toggle visibility Search & Display Options

Select All    Deselect All
 |   | 
Details
   print
  Records Links
Author Li, M.; Xiao, A.; Floyd, D.; Olmez, I.; Lee, J.; Godlewski, J.; Bronisz, A.; Bhat, K.P.L.; Sulman, E.P.; Nakano, I.; Purow, B. url  doi
openurl 
  Title CDK4/6 inhibition is more active against the glioblastoma proneural subtype Type Journal Article
  Year 2017 Publication Oncotarget Abbreviated Journal Oncotarget  
  Volume 8 Issue 33 Pages 55319-55331  
  Keywords Cdk4/6; glioblastoma; mesenchymal; palbociclib; proneural  
  Abstract Glioblastoma (GBM) is the most common and lethal brain tumor. Gene expression profiling has classified GBM into distinct subtypes, including proneural, mesenchymal, and classical, and identifying therapeutic vulnerabilities of these subtypes is an extremely high priority. We leveraged The Cancer Genome Atlas (TCGA) data, in particular for microRNA expression, to seek druggable core pathways in GBM. The E2F1-regulated miR-17 92 cluster and its analogs are shown to be highly expressed in proneural GBM and in GSC lines, suggesting the E2F cell cycle pathway might be a key driver in proneural GBM. Consistently, CDK4/6 inhibition with palbociclib preferentially inhibited cell proliferation in vitro in a majority of proneural GSCs versus those of other subtypes. Palbociclib treatment significantly prolonged survival of mice with established intracranial xenografts of a proneural GSC line. We show that most of these sensitive PN GSCs expressed higher levels of CDK6 and had intact Rb1, while two GSC lines with CDK4 overexpression and null Rb1 were highly resistant to palbociclib. Importantly, palbociclib treatment of proneural GSCs upregulated mesenchymal-associated markers and downregulated proneural-associated markers, suggesting that CDK4/6 inhibition induced proneural-mesenchymal transition and underscoring the enhanced role of the E2F cell cycle pathway in the proneural subtype. Lastly, the combination of palbociclib and N,N-diethylaminobenzaldehyde, an inhibitor of the mesenchymal driver ALDH1A3, showed strong synergistic inhibitory effects against proneural GSC proliferation. Taken together, our results reveal that proneural GBM has increased vulnerability to CDK4/6 inhibition, and the proneural subtype undergoes dynamic reprogramming upon palbociclib treatment-suggesting the need for a combination therapeutic strategy.  
  Address (down) Neuro-Oncology Division, Department of Neurology, University of Virginia, Charlottesville, VA, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1949-2553 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28903422 Approved no  
  Call Number ref @ user @ Serial 96569  
Permanent link to this record
 

 
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. url  doi
openurl 
  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 (down) National Institute of Neoplastic Diseases, Lima, Peru  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1470-2045 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28971826 Approved no  
  Call Number ref @ user @ Serial 97626  
Permanent link to this record
 

 
Author Herrera-Ballesteros, V.H.; Zuniga, J.; Moreno, I.; Gomez, B.; Roa-Rodriguez, R. url  doi
openurl 
  Title [Quitting smoking and willingness to pay for cessation in Panama] Type Journal Article
  Year 2017 Publication Salud Publica de Mexico Abbreviated Journal Salud Publica Mex  
  Volume 59Suppl 1 Issue Suppl 1 Pages 54-62  
  Keywords  
  Abstract Objective:: To characterize the desire for cessation and willingness to pay for abandonment therapy. Materials and methods:: The data source is the Global Adult Tobacco Survey (GATS). Cessation and willingness to pay were characterized by sociodemographic (SD) and socioeconomic (SE) variables. Logistic regressions were performed to estimate associations. Results:: A greater desire for cessation was observed in variables: women, education, non-governmental and inactive employees, rural areas, occasional smokers and middle income, and greater willingness to pay, in: education, over 60 years old, non-governmental, self-employed, urban area, occasional smokers and low median income. Conclusions:: There is a high relation between the desire for abandonment, and willingness to pay with SD and SE variables. Cessation therapies can be applied in work centers, and require a change of focus in the intervention.  
  Address (down) Ministerio de Salud. Panama  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Spanish Summary Language Original Title Quienes quieren dejar fumar y su disposicion a pagar por cesacion en Panama  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0036-3634 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28658453 Approved no  
  Call Number ref @ user @ Serial 98019  
Permanent link to this record
 

