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Author |
Spencer, D.A.; Auffinger, B.M.; Murphy, J.P.; Muroski, M.E.; Qiao, J.; Gorind, Y.; Lesniak, M.S. |
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Title |
Hitting a Moving Target: Glioma Stem Cells Demand New Approaches in Glioblastoma Therapy |
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Journal Article |
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Year |
2017 |
Publication |
Current Cancer Drug Targets |
Abbreviated Journal |
Curr Cancer Drug Targets |
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Volume |
17 |
Issue |
3 |
Pages |
236-254 |
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Keywords |
Brain Neoplasms/drug therapy/pathology; Drug Resistance, Neoplasm/drug effects; Glioblastoma/*drug therapy/pathology; Glioma/drug therapy/*pathology; Humans; Molecular Targeted Therapy/*methods; Neoplastic Stem Cells/drug effects/*pathology/radiation effects; Chemotherapy; drug targets; glioblastoma multiforme; glioma stem cells; niches; recurrence; resistance |
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Abstract |
BACKGROUND: Glioblastoma multiforme (GBM) continues to devastate patients and outfox investigators and clinicians despite the preponderance of research directed at its biology, pathogenesis and therapeutic advances. GBM routinely outlasts multidisciplinary treatment protocols, almost inevitably recurring in a yet more aggressive and resistant form with distinct genetic differences from the original tumor. Attempts to glean further insight into GBM point increasingly toward a subpopulation of cells with a stem-like phenotype. These cancer stem cells, similar to those now described in a variety of malignancies, are capable of tumorigenesis from a population of susceptible cells. CONCLUSIONS: Glioma stem cells have thus become a prevalent focus in GBM research for their presumed role in development, maintenance and recurrence of tumors. Glioma stem cells infiltrate the white matter surrounding tumors and often evade resection. They are uniquely suited both biochemically and environmentally to resist the best therapy currently available, intrinsically and efficiently resistant to standard chemo- and radiotherapy. These stem cells create an extremely heterogenous tumor that to date has had an answer for every therapeutic question, with continued dismal patient survival. Targeting this population of glioma stem cells may hold the long-awaited key to durable therapeutic efficacy in GBM. |
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Neuro-Oncology Laboratory, Department of Neurosurgery, Northwestern University, 676 N. St. Clair Street, Suite 2210, Chicago, IL60611, United States |
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1568-0096 |
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PMID:27993114 |
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Call Number |
ref @ user @ |
Serial |
96616 |
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Author |
de Morais Sato, P.; Unsain, R.F.; Gittelsohn, J.; Sanches Tavares da Silva, J.G.; Goncalves Perez, I.C.; Baeza Scagliusi, F. |
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Title |
Strategies used by overweight and obese low-income mothers to feed their families in urban Brazil |
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Journal Article |
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Year |
2017 |
Publication |
Appetite |
Abbreviated Journal |
Appetite |
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Volume |
111 |
Issue |
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Pages |
63-70 |
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Keywords |
Brazil; Food insecurity; Low-income; Obesity; Overweight; Women |
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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. |
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Department of Nutrition, School of Public Health, University of Sao Paulo, Av. Dr. Arnaldo, 715 – Sao Paulo/SP – CEP 01255-000, Sao Paulo/SP, Brazil |
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0195-6663 |
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PMID:28034737 |
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ref @ user @ |
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97449 |
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Author |
de Morais Sato, P.; Unsain, R.F.; Gittelsohn, J.; Sanches Tavares da Silva, J.G.; Goncalves Perez, I.C.; Baeza Scagliusi, F. |
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Title |
Strategies used by overweight and obese low-income mothers to feed their families in urban Brazil |
Type |
Journal Article |
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Year |
2017 |
Publication |
Appetite |
Abbreviated Journal |
Appetite |
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Volume |
111 |
Issue |
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Pages |
63-70 |
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Keywords |
Brazil; Food insecurity; Low-income; Obesity; Overweight; Women |
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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. |
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Department of Nutrition, School of Public Health, University of Sao Paulo, Av. Dr. Arnaldo, 715 – Sao Paulo/SP – CEP 01255-000, Sao Paulo/SP, Brazil |
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0195-6663 |
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PMID:28034737 |
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Call Number |
