| Records |
| Author |
Jin, W.-L.; Mao, X.-Y.; Qiu, G.-Z. |
| Title |
Targeting Deubiquitinating Enzymes in Glioblastoma Multiforme: Expectations and Challenges |
Type |
Journal Article |
| Year |
2017 |
Publication |
Medicinal Research Reviews |
Abbreviated Journal |
Med Res Rev |
| Volume |
37 |
Issue |
3 |
Pages  |
627-661 |
| Keywords |
Animals; Carcinogenesis/pathology; Deubiquitinating Enzymes/antagonists & inhibitors/*metabolism; Enzyme Inhibitors/pharmacology; Glioblastoma/*enzymology/*therapy; Humans; *Molecular Targeted Therapy; Neoplastic Stem Cells/drug effects/pathology; DUB inhibitor; DUBs; glioblastoma; glioma stem cells; proteasome |
| Abstract |
Glioblastoma (GBM) is regarded as the most common primary intracranial neoplasm. Despite standard treatment with tumor resection and radiochemotherapy, the outcome remains gloomy. It is evident that a combination of oncogenic gain of function and tumor-suppressive loss of function has been attributed to glioma initiation and progression. The ubiquitin-proteasome system is a well-orchestrated system that controls the fate of most proteins by striking a dynamic balance between ubiquitination and deubiquitination of substrates, having a profound influence on the modulation of oncoproteins, tumor suppressors, and cellular signaling pathways. In recent years, deubiquitinating enzymes (DUBs) have emerged as potential anti-cancer targets due to their targeting several key proteins involved in the regulation of tumorigenesis, apoptosis, senescence, and autophagy. This review attempts to summarize recent studies of GBM-associated DUBs, their roles in various cellular processes, and discuss the relation between DUBs deregulation and gliomagenesis, especially how DUBs regulate glioma stem cells pluripotency, microenvironment, and resistance of radiation and chemotherapy through core stem-cell transcriptional factors. We also review recent achievements and progress in the development of potent and selective reversible inhibitors of DUBs, and attempted to find a potential GBM treatment by DUBs intervention. |
| Address |
Department of Neurosurgery, General Hospital of Jinan Military Command, Jinan, 250031, P. R. China |
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English |
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| ISSN |
0198-6325 |
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| Notes |
PMID:27775833 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96629 |
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| Author |
Behling, F.; Kaltenstadler, M.; Noell, S.; Schittenhelm, J.; Bender, B.; Eckert, F.; Tabatabai, G.; Tatagiba, M.; Skardelly, M. |
| Title |
The Prognostic Impact of Ventricular Opening in Glioblastoma Surgery: A Retrospective Single Center Analysis |
Type |
Journal Article |
| Year |
2017 |
Publication |
World Neurosurgery |
Abbreviated Journal |
World Neurosurg |
| Volume |
106 |
Issue |
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Pages |
615-624 |
| Keywords |
Extent of resection; Glioblastoma; Hydrocephalus; Overall survival; Prognosis; Tumor volume; Ventricle opening |
| Abstract |
OBJECTIVE: Ventricular opening during glioblastoma (GBM) resection is controversial. Sufficient evidence regarding its prognostic role is missing. We investigated the impact of ventricular opening on overall survival (OS), hydrocephalus development, and postoperative morbidity in patients with GBM. METHODS: Patients who underwent primary GBM resection between 2006 and 2013 were assessed retrospectively. Established predictors for overall survival (age, Karnofsky Performance Status, extent of resection, O-6-methylguanine-DNA methyltransferase promoter methylation status, isocitrate dehydrogenase mutation status) and further clinical data (postoperative status, further treatment, preoperative tumor volume, proximity to the ventricle) were included in univariate and multivariate analyses. RESULTS: Thirteen (5.7%) of 229 patients developed a hydrocephalus. Multivariate logistic regression showed that neither ventricular opening, tumor size, proximity to the ventricle, nor extent of resection were significant risk factors for hydrocephalus. Ventricular opening did not delay postoperative therapy and was not associated with neurological morbidity. Kaplan-Meier analysis demonstrated that patients who underwent ventricular opening (n = 114) exhibited a median OS of 14.3 months (12.9-16.5), whereas patients who did not undergo ventricular opening (n = 115) exhibited a median OS of 18.6 months (16.1-20.8). However, multivariate Cox regression (n = 134) did not confirm ventricular opening as an independent negative predictor of OS (risk ratio 1.09, P = 0.77). Instead, it showed that a greater preoperative tumor volume >22.8 cm3 was a negative predictor of OS (risk ratio 1.76, P = 0.02). CONCLUSIONS: Because extent of resection is a strong independent predictor of OS and ventricular opening is safe, neurosurgeons should consider ventricular opening to achieve maximal tumor resection. |
| Address |
Department of Neurosurgery, University Hospital Tuebingen, Eberhard Karls University, Tuebingen, Germany; Center for CNS Tumors, Comprehensive Cancer Center Tuebingen Stuttgart, University Hospital Tuebingen, Eberhard Karls University, Tuebingen, Germany |
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English |
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| ISSN |
1878-8750 |
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| Notes |
PMID:28729143 |
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no |
| Call Number |
ref @ user @ |
Serial |
96576 |
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| Author |
Vidaurre, T.; Santos, C.; Gomez, H.; Sarria, G.; Amorin, E.; Lopez, M.; Regalado, R.; Manrique, J.; Tarco, D.; Ayestas, C.; Calderon, M.; Mas, L.; Neciosup, S.; Salazar, M.; Chavez, J.C.; Ubillus, M.; Limache, A.; Ubillus, J.C.; Navarro, J.; Sarwal, K.; Sutcliffe, S.; Gutierrez-Aguado, A.; Silva, M.; Mena, A.; Guillen, M.E.; Castaneda, C.; Abugattas, J. |
| Title |
The implementation of the Plan Esperanza and response to the imPACT Review |
Type |
Journal Article |
| Year |
2017 |
Publication |
The Lancet. Oncology |