 
Author Thomas, A.A.; Abrey, L.E.; Terziev, R.; Raizer, J.; Martinez, N.L.; Forsyth, P.; Paleologos, N.; Matasar, M.; Sauter, C.S.; Moskowitz, C.; Nimer, S.D.; DeAngelis, L.M.; Kaley, T.; Grimm, S.; Louis, D.N.; Cairncross, J.G.; Panageas, K.S.; Briggs, S.; Faivre, G.; Mohile, N.A.; Mehta, J.; Jonsson, P.; Chakravarty, D.; Gao, J.; Schultz, N.; Brennan, C.W.; Huse, J.T.; Omuro, A. url  doi
openurl 
  Title Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma Type Journal Article
  Year 2017 Publication Neuro-Oncology Abbreviated Journal Neuro Oncol  
  Volume 19 Issue 10 Pages 1380-1390  
  Keywords 1p/19q codeletion; anaplastic oligodendroglioma; autologous stem cell transplant; temozolomide  
  Abstract Background: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) as a potential strategy to defer radiotherapy. Methods: Patients with AO/AOA received 6 cycles of TMZ (200 mg/m2 x 5/28 day). Responding patients were eligible for HDC (thiotepa 250 mg/m2/day x 3 days, then busulfan 3.2 mg/kg/day x 3 days), followed by ASCT. Genomic characterization was performed using next-generation sequencing. Results: Forty-one patients were enrolled; 85% had 1p/19q codeleted tumors. After induction, 26 patients were eligible for HDC-ASCT and 21 agreed to proceed. There were no unexpected adverse events or toxic deaths. After median follow-up of 66 months, 2-year progression-free survival (PFS) for transplanted patients was 86%, 5-year PFS 60%, and no patient has died. Among all 1p/19q codeleted patients (N = 33), 5-year PFS was 50% and 5-year overall survival (OS) 93%, with median time to radiotherapy not reached. Next-generation sequencing disclosed typical oligodendroglioma-related mutations, including IDH1, TERT, CIC, and FUBP1 mutations in 1p/19q codeleted patients, and glioblastoma-like signatures in 1p/19q intact patients. Aside from IDH1, potentially oncogenic/actionable mutations were variable, depicting wide molecular heterogeneity within oligodendroglial tumors. Conclusions: TMZ followed by HDC-ASCT can be safely administered to patients with newly diagnosed 1p/19q codeleted AO. This strategy was associated with promising PFS and OS, suggesting that a chemotherapy-based approach may delay the need for radiotherapy and radiation-related toxicities. Raw data for further genomic and meta-analyses are publicly available at http://cbioportal.org/study?id=odgmsk2017, accessed 6 January 2017. Clinicaltrials.gov registry: NCT00588523.  
  Address (down) Memorial Sloan Kettering Cancer Center, New York, New York,USA; Northwestern Memorial Hospital, Chicago, Illinois, USA; NorthShore University, Evanston, Illinois,USA; University of Calgary, Calgary, Alberta, Canada; Massachusetts General Hospital, Boston, Massachusetts, USA; MD Anderson Cancer Center, Houston, Texas, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1522-8517 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28472509 Approved no  
  Call Number ref @ user @ Serial 96586  
Permanent link to this record
 

 
Author Goncalves, D.P.N.; Rodriguez, R.D.; Kurth, T.; Bray, L.J.; Binner, M.; Jungnickel, C.; Gur, F.N.; Poser, S.W.; Schmidt, T.L.; Zahn, D.R.T.; Androutsellis-Theotokis, A.; Schlierf, M.; Werner, C. url  doi
openurl 
  Title Enhanced targeting of invasive glioblastoma cells by peptide-functionalized gold nanorods in hydrogel-based 3D cultures Type Journal Article
  Year 2017 Publication Acta Biomaterialia Abbreviated Journal Acta Biomater  
  Volume 58 Issue Pages 12-25  
  Keywords 3D culture; Cancer stem cells; Glioblastoma Multiforme; Gold nanorods; Photothermolysis  
  Abstract Cancer stem cells (CSCs) are responsible for drug resistance, tumor recurrence, and metastasis in several cancer types, making their eradication a primary objective in cancer therapy. Glioblastoma Multiforme (GBM) tumors are usually composed of a highly infiltrating CSC subpopulation, which has Nestin as a putative marker. Since the majority of these infiltrating cells are able to elude conventional therapies, we have developed gold nanorods (AuNRs) functionalized with an engineered peptide capable of specific recognition and selective eradication of Nestin positive infiltrating GBM-CSCs. These AuNRs generate heat when irradiated by a near-infrared laser, and cause localized cell damage. Nanoparticle internalization assays performed with GBM-CSCs or Nestin negative cells cultured as two-dimensional (2D) monolayers or embedded in three-dimensional (3D) biodegradable-hydrogels of tunable mechanical properties, revealed that the AuNRs were mainly internalized by GBM-CSCs, and not by Nestin negative cells. The AuNRs were taken up via energy-dependent and caveolae-mediated endocytic mechanisms, and were localized inside endosomes. Photothermal treatments resulted in the selective elimination of GBM-CSCs through cell apoptosis, while Nestin negative cells remained viable. Results also indicated that GBM-CSCs embedded in hydrogels were more resistant to AuNR photothermal treatments than when cultured as 2D monolayers. In summary, the combination of our engineered AuNRs with our tunable hydrogel system has shown the potential to provide an in vitro platform for the evaluation and screening of AuNR-based cancer therapeutics, leading to a substantial advancement in the application of AuNRs for targeted GBM-CSC therapy. STATEMENT OF SIGNIFICANCE: There is an urgent need for reliable and efficient therapies for the treatment of Glioblastoma Multiforme (GBM), which is currently an untreatable brain tumor form with a very poor patient survival rate. GBM tumors are mostly comprised of cancer stem cells (CSCs), which are responsible for tumor reoccurrence and therapy resistance. We have developed gold nanorods functionalized with an engineered peptide capable of selective recognition and eradication of GBM-CSCs via heat generation by nanorods upon NIR irradiation. An in vitro evaluation of nanorod therapeutic activities was performed in 3D synthetic-biodegradable hydrogel models with distinct biomechanical cues, and compared to 2D cultures. Results indicated that cells cultured in 3D were more resistant to photothermolysis than in 2D systems.  
  Address (down) Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Strasse 6, 01069 Dresden, Germany  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1742-7061 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28576716 Approved no  
  Call Number ref @ user @ Serial 96583  
Permanent link to this record
Select All    Deselect All
 |   | 
Details
   print

Save Citations:
Export Records: