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Goffart, N., Lombard, A., Lallemand, F., Kroonen, J., Nassen, J., Di Valentin, E., et al. (2017). CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone. Neuro Oncol, 19(1), 66–77.
Abstract: BACKGROUND: Patients with glioblastoma (GBM) have an overall median survival of 15 months despite multimodal therapy. These catastrophic survival rates are to be correlated to systematic relapses that might arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. In this line, it has recently been demonstrated that GSCs are able to escape the tumor mass and preferentially colonize the adult subventricular zone (SVZ). At a distance from the initial tumor site, these GSCs might therefore represent a high-quality model of clinical resilience to therapy and cancer relapses as they specifically retain tumor-initiating abilities. METHOD: While relying on recent findings that have validated the existence of GSCs in the human SVZ, we questioned the role of the SVZ niche as a potential GSC reservoir involved in therapeutic failure. RESULTS: Our results demonstrate that (i) GSCs located in the SVZ are specifically resistant to radiation in vivo, (ii) these cells display enhanced mesenchymal roots that are known to be associated with cancer radioresistance, (iii) these mesenchymal traits are specifically upregulated by CXCL12 (stromal cell-derived factor-1) both in vitro and in the SVZ environment, (iv) the amount of SVZ-released CXCL12 mediates GBM resistance to radiation in vitro, and (v) interferes with the CXCL12/CXCR4 signalling system, allowing weakening of the tumor mesenchymal roots and radiosensitizing SVZ-nested GBM cells. CONCLUSION: Together, these data provide evidence on how the adult SVZ environment, through the release of CXCL12, supports GBM therapeutic failure and potential tumor relapse.
Keywords: Animals; Brain Neoplasms/metabolism/*pathology/radiotherapy; Chemokine CXCL12/*metabolism; Cranial Irradiation/*adverse effects; Gamma Rays/adverse effects; Glioblastoma/metabolism/*pathology/radiotherapy; Humans; Lateral Ventricles/metabolism/*pathology/radiation effects; Mice; Mice, Nude; Neoplastic Stem Cells/metabolism/*pathology/radiation effects; *Radiation Tolerance; Signal Transduction/radiation effects; Tumor Cells, Cultured; Cxcl12; glioblastoma; mesenchymal activation; radioresistance; subventricular zone
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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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Fernandez Palacios, L., Barrientos Augustinus, E., Raudales Urquia, C., Frontela Saseta, C., & Ros Berruezo, G. (2017). Degree of malnutrition and its relationship with major structural and eating factors in Honduran preschool population. Prevalence of breastfeeding. Nutr Hosp, 34(3), 639–646.
Abstract: Introduction: Child malnutrition remains a serious public health problem in Honduras, with a national prevalence according to the World Health Organization (WHO) reference values of 29% in children under fi ve. In addition, the average chronic malnutrition in the region amounts to 80% in poor and indigenous communities, making Honduras the second country in Central America with the highest incidence of chronic malnutrition. Another problem of the region is the early cessation of exclusive breastfeeding: only 29.7% of children were exclusively breastfed until they were six months. Therefore, the study seeks to understand, identify and quantify the situation determinants and provide information for the design of public policies. Material and method:: The study consisted of a cross-sectional descriptive anthropometric assessment in which the nutritional status and the prevalence of undernourishment, malnutrition and malnutrition in 141 children aged between six months and fi ve years, belonging to urban and rural regions of the country, were analyzed, as well as assessing the prevalence of breastfeeding in fi ve Honduran departments (Intibuca, Lempira, Atlantida, Olancho and Francisco Morazan). Results and conclusion: When making the analysis by departments, differences regarding nutritional status and breastfeeding were observed between urban and rural areas, the latter being doubled in the case of chronic malnutrition and underweight, with percentages of 14.6% in urban areas versus28.8% in rural areas, and 4.6% in urban areas compared to 9% in rural areas, respectively. However, with respect to acute malnutrition and overweight in both regions, similar values were observed, above 1.1% for acute and 14% for overweight malnutrition. In relation to exclusive breastfeeding for six months, the departments of Olancho and Lempira maintained it for two years, with a percentage distribution of 80% and 48%, respectively. It must be noted that 36% of mothers did not provide breastfeeding, with the highest rate (15%) in the department of Francisco Morazan.
