| Records |
| Author |
Gravina, G.L.; Mancini, A.; Colapietro, A.; Vitale, F.; Vetuschi, A.; Pompili, S.; Rossi, G.; Marampon, F.; Richardson, P.J.; Patient, L.; Patient, L.; Burbidge, S.; Festuccia, C. |
| Title |
The novel CXCR4 antagonist, PRX177561, reduces tumor cell proliferation and accelerates cancer stem cell differentiation in glioblastoma preclinical models |
Type |
Journal Article |
| Year |
2017 |
Publication |
Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine |
Abbreviated Journal |
Tumour Biol |
| Volume |
39 |
Issue |
6 |
Pages  |
1010428317695528 |
| Keywords |
Adult; Animals; Cell Differentiation/drug effects; Cell Line, Tumor; Cell Movement/drug effects; Cell Proliferation/drug effects; Chemokine CXCL12/*genetics; Disease-Free Survival; Glioblastoma/*drug therapy/genetics; Humans; Mice; Neoplasm Recurrence, Local/*drug therapy/genetics/pathology; Neoplastic Stem Cells/drug effects/pathology; Neovascularization, Pathologic/*drug therapy/genetics/pathology; Receptors, CXCR4/antagonists & inhibitors/*genetics; Signal Transduction/drug effects; Tumor Microenvironment/drug effects; Cxcr4; Glioblastoma; angiogenesis; monocyte infiltration |
| Abstract |
Glioblastoma is the most frequent and the most lethal primary brain tumor among adults. Standard of care is the association of radiotherapy with concomitant or adjuvant temozolomide. However, to date, recurrence is inevitable. The CXCL12/CXCR4 pathway is upregulated in the glioblastoma tumor microenvironment regulating tumor cell proliferation, local invasion, angiogenesis, and the efficacy of radio-chemotherapy. In this study, we evaluated the effects of the novel CXCR4 antagonist, PRX177561, in preclinical models of glioblastoma. CXCR4 expression and PRX177561 effects were assessed on a panel of 12 human glioblastoma cells lines and 5 patient-derived glioblastoma stem cell cultures. Next, the effect of PRX177561 was tested in vivo, using subcutaneous injection of U87MG, U251, and T98G cells as well as orthotopic intrabrain inoculation of luciferase-transfected U87MG cells. Here we found that PRX177561 impairs the proliferation of human glioblastoma cell lines, increases apoptosis, and reduces CXCR4 expression and cell migration in response to stromal cell-derived factor 1alpha in vitro. PRX177561 reduced the expression of stem cell markers and increased that of E-cadherin and glial fibrillary acidic protein in U87MG cells consistent with a reduction in cancer stem cells. In vivo, PRX177561 reduced the weight and increased the time to progression of glioblastoma subcutaneous tumors while increasing disease-free survival and overall survival of mice bearing orthotopic tumors. Our findings suggest that targeting stromal cell-derived factor 1 alpha/CXCR4 axis by PRX177561 might represent a novel therapeutic approach against glioblastoma and support further investigation of this compound in more complex preclinical settings in order to determine its therapeutic potential. |
| Address |
1 Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, L'Aquila, Italy |
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English |
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1010-4283 |
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| Notes |
PMID:28639900 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96581 |
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| Author |
de Sousa, J.F.; Torrieri, R.; Serafim, R.B.; Di Cristofaro, L.F.M.; Escanfella, F.D.; Ribeiro, R.; Zanette, D.L.; Paco-Larson, M.L.; da Silva, W.A.J.; Tirapelli, D.P. da C.; Neder, L.; Carlotti, C.G.J.; Valente, V. |
| Title |
Expression signatures of DNA repair genes correlate with survival prognosis of astrocytoma patients |
Type |
Journal Article |
| Year |
2017 |
Publication |
Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine |
Abbreviated Journal |
Tumour Biol |
| Volume |
39 |
Issue |
4 |
Pages |
1010428317694552 |
| Keywords |
Apoptosis; Astrocytoma/genetics/metabolism/*mortality; Brain Neoplasms/genetics/metabolism/*mortality; Cell Cycle; Cell Line, Tumor; *DNA Repair; DNA Repair Enzymes/genetics/metabolism; Exodeoxyribonucleases/genetics/metabolism; Gene Expression; Humans; Kaplan-Meier Estimate; N-Glycosyl Hydrolases/genetics/metabolism; Prognosis; DNA repair; astrocytoma; genomic instability; glioblastoma; tumor progression |
