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Bijangi-Vishehsaraei, K.; Reza Saadatzadeh, M.; Wang, H.; Nguyen, A.; Kamocka, M.M.; Cai, W.; Cohen-Gadol, A.A.; Halum, S.L.; Sarkaria, J.N.; Pollok, K.E.; Safa, A.R. |
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Title |
Sulforaphane suppresses the growth of glioblastoma cells, glioblastoma stem cell-like spheroids, and tumor xenografts through multiple cell signaling pathways |
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Journal Article |
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2017 |
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Journal of Neurosurgery |
Abbreviated Journal |
J Neurosurg |
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1-12 |
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CCCP = carbonyl cyanide m-chlorophenylhydrazone; DMSO = dimethyl sulfoxide; DSB = double-strand break; EGF = epidermal growth factor; FACS = fluorescence-activated cell sorting; FGF = fibroblast growth factor; GBM = glioblastoma; GSC = glioblastoma stem cell; IC50 = 50% inhibition of cell survival; MRC = mitochondrial respiratory chain; MSC = mesenchymal stromal cell; NAC = N-acetylcysteine; NSG = nonobese diabetic scid gamma; PE = phycoerythrin; ROS = reactive oxygen species; SFN = sulforaphane; SSB = single-strand break; apoptosis; cancer stem cells; glioblastoma; oncology; sulforaphane |
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OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM. METHODS The inhibitory effects of SFN on established cell lines, early primary cultures, CD133-positive GSCs, GSC-derived spheroids, and GBM xenografts were evaluated using various methods, including GSC isolation and the sphere-forming assay, analysis of reactive oxygen species (ROS) and apoptosis, cell growth inhibition assay, comet assays for assessing SFN-triggered DNA damage, confocal microscopy, Western blot analysis, and the determination of in vivo efficacy as assessed in human GBM xenograft models. RESULTS SFN triggered the significant inhibition of cell survival and induced apoptotic cell death, which was associated with caspase 3 and caspase 7 activation. Moreover, SFN triggered the formation of mitochondrial ROS, and SFN-triggered cell death was ROS dependent. Comet assays revealed that SFN increased single- and double-strand DNA breaks in GBM. Compared with the vehicle control cells, a significantly higher amount of gamma-H2AX foci correlated with an increase in DNA double-strand breaks in the SFN-treated samples. Furthermore, SFN robustly inhibited the growth of GBM cell-induced cell death in established cell cultures and early-passage primary cultures and, most importantly, was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence. In vivo studies revealed that SFN administration at 100 mg/kg for 5-day cycles repeated for 3 weeks significantly decreased the growth of ectopic xenografts that were established from the early passage of primary cultures of GBM10. CONCLUSIONS These results suggest that SFN is a potent anti-GBM agent that targets several apoptosis and cell survival pathways and further preclinical and clinical studies may prove that SFN alone or in combination with other therapies may be potentially useful for GBM therapy. |
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Departments of 2 Pharmacology and Toxicology and |
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0022-3085 |
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PMID:28059653 |
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96613 |
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Navarrete-Reyes, A.P.; Medina-Rimoldi, C.T.; Avila-Funes, J.A. |
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Correlates of subjective transportation deficiency among older adults attending outpatient clinics in a tertiary care hospital in Mexico City |
Type |
Journal Article |
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Year |
2017 |
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Geriatrics & Gerontology International |
Abbreviated Journal |
Geriatr Gerontol Int |
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Keywords |
Latin America; disability; mobility; older adults; transportation |
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AIM: Older adults frequently report problems of transportation. Little is known about the correlates of transportation deficiency in Latin America. Therefore, the aim of the present study was to determine the correlates of subjective transportation deficiency (STD) among community-dwelling older adults attending a tertiary care hospital in Mexico City. METHODS: Cross-sectional study of 228 participants aged >/=70 years being followed in any of the outpatient clinics of a tertiary care hospital in Mexico City. Data were obtained through a structured questionnaire. Univariate and multivariate logistic regression analyses were carried out in order to identify the correlates of STD. RESULTS: The mean age of the participants was 79.8 years (SD 6.4) and 67.1% were women. STD was present in 46% of participants. The multivariate logistic regression model showed that female sex, illiteracy, mobility disability and the use of an assistive walking device had an independent and statistically significant association with STD. CONCLUSIONS: Female sex, illiteracy, mobility disability and the use of an assistive walking device were independent correlates of STD in the present study. Identifying the frequency and correlates of transportation deficiency in vulnerable populations will allow for the identification and implementation of useful public policies, as well as for the optimization of prevention and treatment strategies in an attempt to preserve mobility and autonomy, especially in low- and middle-income countries where previous work on transportation deficiency is lacking. Geriatr Gerontol Int 2016; : -**. |
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Research Center INSERM, Bordeaux, France |
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1447-0594 |
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PMID:28190303 |
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ref @ user @ |
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97045 |
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Navarrete-Reyes, A.P.; Medina-Rimoldi, C.T.; Avila-Funes, J.A. |
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Title |
Correlates of subjective transportation deficiency among older adults attending outpatient clinics in a tertiary care hospital in Mexico City |
Type |
Journal Article |
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Year |
2017 |
Publication |
Geriatrics & Gerontology International |
Abbreviated Journal |
Geriatr Gerontol Int |
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Keywords |
Latin America; disability; mobility; older adults; transportation |