Keywords: *Honduras; *Child malnutrition; *Breastfeeding
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Fernandez Palacios, L., Barrientos Augustinus, E., Raudales Urquia, C., Frontela Saseta, C., & Ros Berruezo, G. (2017). Degree of malnutrition and its relationship with major structural and eating factors in Honduran preschool population. Prevalence of breastfeeding. Nutr Hosp, 34(3), 639–646.
Abstract: Introduction: Child malnutrition remains a serious public health problem in Honduras, with a national prevalence according to the World Health Organization (WHO) reference values of 29% in children under fi ve. In addition, the average chronic malnutrition in the region amounts to 80% in poor and indigenous communities, making Honduras the second country in Central America with the highest incidence of chronic malnutrition. Another problem of the region is the early cessation of exclusive breastfeeding: only 29.7% of children were exclusively breastfed until they were six months. Therefore, the study seeks to understand, identify and quantify the situation determinants and provide information for the design of public policies. Material and method:: The study consisted of a cross-sectional descriptive anthropometric assessment in which the nutritional status and the prevalence of undernourishment, malnutrition and malnutrition in 141 children aged between six months and fi ve years, belonging to urban and rural regions of the country, were analyzed, as well as assessing the prevalence of breastfeeding in fi ve Honduran departments (Intibuca, Lempira, Atlantida, Olancho and Francisco Morazan). Results and conclusion: When making the analysis by departments, differences regarding nutritional status and breastfeeding were observed between urban and rural areas, the latter being doubled in the case of chronic malnutrition and underweight, with percentages of 14.6% in urban areas versus28.8% in rural areas, and 4.6% in urban areas compared to 9% in rural areas, respectively. However, with respect to acute malnutrition and overweight in both regions, similar values were observed, above 1.1% for acute and 14% for overweight malnutrition. In relation to exclusive breastfeeding for six months, the departments of Olancho and Lempira maintained it for two years, with a percentage distribution of 80% and 48%, respectively. It must be noted that 36% of mothers did not provide breastfeeding, with the highest rate (15%) in the department of Francisco Morazan.
Keywords: *Honduras; *Child malnutrition; *Breastfeeding
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Fernandez Palacios, L., Barrientos Augustinus, E., Raudales Urquia, C., Frontela Saseta, C., & Ros Berruezo, G. (2017). Degree of malnutrition and its relationship with major structural and eating factors in Honduran preschool population. Prevalence of breastfeeding. Nutr Hosp, 34(3), 639–646.
Abstract: Introduction: Child malnutrition remains a serious public health problem in Honduras, with a national prevalence according to the World Health Organization (WHO) reference values of 29% in children under fi ve. In addition, the average chronic malnutrition in the region amounts to 80% in poor and indigenous communities, making Honduras the second country in Central America with the highest incidence of chronic malnutrition. Another problem of the region is the early cessation of exclusive breastfeeding: only 29.7% of children were exclusively breastfed until they were six months. Therefore, the study seeks to understand, identify and quantify the situation determinants and provide information for the design of public policies. Material and method:: The study consisted of a cross-sectional descriptive anthropometric assessment in which the nutritional status and the prevalence of undernourishment, malnutrition and malnutrition in 141 children aged between six months and fi ve years, belonging to urban and rural regions of the country, were analyzed, as well as assessing the prevalence of breastfeeding in fi ve Honduran departments (Intibuca, Lempira, Atlantida, Olancho and Francisco Morazan). Results and conclusion: When making the analysis by departments, differences regarding nutritional status and breastfeeding were observed between urban and rural areas, the latter being doubled in the case of chronic malnutrition and underweight, with percentages of 14.6% in urban areas versus28.8% in rural areas, and 4.6% in urban areas compared to 9% in rural areas, respectively. However, with respect to acute malnutrition and overweight in both regions, similar values were observed, above 1.1% for acute and 14% for overweight malnutrition. In relation to exclusive breastfeeding for six months, the departments of Olancho and Lempira maintained it for two years, with a percentage distribution of 80% and 48%, respectively. It must be noted that 36% of mothers did not provide breastfeeding, with the highest rate (15%) in the department of Francisco Morazan.
Keywords: *Honduras; *Child malnutrition; *Breastfeeding
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