| Abstract |
Astrocytomas are the most common primary brain tumors. They are very resistant to therapies and usually progress rapidly to high-grade lesions. Here, we investigated the potential role of DNA repair genes in astrocytoma progression and resistance. To this aim, we performed a polymerase chain reaction array-based analysis focused on DNA repair genes and searched for correlations between expression patters and survival prognoses. We found 19 genes significantly altered. Combining these genes in all possible arrangements, we found 421 expression signatures strongly associated with poor survival. Importantly, five genes (DDB2, EXO1, NEIL3, BRCA2, and BRIP1) were independently correlated with worse prognoses, revealing single-gene signatures. Moreover, silencing of EXO1, which is remarkably overexpressed, promoted faster restoration of double-strand breaks, while NEIL3 knockdown, also highly overexpressed, caused an increment in DNA damage and cell death after irradiation of glioblastoma cells. These results disclose the importance of DNA repair pathways for the maintenance of genomic stability of high-grade astrocytomas and suggest that EXO1 and NEIL3 overexpression confers more efficiency for double-strand break repair and resistance to reactive oxygen species, respectively. Thereby, we highlight these two genes as potentially related with tumor aggressiveness and promising candidates as novel therapeutic targets. |
| Address |
7 Center for Integrative Systems Biology (CISBi), NAP/USP, Ribeirao Preto, Brazil |
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1010-4283 |
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| Notes |
PMID:28378638 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96598 |
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| Author |
Bischof, J.; Westhoff, M.-A.; Wagner, J.E.; Halatsch, M.-E.; Trentmann, S.; Knippschild, U.; Wirtz, C.R.; Burster, T. |
| Title |
Cancer stem cells: The potential role of autophagy, proteolysis, and cathepsins in glioblastoma stem cells |
Type |
Journal Article |
| Year |
2017 |
Publication |
Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine |
Abbreviated Journal |
Tumour Biol |
| Volume |
39 |
Issue |
3 |
Pages |
1010428317692227 |
| Keywords |
Animals; Autophagy; Brain Neoplasms/*metabolism/*pathology; Cathepsins/*metabolism; Glioblastoma/*metabolism/*pathology; Humans; Neoplastic Stem Cells/*metabolism/*pathology; Proteolysis; *Major histocompatibility complex class I; *autophagy; *cathepsin; *glioblastoma |
| Abstract |
One major obstacle in cancer therapy is chemoresistance leading to tumor recurrence and metastasis. Cancer stem cells, in particular glioblastoma stem cells, are highly resistant to chemotherapy, radiation, and immune recognition. In case of immune recognition, several survival mechanisms including, regulation of autophagy, proteases, and cell surface major histocompatibility complex class I molecules, are found in glioblastoma stem cells. In different pathways, cathepsins play a crucial role in processing functional proteins that are necessary for several processes and proper cell function. Consequently, strategies targeting these pathways in glioblastoma stem cells are promising approaches to interfere with tumor cell survival and will be discussed in this review. |
| Address |
3 Department of Neurosurgery, Surgery Center, Ulm University Medical Center, Ulm University, Ulm, Germany |
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English |
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1010-4283 |
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| Notes |
PMID:28347245 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96600 |
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| Author |
Mello, A. de C.; Carvalho, M.S.; Alves, L.C.; Gomes, V.P.; Engstrom, E.M. |
| Title |
[Food consumption and anthropometry related to the frailty syndrome in low-income community-living elderly in a large city] |
Type |
Journal Article |
| Year |
2017 |
Publication |
Cadernos de Saude Publica |
Abbreviated Journal |
Cad Saude Publica |
| Volume |
33 |
Issue |
8 |
Pages |
e00188815 |
