al. (2017). Decreased survival in glioblastomas is specific to contact with the ventricular-subventricular zone, not subgranular zone or corpus callosum. J Neurooncol, 132(2), 341–349.
Abstract: The clinical effect of radiographic contact of glioblastoma (GBM) with neurogenic zones (NZ)-the ventricular-subventricular (VSVZ) and subgranular (SGZ) zones-and the corpus callosum (CC) remains unclear and, in the case of the SGZ, unexplored. We investigated (1) if GBM contact with a NZ correlates with decreased survival; (2) if so, whether this effect is associated with a specific NZ; and (3) if radiographic contact with or invasion of the CC by GBM is associated with decreased survival. We retrospectively identified 207 adult patients who underwent cytoreductive surgery for GBM followed by chemotherapy and/or radiation. Age, preoperative Karnofsky performance status score (KPS), and extent of resection were recorded. Preoperative MRIs were blindly analyzed to calculate tumor volume and assess its contact with VSVZ, SGZ, CC, and cortex. Overall (OS) and progression free (PFS) survivals were calculated and analyzed with multivariate Cox analyses. Among the 207 patients, 111 had GBM contacting VSVZ (VSVZ+GBMs), 23 had SGZ+GBMs, 52 had CC+GBMs, and 164 had cortex+GBMs. VSVZ+, SGZ+, and CC+ GBMs were significantly larger in size relative to their respective non-contacting controls. Multivariate Cox survival analyses revealed GBM contact with the VSVZ, but not SGZ, CC, or cortex, as an independent predictor of lower OS, PFS, and early recurrence. We hypothesize that the VSVZ niche has unique properties that contribute to GBM pathobiology in adults.
Keywords: Glioblastoma; Stem cells; Subgranular zone; Subventricular zone; Survival; Ventricular-subventricular zone
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de Morais Sato, P., Unsain, R. F., Gittelsohn, J., Sanches Tavares da Silva, J. G., Goncalves Perez, I. C., & Baeza Scagliusi, F. (2017). Strategies used by overweight and obese low-income mothers to feed their families in urban Brazil. Appetite, 111, 63–70.
Abstract: OBJECTIVE: To describe and compare strategies adopted by overweight and obese low-income mothers living in different vulnerable contexts to deal with food constraints and feed their families. DESIGN: Qualitative in-depth interviews. Data were analyzed with exploratory content analysis and the number of segments per theme was used to compare neighborhoods. SETTING: Three low-income neighborhoods in Santos, Brazil. PARTICIPANTS: A purposive sample of 21 overweight or obese mothers. RESULTS: We identified three main types of strategies, namely, food acquisition, cooking, and eating. Food acquisition included social support and food-sourcing strategies. Social support strategies ranged from macro (governmental programs) to micro (family) levels. Food-sourcing strategies involved price research and use of credit to buy foods. Cooking approaches included optimizing food (e.g., adding water to beans), avoiding wastefulness, and substitutions (e.g., using water instead of milk when making cakes). Eating themes ranged from lack of quantity to lack of quality. Strategies to deal with the lack of food were affected by family dynamics, such as prioritizing provision of fruits to children. Food choices (e.g., low consumption of fruits and high consumption of fatty meats) derived from strategies may help promote overweight and obesity. Furthermore, for participants, financial constraints were perceived as barriers to following nutritionists' recommendations and weight loss. CONCLUSIONS: This study highlights the barriers that low-income women face in adopting a healthy diet and sheds light on the importance of the symbolic value of food, even in the context of food insecurity. Finally, it suggests that environmental aspects could increase the accessibility to fruits and vegetables. These findings could be used to inform the planning and implementation of interventions.
Keywords: Brazil; Food insecurity; Low-income; Obesity; Overweight; Women
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de Morais Sato, P., Unsain, R. F., Gittelsohn, J., Sanches Tavares da Silva, J. G., Goncalves Perez, I. C., & Baeza Scagliusi, F. (2017). Strategies used by overweight and obese low-income mothers to feed their families in urban Brazil. Appetite, 111, 63–70.
Abstract: OBJECTIVE: To describe and compare strategies adopted by overweight and obese low-income mothers living in different vulnerable contexts to deal with food constraints and feed their families. DESIGN: Qualitative in-depth interviews. Data were analyzed with exploratory content analysis and the number of segments per theme was used to compare neighborhoods. SETTING: Three low-income neighborhoods in Santos, Brazil. PARTICIPANTS: A purposive sample of 21 overweight or obese mothers. RESULTS: We identified three main types of strategies, namely, food acquisition, cooking, and eating. Food acquisition included social support and food-sourcing strategies. Social support strategies ranged from macro (governmental programs) to micro (family) levels. Food-sourcing strategies involved price research and use of credit to buy foods. Cooking approaches included optimizing food (e.g., adding water to beans), avoiding wastefulness, and substitutions (e.g., using water instead of milk when making cakes). Eating themes ranged from lack of quantity to lack of quality. Strategies to deal with the lack of food were affected by family dynamics, such as prioritizing provision of fruits to children. Food choices (e.g., low consumption of fruits and high consumption of fatty meats) derived from strategies may help promote overweight and obesity. Furthermore, for participants, financial constraints were perceived as barriers to following nutritionists' recommendations and weight loss. CONCLUSIONS: This study highlights the barriers that low-income women face in adopting a healthy diet and sheds light on the importance of the symbolic value of food, even in the context of food insecurity. Finally, it suggests that environmental aspects could increase the accessibility to fruits and vegetables. These findings could be used to inform the planning and implementation of interventions.
Keywords: Brazil; Food insecurity; Low-income; Obesity; Overweight; Women
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