| Records |
| Author |
Alshehri, M.M.; Robbins, S.M.; Senger, D.L. |
| Title |
The Role of Neurotrophin Signaling in Gliomagenesis: A Focus on the p75 Neurotrophin Receptor (p75NTR/CD271) |
Type |
Journal Article |
| Year |
2017 |
Publication |
Vitamins and Hormones |
Abbreviated Journal |
Vitam Horm |
| Volume |
104 |
Issue |
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Pages |
367-404 |
| Keywords |
Brain tumor; Cd271; Cancer stem cells; Glioblastoma; Glioma invasion; Nerve growth factor; Neurotrophin; p75(NTR) |
| Abstract |
The p75 neurotrophin receptor (p75NTR, a.k.a. CD271), a transmembrane glycoprotein and a member of the tumor necrosis family (TNF) of receptors, was originally identified as a nerve growth factor receptor in the mid-1980s. While p75NTR is recognized to have important roles during neural development, its presence in both neural and nonneural tissues clearly supports the potential to mediate a broad range of functions depending on cellular context. Using an unbiased in vivo selection paradigm for genes underlying the invasive behavior of glioma, a critical characteristic that contributes to poor clinical outcome for glioma patients, we identified p75NTR as a central regulator of glioma invasion. Herein we review the expanding role that p75NTR plays in glioma progression with an emphasis on how p75NTR may contribute to the treatment refractory nature of glioma. Based on the observation that p75NTR is expressed and functional in two critical glioma disease reservoirs, namely, the highly infiltrative cells that evade surgical resection, and the radiation- and chemotherapy-resistant brain tumor-initiating cells (also referred to as brain tumor stem cells), we propose that p75NTR and its myriad of downstream signaling effectors represent rationale therapeutic targets for this devastating disease. Lastly, we provide the provocative hypothesis that, in addition to the well-documented cell autonomous signaling functions, the neurotrophins, and their respective receptors, contribute in a cell nonautonomous manner to drive the complex cellular and molecular composition of the brain tumor microenvironment, an environment that fuels tumorigenesis. |
Address  |
Arnie Charbonneau Cancer Centre, University of Calgary, Calgary, AB, Canada. Electronic address: senger@ucalgary.ca |
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English |
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Edition |
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| ISSN |
0083-6729 |
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| Notes |
PMID:28215302 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96606 |
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| Author |
Roh, T.H.; Park, H.H.; Kang, S.-G.; Moon, J.H.; Kim, E.H.; Hong, C.-K.; Ahn, S.S.; Choi, H.J.; Cho, J.; Kim, S.H.; Lee, S.K.; Kim, D.S.; Kim, S.H.; Suh, C.-O.; Lee, K.S.; Chang, J.H. |
| Title |
Long-term outcomes of concomitant chemoradiotherapy with temozolomide for newly diagnosed glioblastoma patients: A single-center analysis |
Type |
Journal Article |
| Year |
2017 |
Publication |
Medicine |
Abbreviated Journal |
Medicine (Baltimore) |
| Volume |
96 |
Issue |
27 |
Pages |
e7422 |
| Keywords |
Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating/*therapeutic use; Brain Neoplasms/diagnosis/genetics/metabolism/*therapy; *Chemoradiotherapy; DNA Methylation; DNA Modification Methylases/genetics/metabolism; DNA Repair Enzymes/genetics/metabolism; Dacarbazine/*analogs & derivatives/therapeutic use; Disease-Free Survival; Female; Follow-Up Studies; Glioblastoma/diagnosis/genetics/metabolism/*therapy; Humans; Male; Middle Aged; Prognosis; Promoter Regions, Genetic; Retrospective Studies; Treatment Outcome; Tumor Suppressor Proteins/genetics/metabolism; Young Adult |
| Abstract |
The present study analyzed outcomes of surgery followed by concomitant chemoradiotherapy (CCRT) with temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM) at a single institution. Outcomes were retrospectively reviewed in 252 consecutive patients with newly diagnosed GBM who underwent surgery followed by CCRT with TMZ at the authors' institution between 2005 and 2013. At initial operation, 126 (50.0%), 55 (21.8%), 45 (17.9%), and 26 (10.3%) patients underwent gross total resection (GTR), subtotal resection, partial resection (PR), and biopsy, respectively. Their median overall survival (OS) was 20.8 months (95% confidence interval [CI] 17.7-23.9 months) and their median progression-free survival was 12.7 months (95% CI 11.2-14.2 months). The O-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 78 (34.1%) of the 229 patients assayed, and an isocitrate dehydrogenase 1 mutation was detected in 7 (6.6%) of the 106 patients analyzed. Univariate analyses showed that patient age, involvement of eloquent areas, involvement of the subventricular zone, presence of leptomeningeal seeding, Karnofsky Performance Status, extent of resection (EOR), MGMT promoter methylation, and presence of an oligodendroglioma component were prognostic of OS. Multivariate analysis showed that age, involvement of eloquent areas, presence of leptomeningeal seeding, EOR, and MGMT promoter methylation were significantly predictive of survival. OS in patients with GBM who undergo surgery followed by CCRT with TMZ is enhanced by complete resection. Other factors significantly prognostic of OS include that age, involvement of eloquent areas, presence of leptomeningeal seeding, and MGMT promoter methylation. |
