| Records |
| 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. |
| Title |
Cathepsin K cleavage of SDF-1alpha inhibits its chemotactic activity towards glioblastoma stem-like cells |
Type |
Journal Article |
| Year |
2017 |
Publication |
Biochimica et Biophysica Acta |
Abbreviated Journal |
Biochim Biophys Acta |
Volume  |
1864 |
Issue |
3 |
Pages |
594-603 |
| 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 |
| 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. |
| Address |
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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English |
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| ISSN |
0006-3002 |
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| Notes |
PMID:28040478 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96615 |
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| Author |
Castillo, M.E.; Molina, J.R.; Rodriguez Y Silva, F.; Garcia-Chevesich, P.; Garfias, R. |
| Title |
A system to evaluate fire impacts from simulated fire behavior in Mediterranean areas of Central Chile |
Type |
Journal Article |
| Year |
2017 |
Publication |
The Science of the Total Environment |
Abbreviated Journal |
Sci Total Environ |
| Volume |
579 |
Issue |
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Pages |
1410-1418 |
| Keywords |
Wildfire behavior; Wildfire intensity; Wildfire simulation |
| Abstract |
Wildfires constitute the greatest economic disruption to Mediterranean ecosystems, from a socio-economic and ecological perspective (Molina et al., 2014). This study proposes to classify fire intensity levels based on potential fire behavior in different types of Mediterranean vegetation types, using two geographical scales. The study considered >4 thousand wildfires over a period of 25years, identifying fire behavior on each event, based on simulations using “KITRAL”, a model developed in Chile in 1993 and currently used in the entire country. Fire intensity values allowed results to be classified into six fire effects categories (levels), each of them with field indicators linking energy values with damage related to burned vegetation and wildland urban interface zone. These indicators also facilitated a preliminary assessment of wildfire impact on different Mediterranean land uses and, are therefore, a useful tool to prioritize future interventions. |
| Address |
International Hydrology Research Group, Faculty of Forest Sciences and Nature Conservancy, University of Chile |
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English |
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0048-9697 |
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| Notes |
PMID:27923572 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
97511 |
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| Author |
Firmansyah, I.; Spiller, M.; de Ruijter, F.J.; Carsjens, G.J.; Zeeman, G. |
| Title |
Assessment of nitrogen and phosphorus flows in agricultural and urban systems in a small island under limited data availability |
Type |
Journal Article |
| Year |
2017 |
Publication |
The Science of the Total Environment |
Abbreviated Journal |
Sci Total Environ |
| Volume |
574 |
Issue |
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Pages |
1521-1532 |
| Keywords |
Nitrogen; Phosphorus; Small island system; Substance Flow Analysis (SFA); Urban metabolism; Urban-agriculture |
| Abstract |
Nitrogen (N) and phosphorus (P) are two essential macronutrients required in agricultural production. The major share of this production relies on chemical fertilizer that requires energy and relies on limited resources (P). Since these nutrients are lost to the environment, there is a need to shift from this linear urban metabolism to a circular metabolism in which N and P from domestic waste and wastewater are reused in agriculture. A first step to facilitate a transition to more circular urban N and P management is to understand the flows of these resources in a coupled urban-agricultural system. For the first time this paper presents a Substance Flow Analysis (SFA) approach for the assessment of the coupled agricultural and urban systems under limited data availability in a small island. The developed SFA approach is used to identify intervention points that can provide N and P stocks for agricultural production. The island of St. Eustatius, a small island in the Caribbean, was used as a case study. The model developed in this study consists of eight sub-systems: agricultural and natural lands, urban lands, crop production, animal production, market, household consumption, soakage pit and open-dump landfill. A total of 26 flows were identified and quantified for a period of one year (2013). The results showed that the agricultural system is a significant source for N and P loss because of erosion/run-off and leaching. Moreover, urban sanitation systems contribute to deterioration of the island's ecosystem through N and P losses from domestic waste and wastewater by leaching and atmospheric emission. Proposed interventions are the treatment of blackwater and greywater for the recovery of N and P. In conclusion, this study allows for identification of potential N and P losses and proposes mitigation measures to improve nutrient management in a small island context. |
| Address |
Sub-department of Environmental Technology, Wageningen UR, Bornse Weilanden 9, 6708 WG Wageningen, The Netherlands |
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English |
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0048-9697 |
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| Notes |
PMID:27613673 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
97161 |
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| Author |
Firmansyah, I.; Spiller, M.; de Ruijter, F.J.; Carsjens, G.J.; Zeeman, G. |
| Title |
Assessment of nitrogen and phosphorus flows in agricultural and urban systems in a small island under limited data availability |
Type |
Journal Article |
| Year |
2017 |
Publication |
The Science of the Total Environment |
Abbreviated Journal |
Sci Total Environ |
| Volume |
574 |
Issue |
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Pages |
1521-1532 |
| Keywords |
Nitrogen; Phosphorus; Small island system; Substance Flow Analysis (SFA); Urban metabolism; Urban-agriculture |
| Abstract |
Nitrogen (N) and phosphorus (P) are two essential macronutrients required in agricultural production. The major share of this production relies on chemical fertilizer that requires energy and relies on limited resources (P). Since these nutrients are lost to the environment, there is a need to shift from this linear urban metabolism to a circular metabolism in which N and P from domestic waste and wastewater are reused in agriculture. A first step to facilitate a transition to more circular urban N and P management is to understand the flows of these resources in a coupled urban-agricultural system. For the first time this paper presents a Substance Flow Analysis (SFA) approach for the assessment of the coupled agricultural and urban systems under limited data availability in a small island. The developed SFA approach is used to identify intervention points that can provide N and P stocks for agricultural production. The island of St. Eustatius, a small island in the Caribbean, was used as a case study. The model developed in this study consists of eight sub-systems: agricultural and natural lands, urban lands, crop production, animal production, market, household consumption, soakage pit and open-dump landfill. A total of 26 flows were identified and quantified for a period of one year (2013). The results showed that the agricultural system is a significant source for N and P loss because of erosion/run-off and leaching. Moreover, urban sanitation systems contribute to deterioration of the island's ecosystem through N and P losses from domestic waste and wastewater by leaching and atmospheric emission. Proposed interventions are the treatment of blackwater and greywater for the recovery of N and P. In conclusion, this study allows for identification of potential N and P losses and proposes mitigation measures to improve nutrient management in a small island context. |
| Address |
Sub-department of Environmental Technology, Wageningen UR, Bornse Weilanden 9, 6708 WG Wageningen, The Netherlands |
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English |
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0048-9697 |
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| Notes |
PMID:27613673 |
Approved |
no |
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ref @ user @ |
Serial |
97517 |
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| Author |
Miranda, A.; Blanco-Prieto, M.; Sousa, J.; Pais, A.; Vitorino, C. |
| Title |
Breaching barriers in glioblastoma. Part I: Molecular pathways and novel treatment approaches |
Type |
Journal Article |
| Year |
2017 |
Publication |
International Journal of Pharmaceutics |
Abbreviated Journal |
Int J Pharm |
| Volume |
531 |
Issue |
1 |
Pages |
372-388 |
| Keywords |
Glioblastoma; Molecular mechanisms; Temozolomide; Therapeutic advances; Therapeutic resistance |
| Abstract |
Glioblastoma multiforme (GBM) is the most common primary brain tumour, and the most aggressive in nature. The prognosis for patients with GBM remains poor, with a median survival time of only 1-2 years. The treatment failure relies on the development of resistance by tumour cells and the difficulty of ensuring that drugs effectively cross the dual blood brain barrier/blood brain tumour barrier. The advanced molecular and genetic knowledge has allowed to identify the mechanisms responsible for temozolomide resistance, which represents the standard of care in GBM, along with surgical resection and radiotherapy. Such resistance has motivated the researchers to investigate new avenues for GBM treatment intended to improve patient survival. In this review, we provide an overview of major obstacles to effective treatment of GBM, encompassing biological barriers, cancer stem cells, DNA repair mechanisms, deregulated signalling pathways and autophagy. New insights and potential therapy approaches for GBM are also discussed, emphasizing localized chemotherapy delivered directly to the brain, immunotherapy, gene therapy and nanoparticle-mediated brain drug delivery. |
| Address |
Faculty of Pharmacy, University of Coimbra, Portugal; Pharmacometrics Group of the Centre for Neurosciences and Cell Biology (CNC), University of Coimbra, Portugal. Electronic address: csvitorino@ff.uc.pt |
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English |
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0378-5173 |
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| Notes |
PMID:28755993 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96574 |
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