Gerald A Grant

Stanford University, Palo Alto, California, United States

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Publications (90)392.99 Total impact

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    ABSTRACT: We present three cases of genetically confirmed Gorlin syndrome with desmoplastic medulloblastoma (DMB) in whom tumor recurred despite standard therapy. One patient was found to have a novel germline missense PTCH1 mutation. Molecular analysis of recurrent tumor using fluorescent in situ hybridization (FISH) revealed PTEN and/ or PTCH1 loss in 2 patients. Whole exome sequencing (WES) of tumor in one patient revealed loss of heterozygosity of PTCH1 and a mutation of GNAS gene in its non-coding 3' -untranslated region (UTR) with corresponding decreased protein expression. While one patient died despite high-dose chemotherapy (HDC) plus stem cell rescue (ASCR) and palliative radiotherapy, two patients are currently alive for 18+ and 120+ months respectively following retrieval therapy that did not include irradiation. Infants with DMB and GS should be treated aggressively with chemotherapy at diagnosis to prevent relapse but radiotherapy should be avoided. The use of molecular prognostic markers for DMB should be routinely used to identify the subset of tumors that might have an aggressive course. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 05/2015; DOI:10.1002/pbc.25560 · 2.56 Impact Factor
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    ABSTRACT: Large cerebral aneurysms of the basilar apex are difficult to treat. Recently, endovascular treatment has mitigated much of the morbidity associated with treating these lesions. However, the morphology of aneurysms of the vertebrobasilar system can preclude endovascular treatment. Rapid ventricular pacing (RVP) facilitates open surgical treatment of cerebral aneurysms. It can assist in reducing the pressure of the neck of the aneurysm, allowing safe application of a clip. The authors present a case of a pediatric patient who developed a basilar artery pseudoaneurysm that required surgery. Given the large size of the aneurysm, RVP was performed, allowing the surgeons to dissect the dome of the aneurysm from the surrounding tissue and pontine perforating branches away from the lesion to safely clip the lesion. The patient had an uneventful recovery. To the authors' knowledge, this represents the first known case of RVP to aid in basilar artery clip occlusion in a pediatric patient.
    Journal of Neurosurgery Pediatrics 03/2015; 15(6):1-5. DOI:10.3171/2014.11.PEDS14290 · 1.37 Impact Factor
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    ABSTRACT: Resection of brain tumors is followed by chemotherapy and radiation to ablate remaining malignant cell populations. Targeting these populations stands to reduce tumor recurrence and offer the promise of more complete therapy. Thus, improving access to the tumor, while leaving normal brain tissue unscathed, is a critical pursuit. A central challenge in this endeavor lies in the limited delivery of therapeutics to the tumor itself. The blood-brain barrier (BBB) is responsible for much of this difficulty but also provides an essential separation from systemic circulation. Due to the BBB's physical and chemical constraints, many current therapies, from cytotoxic drugs to antibody-based proteins, cannot gain access to the tumor. This review describes the characteristics of the BBB and associated changes wrought by the presence of a tumor. Current strategies for enhancing the delivery of therapies across the BBB to the tumor will be discussed, with a distinction made between strategies that seek to disrupt the BBB and those that aim to circumvent it.
    Neurosurgical FOCUS 03/2015; 38(3):E9. DOI:10.3171/2014.12.FOCUS14758 · 2.14 Impact Factor
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    ABSTRACT: Background Expression quantitative trait loci (eQTL) play an important role in the regulation of gene expression. Gene expression levels and eQTLs are expected to vary from tissue to tissue, and therefore multi-tissue analyses are necessary to fully understand complex genetic conditions in humans. Dura mater tissue likely interacts with cranial bone growth and thus may play a role in the etiology of Chiari Type I Malformation (CMI) and related conditions, but it is often inaccessible and its gene expression has not been well studied. A genetic basis to CMI has been established; however, the specific genetic risk factors are not well characterized.ResultsWe present an assessmet of eQTLs for whole blood and dura mater tissue from individuals with CMI. A joint-tissue analysis identified 239 eQTLs in either dura or blood, with 79% of these eQTLs shared by both tissues. Several identified eQTLs were novel and these implicate genes involved in bone development (IPO8, XYLT1, and PRKAR1A), and ribosomal pathways related to marrow and bone dysfunction, as potential candidates in the development of CMI.Conclusions Despite strong overall heterogeneity in expression levels between blood and dura, the majority of cis-eQTLs are shared by both tissues. The power to detect shared eQTLs was improved by using an integrative statistical approach. The identified tissue-specific and shared eQTLs provide new insight into the genetic basis for CMI and related conditions.
    BMC Genomics 01/2015; 16(1):11. DOI:10.1186/s12864-014-1211-8 · 4.04 Impact Factor
