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Bioluminescent In Vivo Imaging of Orthotopic Glioblastoma Xenografts in Mice
Frenster, Joshua D; Placantonakis, Dimitris G
Orthotopic rodent xenografts are an essential tool for studying glioblastoma in vivo. Xenograft growth as a function of time can only be monitored by noninvasive imaging. This chapter describes in detail how to assess xenograft size and growth using bioluminescent imaging with IVIS (in vivo imaging system). This form of imaging (a) can be performed without the help of a trained technician, (b) is a very quick procedure, allowing simultaneous imaging of up to five animals at a total experimental duration of 15 min, and (c) is cheaper than the alternatives (small animal MRI or CT). This technique relies on the stable expression of luciferase by the xenografted GBM cells. Luciferin, the substrate of luciferase, which is injected into host mice intraperitoneally, distributes throughout the mouse body and crosses the blood brain barrier. Luciferase expressed by the xenografted cells uses this substrate in a catalytic reaction, leading to the emission of visible light, which is detected by the CCD camera of the IVIS imaging system. The intensity of this emitted light correlates to the size of a given xenograft and allows comparisons of xenograft size across different animals, as well as within the same animal across different time points.
PMID: 29392701
ISSN: 1940-6029
CID: 2933612
Orthotopic Patient-Derived Glioblastoma Xenografts in Mice
Xu, Zhongye; Kader, Michael; Sen, Rajeev; Placantonakis, Dimitris G
Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.
PMID: 29392700
ISSN: 1940-6029
CID: 2933602
Correlation between IDH mutation status, genome-wide copy number abundance and tumor blood volume in diffuse gliomas: a TCGA/TCIA project and multi-institute study [Meeting Abstract]
Wu, C -C; Poisson, L M; Neto, L; Ng, V; Patel, S; Snuderl, M; Zagzag, D; Placantonakis, D; Golfinos, J; Chi, A S; Jain, R
Purpose: Prior studies have shown correlation between relative cerebral blood volume (rCBV) and patient survival and tumor genomics. The purpose of this study was to determine whether rCBV values correlate with isocitrate dehydrogenase (IDH) mutation status, genome-wide CNV (copy number variation) and patient overall survival in diffuse gliomas. Materials & Methods: 107 treatment naive gliomas (62 patients from TCGA/TCIA dataset and 45 patients from our institute) (44 glioblastoma and 63 lower grade gliomas) with DSC T2* perfusion data were included. IDH mutation and survival data were assayed by the TCGA, and pre-surgical imaging collected by The Cancer Imaging Archive. CNVabundance plots obtained with Illumina 850k EPIC DNA methylation arrays were reviewed in 19 patients. The association of rCBV with tumor genomics, CNV and overall survival were analyzed. Results: IDH-wildtype gliomas (44.8%) demonstrated higher rCBV values (rCBV = 6.87 +/- 3.09) than IDH-mutated gliomas (55.2%, rCBV =2.21 +/- 1.71 for 1p/19q codeleted gliomas and 2.09 +/- 2.00 for non-codeleted gliomas, ANOVA, p<0.0001). rCBV is a significant predictor of overall survival (HR 1.23, p<0.0001). Gliomas with rCBV < 3.80 showed better survival (n = 54, median survival time unobserved) than gliomas with rCBV > 3.8 (n = 53, median 18 months; log-rank p<0.0001). IDHwt gliomas with high rCBV had the worst survival (10.6% surviving at 3 years, 95% CI (4%, 30%)). CNV-S IDHmut 1p19q noncodeleted gliomas demonstrated significantly lower mean rCBV (1.4 +/- 0.4) than CNV-U gliomas (4.0 +/- 1.1, p = 0.009). Conclusion: IDHwt gliomas show higher rCBV than IDHmut gliomas irrespective of the glioma grade. Higher rCBV measurements are associated with poorer survival in the entire cohort and also within IDHmut and IDHwt gliomas. IDHmut 1p19q noncodeleted gliomas with higher CNV abundance (CNV-U) also show higher CBV when compared with those with lesser degree of CNVabundance (CNV-S)
EMBASE:621458704
ISSN: 1432-1920
CID: 3028112
A Rare Case of Composite Dural Extranodal Marginal Zone Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Bustoros, Mark; Liechty, Benjamin; Zagzag, David; Liu, Cynthia; Shepherd, Timothy; Gruber, Deborah; Raphael, Bruce; Placantonakis, Dimitris G
Background/UNASSIGNED:Primary extranodal marginal zone lymphoma (MZL) of the dura is a rare neoplastic entity in the central nervous system (CNS). Methods/UNASSIGNED:We used literature searches to identify previously reported cases of primary dural MZL. We also reviewed clinical, pathologic, and radiographic data of an adult patient with concurrent dural MZL and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Results/UNASSIGNED:We identified 104 cases of dural MZL in the literature. None of them presented concurrently with another type of non-Hodgkin lymphoma. This is the first report of composite lymphoma consisting of dural MZL and CLL/SLL in the bone marrow and lymph nodes. Conclusion/UNASSIGNED:Primary dural MZL is a rare, indolent low-grade CNS lymphoma, with a relatively good prognosis. Its treatment is multidisciplinary and often requires surgical intervention due to brain compression, along with low to moderate doses of radiotherapy and/or systemic chemotherapy.