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Aged; Aged, 80 and over; *Anthropometry; Brazil; Cross-Sectional Studies; Female; *Food; Frail Elderly/*statistics & numerical data; Geriatric Assessment; Humans; Male; Middle Aged; Nutrition Assessment; Nutrition Surveys; Socioeconomic Factors |
| Abstract |
The aim of this study was to describe anthropometric and food intake data related to the frailty syndrome in the elderly. This was a cross-sectional study in individuals >/= 60 years of age in a household survey in the Manguinhos neighborhood of Rio de Janeiro, Brazil (n = 137). Frailty syndrome was diagnosed according to Fried et al., anthropometric measures were taken, and a food frequency questionnaire was applied and the results compared to Brazilian Ministry of Health guidelines. In the pre-frail and frail groups, body mass index and measures of central adiposity showed higher levels, while lean muscle parameters showed lower values, proportional to the syndrome's gradation. Frail elderly consumed higher amounts of grains and lower amounts of beans and fruit; pre-frail elderly consumed more vegetables, dairy products, and high-sugar and high-fat foods; the two groups consumed similar amounts of meat. Thus, diagnosis of the syndrome, anthropometric evaluation, and dietary assessment should be included in health policies for the elderly, since they assist in early identification of risk and favor interventions for disease prevention and health and nutritional promotion. |
| Address |
Escola Nacional de Saude Publica Sergio Arouca, Fundacao Oswaldo Cruz, Rio de Janeiro, Brasil |
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Portuguese |
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Consumo alimentar e antropometria relacionados a sindrome de fragilidade em idosos residentes em comunidade de baixa renda de um grande centro urbano |
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0102-311X |
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| Notes |
PMID:28832786 |
Approved |
no |
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ref @ user @ |
Serial |
98007 |
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| Author |
Ferrari, T.K.; Cesar, C.L.G.; Alves, M.C.G.P.; Barros, M.B. de A.; Goldbaum, M.; Fisberg, R.M. |
| Title |
[Healthy lifestyle in Sao Paulo, Brazil] |
Type |
Journal Article |
| Year |
2017 |
Publication |
Cadernos de Saude Publica |
Abbreviated Journal |
Cad Saude Publica |
| Volume |
33 |
Issue |
1 |
Pages |
e00188015 |
| Keywords |
Adolescent; Adult; Aged; Alcoholism/*epidemiology; Brazil/epidemiology; Child; Cross-Sectional Studies; *Exercise; *Feeding Behavior; Female; *Healthy Lifestyle; Humans; Male; Middle Aged; Smoking/*epidemiology; Socioeconomic Factors; Young Adult |
| Abstract |
The objective was to analyze adolescent, adult, and elderly lifestyles in the city of Sao Paulo, Brazil, according to demographic and socioeconomic variables. A cross-sectional, population-based study was performed with data from the Health Survey in Sao Paulo City (ISA-Capital 2008) database. Lifestyle was defined on the basis of physical activity, diet, smoking, and alcohol abuse and addiction, according to the respective guidelines. Prevalence of healthy lifestyle was 36.9% in the elderly, 15.4% in adults, and 9.8% in adolescents, and was higher in females in the elderly and adults. Among individuals with unhealthy lifestyle, 51.5% of the elderly, 32.2% of adults, and 57.9% of adolescents failed to reach the guidelines for adequate diet. Prevalence of healthy lifestyle was highest among the elderly, followed by adults and adolescents. Food consumption was the main factor associated with unhealthy lifestyle, demonstrating the importance of interventions to promote healthy lifestyle, especially adequate diet. |
| Address |
Faculdade de Saude Publica, Universidade de Sao Paulo, Sao Paulo, Brasil |
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Portuguese |
Summary Language |
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Original Title |
Estilo de vida saudavel em Sao Paulo, Brasil |
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0102-311X |
ISBN |
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| Notes |
PMID:28125129 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
98028 |
| Permanent link to this record |