| Address |
aYonsei University Graduate School, Seoul bDepartment of Neurosurgery, Ajou University Hospital, Ajou University School of Medicine, Suwon cDepartment of Neurosurgery dDepartment of Radiology eDepartment of Medical Oncology fDepartment of Radiation Oncology gDepartment of Pathology, Yonsei University College of Medicine hBrain Tumor Center, Severance Hospital, Yonsei University Health System iBrain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea |
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English |
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0025-7974 |
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| Notes |
PMID:28682902 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96578 |
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| Author |
Heffernan, J.M.; McNamara, J.B.; Borwege, S.; Vernon, B.L.; Sanai, N.; Mehta, S.; Sirianni, R.W. |
| Title |
PNIPAAm-co-Jeffamine(R) (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells |
Type |
Journal Article |
| Year |
2017 |
Publication |
Biomaterials |
Abbreviated Journal |
Biomaterials |
| Volume |
143 |
Issue |
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Pages |
149-158 |
| Keywords |
Brain tumor initiating cells; Cancer stem cells; Radioresistance; Temperature responsive polymer scaffolds; Tissue engineering |
| Abstract |
Glioblastoma (GBM) is the most common adult primary brain tumor, and the 5-year survival rate is less than 5%. GBM malignancy is driven in part by a population of GBM stem-like cells (GSCs) that exhibit indefinite self-renewal capacity, multipotent differentiation, expression of neural stem cell markers, and resistance to conventional treatments. GSCs are enriched in specialized niche microenvironments that regulate stem phenotypes and support GSC radioresistance. Therefore, identifying GSC-niche interactions that regulate stem phenotypes may present a unique target for disrupting the maintenance and persistence of this treatment resistant population. In this work, we engineered 3D scaffolds from temperature responsive poly(N-isopropylacrylamide-co-Jeffamine M-1000(R) acrylamide), or PNJ copolymers, as a platform for enriching stem-specific phenotypes in two molecularly distinct human patient-derived GSC cell lines. Notably, we observed that, compared to conventional neurosphere cultures, PNJ cultured GSCs maintained multipotency and exhibited enhanced self-renewal capacity. Concurrent increases in expression of proteins known to regulate self-renewal, invasion, and stem maintenance in GSCs (NESTIN, EGFR, CD44) suggest that PNJ scaffolds effectively enrich the GSC population. We further observed that PNJ cultured GSCs exhibited increased resistance to radiation treatment compared to GSCs cultured in standard neurosphere conditions. GSC radioresistance is supported in vivo by niche microenvironments, and this remains a significant barrier to effectively treating these highly tumorigenic cells. Taken in sum, these data indicate that the microenvironment created by synthetic PNJ scaffolds models niche enrichment of GSCs in patient-derived GBM cell lines, and presents tissue engineering opportunities for studying clinically important behaviors such as radioresistance in vitro. |
| Address |
Barrow Brain Tumor Research Center, Barrow Neurological Institute, 350 W Thomas Ave, Phoenix, AZ, 85013, USA; School of Biological and Health Systems Engineering, Arizona State University, PO Box 879709, Tempe, AZ, 85287, USA. Electronic address: rachael.sirianni@dignityhealth.org |
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English |
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0142-9612 |
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| Notes |
PMID:28802102 |
Approved |
no |
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ref @ user @ |
Serial |
96570 |
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| Author |
McCloskey, M.L.; Tarazona-Meza, C.E.; Jones-Smith, J.C.; Miele, C.H.; Gilman, R.H.; Bernabe-Ortiz, A.; Miranda, J.J.; Checkley, W. |
| Title |
Disparities in dietary intake and physical activity patterns across the urbanization divide in the Peruvian Andes |
Type |
Journal Article |
| Year |
2017 |
Publication |
The International Journal of Behavioral Nutrition and Physical Activity |
Abbreviated Journal |
Int J Behav Nutr Phys Act |
| Volume |
14 |
Issue |
1 |
Pages |
90 |
| Keywords |
24-h recall; Chronic diseases; Low- and middle income countries; Nutrition transition; Overweight; Urbanization |
| Abstract |