PMCID:5928293
PMID: 29740389
ISSN: 1664-2295
CID: 3085002
The posterior nasoseptal flap: A novel technique for closure after endoscopic transsphenoidal resection of pituitary adenomas
Barger, James; Siow, Matthew; Kader, Michael; Phillips, Katherine; Fatterpekar, Girish; Kleinberg, David; Zagzag, David; Sen, Chandranath; Golfinos, John G; Lebowitz, Richard; Placantonakis, Dimitris G
Background/UNASSIGNED:While effective for the repair of large skull base defects, the Hadad-Bassagasteguy nasoseptal flap increases operative time and can result in a several-week period of postoperative crusting during re-mucosalization of the denuded nasal septum. Endoscopic transsphenoidal surgery for pituitary adenoma resection is generally not associated with large dural defects and high-flow cerebrospinal fluid (CSF) leaks requiring extensive reconstruction. Here, we present the posterior nasoseptal flap as a novel technique for closure of skull defects following endoscopic resection of pituitary adenomas. This flap is raised in all surgeries during the transnasal exposure using septal mucoperiosteum that would otherwise be discarded during the posterior septectomy performed in binostril approaches. Methods/UNASSIGNED:We present a retrospective, consecutive case series of 43 patients undergoing endoscopic transsphenoidal resection of a pituitary adenoma followed by posterior nasoseptal flap placement and closure. Main outcome measures were extent of resection and postoperative CSF leak. Results/UNASSIGNED:The mean extent of resection was 97.16 ± 1.03%. Radiographic measurement showed flap length to be adequate. While a defect in the diaphragma sellae and CSF leak were identified in 21 patients during surgery, postoperative CSF leak occurred in only one patient. Conclusions/UNASSIGNED:The posterior nasoseptal flap provides adequate coverage of the surgical defect and is nearly always successful in preventing postoperative CSF leak following endoscopic transsphenoidal resection of pituitary adenomas. The flap is raised from mucoperiosteum lining the posterior nasal septum, which is otherwise resected during posterior septectomy. Because the anterior septal cartilage is not denuded, raising such flaps avoids the postoperative morbidity associated with the larger Hadad-Bassagasteguy nasoseptal flap.
PMCID:5838838
PMID: 29527390
ISSN: 2229-5097
CID: 3567912
RECURRENT HOMOZYGOUS DELETION OF DROSHA AND MICRODUPLICATION OF PDE4DIP CONTAINING THE ANCESTRAL DUF1220 DOMAIN IN PINEOBLASTOMA [Meeting Abstract]
Snuderl, Matija; Kannan, Kasthuri; Pfaff, Elke; Wang, Shiyang; Stafford, James; Serrano, Jonathan; Heguy, Adriana; Ray, Karina; Faustin, Arline; Aminova, Olga; Dolgalev, Igor; Stapleton, Stacie; Zagzag, David; Chiriboga, Luis; Gardner, Sharon; Wisoff, Jeffrey; Golfinos, John; Capper, David; Hovestadt, Volker; Rosenblum, Marc; Placantonakis, Dimitris; LeBoeuf, Sarah; Papagiannakopoulos, Thales; Chavez, Lukas; Ahsan, Sama; Eberhart, Charles; Pfister, Stefan; Jones, David; Karajannis, Matthias
ISI:000438339000189
ISSN: 1522-8517
CID: 5525552
DETECTION OF TERT MUTATIONS IN CELL-FREE CIRCULATING TUMOR DNA (cTDNA) OF GLIOBLASTOMA PATIENTS USING DROPLET DIGITAL PCR [Meeting Abstract]
Cordova, Christine; Corless, Broderick; Syeda, Mahrukh; Patel, Amie; Delara, Malcolm; Eisele, Sylvia; Schafrick, Jessica; Placantonakis, Dimitris; Pacione, Donato; Silverman, Joshua; Fatterpekar, Girish; Shepherd, Timothy; Jain, Rajan; Snuderl, Matija; Zagzag, David; Golfinos, John; Jafar, Jafar J; Shao, Yongzhao; Karlin-Neumann, George; Polsky, David; Chi, Andrew S
ISI:000415152503095
ISSN: 1523-5866
CID: 2802392
MR IMAGING PHENOTYPE CORRELATES WITH EXTENT OF GENOME-WIDE COPY NUMBER ABUNDANCE IN IDH MUTATED GLIOMAS [Meeting Abstract]
Wu, Chih-Chun; Jain, Rajan; Patel, Seema; Neto, Lucidio; Zagzag, David; Placantonakis, Dimitris; Golfinos, John; Chi, Andrew S; Snuderl, Matija
ISI:000415152502232
ISSN: 1523-5866
CID: 2802402
PERIPHERAL BLOOD DNA METHYLATION PROFILES IDENTIFY IDH1/2 MUTATION STATUS IN ADULTS WITH DIFFUSE GLIOMA [Meeting Abstract]
Kloetgen, Andreas; Serrano, Jonathan; Patel, Seema; Bowman, Christopher; Shen, Guomiao; Zagzag, David; Karajannis, Matthias; Golfinos, John; Placantonakis, Dimitris; Tsirigos, Aristotelis; Chi, Andrew S; Snuderl, Matija
ISI:000415152501194
ISSN: 1523-5866
CID: 2802432
H3 K27M MUTANT GLIOMAS ARE SELECTIVELY KILLED BY ONC201, A SMALL MOLECULE INHIBITOR OF DOPAMINE RECEPTOR D2 [Meeting Abstract]
Chi, Andrew S; Stafford, James M; Sen, Namita; Possemato, Richard; Placantonakis, Dimitris; Hidalgo, Eveline Teresa; Harter, David; Wisoff, Jeffrey; Golfinos, John; Arrillaga-Romany, Isabel; Batchelor, Tracy; Wen, Patrick; Wakimoto, Hiroaki; Cahill, Daniel; Allen, Joshua E; Oster, Wolfgang; Snuderl, Matija
ISI:000415152501151
ISSN: 1523-5866
CID: 2802442