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Study was administratively closed by IRB
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MicroRNAs (miRNA) are molecular biomarkers that post-transcriptionally control target genes. Deregulated miRNA expression has been observed in diverse cancers. In high grade gliomas, known as glioblastomas, the investigators have identified an oncogenic miRNA, miRNA-10b (mir-10b) that is expressed at higher levels in glioblastomas than in normal brain tissue. This study tests the hypothesis that in primary glioma samples mir-10b expression patterns will serve as a prognostic and diagnostic marker. This study will also characterize the phenotypic and genotypic diversity of glioma subclasses. Furthermore, considering the critical function of anti-mir-10b in blocking established glioblastoma growth, the investigators will test in vitro the sensitivity of individual primary tumors to anti-mir-10b treatment. Tumor, blood and cerebrospinal fluid samples will be obtained from patients diagnosed with gliomas over a period of two years. These samples will be examined for mir-10b expression levels. Patient survival, as well as tumor grade and genotypic variations will be correlated to mir-10b expression levels.
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| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Patients will be followed for survival every 12 weeks +/- 1 week. | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival | 24 Months |
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Inclusion/Exclusion Criteria:
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Patients seen in the clinic who are going to be treated with surgery, radiation and medical therapy for gliomas will be eligible for the study.
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| Name | Affiliation | Role |
|---|---|---|
| Arti B Gaur, PhD | Dartmouth-Hitchcock Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tufts Medical Center | Boston | Massachusetts | 02111 | United States | ||
| Massachusetts General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17363563 | Background | Gaur A, Jewell DA, Liang Y, Ridzon D, Moore JH, Chen C, Ambros VR, Israel MA. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007 Mar 15;67(6):2456-68. doi: 10.1158/0008-5472.CAN-06-2698. | |
| 21636706 | Background | Gaur AB, Holbeck SL, Colburn NH, Israel MA. Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo. Neuro Oncol. 2011 Jun;13(6):580-90. doi: 10.1093/neuonc/nor033. |
| Label | URL |
|---|---|
| Norris Cotton Cancer Center Clinical Trial Page | View source |
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Blood, tumor tissue, cerebrospinal fluid.
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Dartmouth-Hitchcock Medical Center | Lebanon | New Hampshire | 03756 | United States |
| University of Vermont | Burlington | Vermont | 05405 | United States |
| 18990124 | Background | Sathornsumetee S, Rich JN. Designer therapies for glioblastoma multiforme. Ann N Y Acad Sci. 2008 Oct;1142:108-32. doi: 10.1196/annals.1444.009. |
| 20030624 | Background | Lo HW. EGFR-targeted therapy in malignant glioma: novel aspects and mechanisms of drug resistance. Curr Mol Pharmacol. 2010 Jan;3(1):37-52. doi: 10.2174/1874467211003010037. |
| 19429483 | Background | Nagarajan RP, Costello JF. Epigenetic mechanisms in glioblastoma multiforme. Semin Cancer Biol. 2009 Jun;19(3):188-97. doi: 10.1016/j.semcancer.2009.02.005. Epub 2009 Feb 20. |
| 20205684 | Background | Quick A, Patel D, Hadziahmetovic M, Chakravarti A, Mehta M. Current therapeutic paradigms in glioblastoma. Rev Recent Clin Trials. 2010 Jan;5(1):14-27. doi: 10.2174/157488710790820544. |
| 15758009 | Background | Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330. |
| 6255368 | Background | Salcman M. Survival in glioblastoma: historical perspective. Neurosurgery. 1980 Nov;7(5):435-9. doi: 10.1227/00006123-198011000-00001. |
| 11937180 | Background | Stewart LA. Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet. 2002 Mar 23;359(9311):1011-8. doi: 10.1016/s0140-6736(02)08091-1. |
| 11300335 | Background | Brada M, Hoang-Xuan K, Rampling R, Dietrich PY, Dirix LY, Macdonald D, Heimans JJ, Zonnenberg BA, Bravo-Marques JM, Henriksson R, Stupp R, Yue N, Bruner J, Dugan M, Rao S, Zaknoen S. Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse. Ann Oncol. 2001 Feb;12(2):259-66. doi: 10.1023/a:1008382516636. |
| 12672279 | Background | Westphal M, Hilt DC, Bortey E, Delavault P, Olivares R, Warnke PC, Whittle IR, Jaaskelainen J, Ram Z. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol. 2003 Apr;5(2):79-88. doi: 10.1093/neuonc/5.2.79. |
| 10802656 | Background | Holland EC, Celestino J, Dai C, Schaefer L, Sawaya RE, Fuller GN. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat Genet. 2000 May;25(1):55-7. doi: 10.1038/75596. |
| 11431323 | Background | Sonoda Y, Ozawa T, Hirose Y, Aldape KD, McMahon M, Berger MS, Pieper RO. Formation of intracranial tumors by genetically modified human astrocytes defines four pathways critical in the development of human anaplastic astrocytoma. Cancer Res. 2001 Jul 1;61(13):4956-60. |
| 17974913 | Background | Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, Chin L, DePinho RA, Cavenee WK. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007 Nov 1;21(21):2683-710. doi: 10.1101/gad.1596707. |
| 18493853 | Background | Dell'Albani P. Stem cell markers in gliomas. Neurochem Res. 2008 Dec;33(12):2407-15. doi: 10.1007/s11064-008-9723-8. Epub 2008 May 21. |
| 17699746 | Background | Standart N, Jackson RJ. MicroRNAs repress translation of m7Gppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation. Genes Dev. 2007 Aug 15;21(16):1975-82. doi: 10.1101/gad.1591507. No abstract available. |
| 15659339 | Background | de Moor CH, Meijer H, Lissenden S. Mechanisms of translational control by the 3' UTR in development and differentiation. Semin Cell Dev Biol. 2005 Feb;16(1):49-58. doi: 10.1016/j.semcdb.2004.11.007. Epub 2005 Jan 12. |
| 17096367 | Background | Zhang B, Wang Q, Pan X. MicroRNAs and their regulatory roles in animals and plants. J Cell Physiol. 2007 Feb;210(2):279-89. doi: 10.1002/jcp.20869. |
| 16099643 | Background | Miska EA. How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev. 2005 Oct;15(5):563-8. doi: 10.1016/j.gde.2005.08.005. |
| 16518686 | Background | Sevignani C, Calin GA, Siracusa LD, Croce CM. Mammalian microRNAs: a small world for fine-tuning gene expression. Mamm Genome. 2006 Mar;17(3):189-202. doi: 10.1007/s00335-005-0066-3. Epub 2006 Mar 3. |
| 17618441 | Background | Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007 Aug;114(2):97-109. doi: 10.1007/s00401-007-0243-4. Epub 2007 Jul 6. |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D009837 | Oligodendroglioma |
| D005909 | Glioblastoma |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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