BACKGROUND: Diet and activity are thought to worsen with urbanization, thereby increasing risk of obesity and chronic diseases. A better understanding of dietary and activity patterns across the urbanization divide may help identify pathways, and therefore intervention targets, leading to the epidemic of overweight seen in low- and middle-income populations. Therefore, we sought to characterize diet and activity in a population-based study of urban and rural residents in Puno, Peru. METHODS: We compared diet and activity in 1005 (503 urban, 502 rural) participants via a lifestyle questionnaire. We then recruited an age- and sex-stratified random sample of 50 (25 urban, 25 rural) participants to further characterize diet and activity. Among these participants, diet composition and macronutrient intake was assessed by three non-consecutive 24-h dietary recalls and physical activity was assessed using Omron JH-720itc pedometers. RESULTS: Among 1005 participants, we found that urban residents consumed protein-rich foods, refined grains, sugary items, and fresh produce more frequently than rural residents. Among the 50 subsample participants, urban dwellers consumed more protein (47 vs. 39 g; p = 0.05), more carbohydrates (280 vs. 220 g; p = 0.03), more sugary foods (98 vs. 48 g, p = 0.02) and had greater dietary diversity (6.4 vs 5.8; p = 0.04). Rural subsample participants consumed more added salt (3.1 vs 1.7 g, p = 0.006) and tended to consume more vegetable oil. As estimated by pedometers, urban subsample participants burned fewer calories per day (191 vs 270 kcal, p = 0.03). CONCLUSIONS: Although urbanization is typically thought to increase consumption of fat, sugar and salt, our 24-h recall results were mixed and showed lower levels of obesity in rural Puno were not necessarily indicative of nutritionally-balanced diets. All subsample participants had relatively traditional lifestyles (low fat intake, limited consumption of processed foods and frequent walking) that may play a role in chronic disease outcomes in this region. |
| Address |
Biomedical Research Unit, A.B. PRISMA, Lima, Peru. wcheckl1@jhmi.edu |
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English |
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Series Issue |
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1479-5868 |
ISBN |
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Expedition |
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Conference |
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| Notes |
PMID:28693514 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
97446 |
| Permanent link to this record |
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| Author |
McCloskey, M.L.; Tarazona-Meza, C.E.; Jones-Smith, J.C.; Miele, C.H.; Gilman, R.H.; Bernabe-Ortiz, A.; Miranda, J.J.; Checkley, W. |
| Title |
Disparities in dietary intake and physical activity patterns across the urbanization divide in the Peruvian Andes |
Type |
Journal Article |
| Year |
2017 |
Publication |
The International Journal of Behavioral Nutrition and Physical Activity |
Abbreviated Journal |
Int J Behav Nutr Phys Act |
| Volume |
14 |
Issue |
1 |
Pages |
90 |
| Keywords |
24-h recall; Chronic diseases; Low- and middle income countries; Nutrition transition; Overweight; Urbanization |
| Abstract |
BACKGROUND: Diet and activity are thought to worsen with urbanization, thereby increasing risk of obesity and chronic diseases. A better understanding of dietary and activity patterns across the urbanization divide may help identify pathways, and therefore intervention targets, leading to the epidemic of overweight seen in low- and middle-income populations. Therefore, we sought to characterize diet and activity in a population-based study of urban and rural residents in Puno, Peru. METHODS: We compared diet and activity in 1005 (503 urban, 502 rural) participants via a lifestyle questionnaire. We then recruited an age- and sex-stratified random sample of 50 (25 urban, 25 rural) participants to further characterize diet and activity. Among these participants, diet composition and macronutrient intake was assessed by three non-consecutive 24-h dietary recalls and physical activity was assessed using Omron JH-720itc pedometers. RESULTS: Among 1005 participants, we found that urban residents consumed protein-rich foods, refined grains, sugary items, and fresh produce more frequently than rural residents. Among the 50 subsample participants, urban dwellers consumed more protein (47 vs. 39 g; p = 0.05), more carbohydrates (280 vs. 220 g; p = 0.03), more sugary foods (98 vs. 48 g, p = 0.02) and had greater dietary diversity (6.4 vs 5.8; p = 0.04). Rural subsample participants consumed more added salt (3.1 vs 1.7 g, p = 0.006) and tended to consume more vegetable oil. As estimated by pedometers, urban subsample participants burned fewer calories per day (191 vs 270 kcal, p = 0.03). CONCLUSIONS: Although urbanization is typically thought to increase consumption of fat, sugar and salt, our 24-h recall results were mixed and showed lower levels of obesity in rural Puno were not necessarily indicative of nutritionally-balanced diets. All subsample participants had relatively traditional lifestyles (low fat intake, limited consumption of processed foods and frequent walking) that may play a role in chronic disease outcomes in this region. |
| Address |
Biomedical Research Unit, A.B. PRISMA, Lima, Peru. wcheckl1@jhmi.edu |
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English |
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Abbreviated Series Title |
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1479-5868 |
ISBN |
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| Notes |
PMID:28693514 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
97634 |
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