Abbreviated Journal |
Lancet Oncol |
| Volume |
18 |
Issue |
10 |
Pages |
e595-e606 |
| Keywords |
Delivery of Health Care/organization & administration; Developing Countries; Early Detection of Cancer/*economics; Female; Health Care Costs; *Health Expenditures; Health Planning/*organization & administration; Humans; Male; Needs Assessment; Peru; Poverty; Preventive Medicine/*organization & administration; Risk Assessment |
| Abstract |
Following the implementation of the National Cancer Prevention and Control Results-based Budget Programme (PpR Cancer-024) in 2011, the Peruvian Government approved the Plan Esperanza-a population-based national cancer control plan-in 2012. Legislation that ensured full government-supported funding for people who were otherwise unable to access or afford care and treatment accompanied the Plan. In 2013, the Ministry of Health requested an integrated mission of the Programme of Action for Cancer Therapy (imPACT) report to strengthen cancer control in Peru. The imPACT Review, which was executed in 2014, assessed Peru's achievements in cancer control, and areas for improvement, including cancer control planning, further development of population-based cancer registration, increased prevention, early diagnosis, treatment and palliative care, and the engagement and participation of civil society in the health-care system. This Series paper gives a brief history of the development of the Plan Esperanza, describes the innovative funding model that supports it, and summarises how funds are disseminated on the basis of disease, geography, and demographics. An overview of the imPACT Review, and the government's response in the context of the Plan Esperanza, is provided. The development and execution of the Plan Esperanza and the execution of and response to the imPACT Review demonstrates the Peruvian Government's commitment to fighting cancer across the country, including in remote and urban areas. |
| Address |
National Institute of Neoplastic Diseases, Lima, Peru |
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English |
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1470-2045 |
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| Notes |
PMID:28971826 |
Approved |
no |
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ref @ user @ |
Serial |
97626 |
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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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0006-3002 |
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| Notes |
PMID:28040478 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96615 |
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| Author |
Sousa, K. de M.; Oliveira, W.I.F. de; Melo, L.O.M. de; Alves, E.A.; Piuvezam, G.; Gama, Z.A. da S. |
| Title |
A qualitative study analyzing access to physical rehabilitation for traffic accident victims with severe disability in Brazil |
Type |
Journal Article |
| Year |
2017 |
Publication |
Disability and Rehabilitation |
Abbreviated Journal |
Disabil Rehabil |
| Volume |
39 |
Issue |
6 |
Pages |
568-577 |
| Keywords |
Brazil; health services accessibility; quality of health care; rehabilitation; traffic accidents |
| Abstract |
Purpose To identify access barriers to physical rehabilitation for traffic accident (TA) victims with severe disability and build a theoretical model to provide guidance towards the improvement of these services. Methods Qualitative research carried out in the city of Natal (Northeast Brazil), with semi-structured interviews with 120 subjects (19 key informer health professionals and 101 TA victims) identified in a database made available by the emergency hospital. The interviews were analyzed using Alceste software, version 4.9. Results The main barriers present in the interviews were: (1) related to services: bureaucratic administrative practises, low offer of rehabilitation services, insufficient information on rehabilitation, lack of guidelines that integrate hospital and ambulatory care and (2) related to patients: financial difficulties, functional limitations, geographic distance, little information on health, association with low education levels and disbelief in the system and in rehabilitation. Conclusion The numerous access barriers were presented in a theoretical model with causes related to organizational structure, processes of care, professionals and patients. This model must be tested by health policy-makers and managers to improve the quality of physical rehabilitation and avoid unnecessary prolongation of the suffering and disability experienced by TA survivors. Implications for rehabilitation Traffic accidents (TAs) are a global health dilemma that demands integrality of preventive actions, pre-hospital and hospital care and physical rehabilitation (PR). This study lays the foundation for improving access to PR for TA survivors, an issue of quality of care that results in preventable disabilities. The words of the patients interviewed reveal the suffering of victims, which is often invisible to society and given low priority by health policies that relegate PR to a second plan ahead of prevention and urgent care. A theoretical model of the causes of the problem of access to PR was built. The identified barriers are potentially preventable through the intervention of health policy-makers, managers, regulators and rehabilitation professionals, and by encouraging the participation of patients. Addressing timely access barriers involves the expansion of the supply of services and rehabilitation professionals, regulation and standardization of referencing practises and encouraging the provision of information to patients about continuity of care and their health needs. |
| Address |
d Department of Collective Health, Federal University of Rio Grande Do Norte , Natal , Brazil |
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English |
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0963-8288 |
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| Notes |
PMID:26987029 |
Approved |
no |
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ref @ user @ |
Serial |
97458 |
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