ref @ user @ |
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98033 |
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Author |
Hira, V.V.V.; Verbovsek, U.; Breznik, B.; Srdic, M.; Novinec, M.; Kakar, H.; Wormer, J.; der Swaan, B.V.; Lenarcic, B.; Juliano, L.; Mehta, S.; Van Noorden, C.J.F.; Lah, T.T. |
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Title |
Cathepsin K cleavage of SDF-1alpha inhibits its chemotactic activity towards glioblastoma stem-like cells |
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Journal Article |
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Year |
2017 |
Publication |
Biochimica et Biophysica Acta |
Abbreviated Journal |
Biochim Biophys Acta |
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Volume |
1864 |
Issue |
3 |
Pages |
594-603 |
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Keywords |
Amino Acid Sequence; Cathepsin K/genetics/*metabolism; Cell Line, Tumor; Chemokine CXCL12/chemistry/genetics/*metabolism; Chemotaxis; Gene Expression; Heterocyclic Compounds/pharmacology; Humans; Neoplastic Stem Cells/*metabolism/pathology; Neuroglia/*metabolism/pathology; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Proteolysis; Receptors, CXCR/genetics/metabolism; Receptors, CXCR4/antagonists & inhibitors/genetics/*metabolism; Stem Cell Niche/genetics; *Cathepsin K; *Glioma stem-like cells; *Niche; *Stromal-derived factor-1alpha |
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Abstract |
Glioblastoma (GBM) is the most aggressive primary brain tumor with poor patient survival that is at least partly caused by malignant and therapy-resistant glioma stem-like cells (GSLCs) that are protected in GSLC niches. Previously, we have shown that the chemo-attractant stromal-derived factor-1alpha (SDF-1alpha), its C-X-C receptor type 4 (CXCR4) and the cysteine protease cathepsin K (CatK) are localized in GSLC niches in glioblastoma. Here, we investigated whether SDF-1alpha is a niche factor that through its interactions with CXCR4 and/or its second receptor CXCR7 on GSLCs facilitates their homing to niches. Furthermore, we aimed to prove that SDF-1alpha cleavage by CatK inactivates SDF-1alpha and inhibits the invasion of GSLCs. We performed mass spectrometric analysis of cleavage products of SDF-1alpha after proteolysis by CatK. We demonstrated that CatK cleaves SDF-1alpha at 3 sites in the N-terminus, which is the region of SDF-1alpha that binds to its receptors. Confocal imaging of human GBM tissue sections confirmed co-localization of SDF-1alpha and CatK in GSLC niches. In accordance, 2D and 3D invasion experiments using CXCR4/CXCR7-expressing GSLCs and GBM cells showed that SDF-1alpha had chemotactic activity whereas CatK cleavage products of SDF-1alpha did not. Besides, CXCR4 inhibitor plerixafor inhibited invasion of CXCR4/CXCR7-expressing GSLCs. In conclusion, CatK can cleave and inactivate SDF-1alpha. This implies that CatK activity facilitates migration of GSLCs out of niches. We propose that activation of CatK may be a promising strategy to prevent homing of GSLCs in niches and thus render these cells sensitive to chemotherapy and radiation. |
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Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Vecna pot 111, 1000 Ljubljana, Slovenia; Jozef Stefan International Postgraduate School, Jamova 39, 1000 Ljubljana, Slovenia; Department of Biochemistry, Faculty of Chemistry and Chemical Engineering, University of Ljubljana, Vecna pot 113, 1000 Ljubljana, Slovenia |
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0006-3002 |
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PMID:28040478 |
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Call Number |
ref @ user @ |
Serial |
96615 |
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Author |
Lee, J.W.; Lim, D.H.; Sung, K.W.; Lee, H.J.; Yi, E.S.; Yoo, K.H.; Koo, H.H.; Suh, Y.L.; Shin, H.J. |
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Title |
Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents |
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Journal Article |
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Year |
2017 |
Publication |
Journal of Korean Medical Science |
Abbreviated Journal |
J Korean Med Sci |
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Volume |
32 |
Issue |
2 |
Pages |
195-203 |
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Keywords |
Adolescent; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use; Brain Neoplasms/*drug therapy/mortality/therapy; Carboplatin/administration & dosage; Child; Child, Preschool; Etoposide/administration & dosage; Female; Glioma/*drug therapy/mortality/therapy; Humans; Male; Neoplasm Grading; Remission Induction; Retrospective Studies; Stem Cell Transplantation; Survival Rate; Thiotepa/administration & dosage; Transplantation, Autologous; Treatment Outcome; *Autologous Stem Cell Transplantation; *Brain Tumor; *Children; *High-dose Chemotherapy; *High-grade Glioma |
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Abstract |
With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% +/- 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT. |
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Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. shinhj@skku.edu |
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1011-8934 |
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Notes |
PMID:28049229 |
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Call Number |
ref @ user @ |
Serial |
96614 |
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