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AIM: Older adults frequently report problems of transportation. Little is known about the correlates of transportation deficiency in Latin America. Therefore, the aim of the present study was to determine the correlates of subjective transportation deficiency (STD) among community-dwelling older adults attending a tertiary care hospital in Mexico City. METHODS: Cross-sectional study of 228 participants aged >/=70 years being followed in any of the outpatient clinics of a tertiary care hospital in Mexico City. Data were obtained through a structured questionnaire. Univariate and multivariate logistic regression analyses were carried out in order to identify the correlates of STD. RESULTS: The mean age of the participants was 79.8 years (SD 6.4) and 67.1% were women. STD was present in 46% of participants. The multivariate logistic regression model showed that female sex, illiteracy, mobility disability and the use of an assistive walking device had an independent and statistically significant association with STD. CONCLUSIONS: Female sex, illiteracy, mobility disability and the use of an assistive walking device were independent correlates of STD in the present study. Identifying the frequency and correlates of transportation deficiency in vulnerable populations will allow for the identification and implementation of useful public policies, as well as for the optimization of prevention and treatment strategies in an attempt to preserve mobility and autonomy, especially in low- and middle-income countries where previous work on transportation deficiency is lacking. Geriatr Gerontol Int 2016; : -**. |
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Research Center INSERM, Bordeaux, France |
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PMID:28190303 |
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ref @ user @ |
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97085 |
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Author |
Navarrete-Reyes, A.P.; Medina-Rimoldi, C.T.; Avila-Funes, J.A. |
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Title |
Correlates of subjective transportation deficiency among older adults attending outpatient clinics in a tertiary care hospital in Mexico City |
Type |
Journal Article |
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Year |
2017 |
Publication |
Geriatrics & Gerontology International |
Abbreviated Journal |
Geriatr Gerontol Int |
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Keywords |
Latin America; disability; mobility; older adults; transportation |
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AIM: Older adults frequently report problems of transportation. Little is known about the correlates of transportation deficiency in Latin America. Therefore, the aim of the present study was to determine the correlates of subjective transportation deficiency (STD) among community-dwelling older adults attending a tertiary care hospital in Mexico City. METHODS: Cross-sectional study of 228 participants aged >/=70 years being followed in any of the outpatient clinics of a tertiary care hospital in Mexico City. Data were obtained through a structured questionnaire. Univariate and multivariate logistic regression analyses were carried out in order to identify the correlates of STD. RESULTS: The mean age of the participants was 79.8 years (SD 6.4) and 67.1% were women. STD was present in 46% of participants. The multivariate logistic regression model showed that female sex, illiteracy, mobility disability and the use of an assistive walking device had an independent and statistically significant association with STD. CONCLUSIONS: Female sex, illiteracy, mobility disability and the use of an assistive walking device were independent correlates of STD in the present study. Identifying the frequency and correlates of transportation deficiency in vulnerable populations will allow for the identification and implementation of useful public policies, as well as for the optimization of prevention and treatment strategies in an attempt to preserve mobility and autonomy, especially in low- and middle-income countries where previous work on transportation deficiency is lacking. Geriatr Gerontol Int 2016; : -**. |
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Research Center INSERM, Bordeaux, France |
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PMID:28190303 |
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ref @ user @ |
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97125 |
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Author |
Navarrete-Reyes, A.P.; Medina-Rimoldi, C.T.; Avila-Funes, J.A. |
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Title |
Correlates of subjective transportation deficiency among older adults attending outpatient clinics in a tertiary care hospital in Mexico City |
Type |
Journal Article |
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Year |
2017 |
Publication |
Geriatrics & Gerontology International |
Abbreviated Journal |
Geriatr Gerontol Int |
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Volume |
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Pages |
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Keywords |
Latin America; disability; mobility; older adults; transportation |
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Abstract |
AIM: Older adults frequently report problems of transportation. Little is known about the correlates of transportation deficiency in Latin America. Therefore, the aim of the present study was to determine the correlates of subjective transportation deficiency (STD) among community-dwelling older adults attending a tertiary care hospital in Mexico City. METHODS: Cross-sectional study of 228 participants aged >/=70 years being followed in any of the outpatient clinics of a tertiary care hospital in Mexico City. Data were obtained through a structured questionnaire. Univariate and multivariate logistic regression analyses were carried out in order to identify the correlates of STD. RESULTS: The mean age of the participants was 79.8 years (SD 6.4) and 67.1% were women. STD was present in 46% of participants. The multivariate logistic regression model showed that female sex, illiteracy, mobility disability and the use of an assistive walking device had an independent and statistically significant association with STD. CONCLUSIONS: Female sex, illiteracy, mobility disability and the use of an assistive walking device were independent correlates of STD in the present study. Identifying the frequency and correlates of transportation deficiency in vulnerable populations will allow for the identification and implementation of useful public policies, as well as for the optimization of prevention and treatment strategies in an attempt to preserve mobility and autonomy, especially in low- and middle-income countries where previous work on transportation deficiency is lacking. Geriatr Gerontol Int 2016; : -**. |
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Research Center INSERM, Bordeaux, France |
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1447-0594 |
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PMID:28190303 |
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Call Number |
ref @ user @ |
Serial |
97146 |
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