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    ABSTRACT: This preliminary study investigated whether direct measurement of head rotation improves prediction of mild traumatic brain injury (mTBI). Although many studies have implicated rotation as a primary cause of mTBI, regulatory safety standards use 3 degree-of-freedom (3DOF) translation-only kinematic criteria to predict injury. Direct 6DOF measurements of human head rotation (3DOF) and translation (3DOF) have not been previously available to examine whether additional DOFs improve injury prediction. We measured head impacts in American football, boxing, and mixed martial arts using 6DOF instrumented mouthguards, and predicted clinician-diagnosed injury using 12 existing kinematic criteria and 6 existing brain finite element (FE) criteria. Among 513 measured impacts were the first two 6DOF measurements of clinically diagnosed mTBI. For this dataset, 6DOF criteria were the most predictive of injury, more than 3DOF translation-only and 3DOF rotation-only criteria. Peak principal strain in the corpus callosum, a 6DOF FE criteria, was the strongest predictor, followed by two criteria that included rotation measurements, peak rotational acceleration magnitude and Head Impact Power (HIP). These results suggest head rotation measurements may improve injury prediction. However, more 6DOF data is needed to confirm this evaluation of existing injury criteria, and to develop new criteria that considers directional sensitivity to injury.
    Annals of Biomedical Engineering 12/2014; DOI:10.1007/s10439-014-1212-4 · 3.23 Impact Factor
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    ABSTRACT: Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease.Oncogene advance online publication, 22 September 2014; doi:10.1038/onc.2014.304.
    Oncogene 09/2014; DOI:10.1038/onc.2014.304 · 8.56 Impact Factor
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    ABSTRACT: Tumors of the central nervous system are challenging to treat due to the limited effectiveness and associated toxicities of chemotherapy and radiation therapy. For tumors that can be removed surgically, extent of malignant tissue resection has been shown to correlate with disease progression, recurrence, and survival. Thus, improved technologies for real-time brain tumor imaging are critically needed as tools for guided surgical resection. We previously engineered a novel peptide that binds with high affinity and unique specificity to αVβ3, αVβ5, and α5β1 integrins, which are present on tumor cells, and the vasculature of many cancers, including brain tumors. In the current study, we conjugated this engineered peptide to a near infrared fluorescent dye (Alexa Fluor 680), and used the resulting molecular probe for non-invasive whole body imaging of patient-derived medulloblastoma xenograft tumors implanted in the cerebellum of mice. The engineered peptide exhibited robust targeting and illumination of intracranial medulloblastoma following both intravenous and intraperitoneal injection routes. In contrast, a variant of the engineered peptide containing a scrambled integrin-binding sequence did not localize to brain tumors, demonstrating that tumor-targeting is driven by specific integrin interactions. Ex vivo imaging was used to confirm the presence of tumor and molecular probe localization to the cerebellar region. These results warrant further clinical development of the engineered peptide as a tool for image-guided resection of central nervous system tumors.
    09/2014; 6(9). DOI:10.7759/cureus.207
  • Neurosurgery 08/2014; 61 Suppl 1:N1. DOI:10.1227/NEU.0000000000000442 · 3.03 Impact Factor
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    ABSTRACT: Mild traumatic brain injury (mTBI) is a global health crisis affecting 6 in 1000 people annually. mTBI causes acute neurocognitive deficits and repeated trauma may lead to chronic neurodegeneration. Current industry safety standards use head acceleration magnitude as an indicator of mTBI. However, injury tolerance has been shown to vary substantially by direction in animal and computational studies, with both the amplitude and duration of head acceleration impulses being important factors. Injury may thus be a multi-dimensional phenomenon that spans multiple spatial and temporal dimensions. Still, this has not yet been shown in humans due to the lack of human injury measurements in all three translational and three rotational directions (six degrees of freedom or 6-DOF). We developed a novel instrumented mouthguard to measure full 6-DOF head motion in American football, boxing, and mixed martial arts. 537 head collisions from 31 subjects were collected, including two cases of mTBI: one subject lost consciousness, while the other experienced less-pronounced symptoms and self-reported the injury. We found that no single measure or pair of measures were sufficient to separate injury from non-injury. However, in three dimensions, a plane defined by two translational and one rotational measure unambiguously distinguished both injury cases from non-injury (Figure, A). This indicates the potential necessity of higher-dimensional tolerance measures to predicting mTBI. Furthermore, when plotted against an injury tolerance curve derived from prior animal and analytical models (Figure, B), the data lay near the region sensitive to both peak rotational acceleration and change in velocity over time, suggesting injury tolerance may be defined in both spatial and temporal dimensions. The benefit of a multi-dimensional injury classifier is highlighted by its ability to identify both the subtle, self-reported injury and loss of consciousness. It allows automatic and timely prediction of injury without relying on patient self-reporting, which can be delayed, subjective and potentially unreported. 6-DOF instruments such as the instrumented mouthguard may thus be developed into real-time trauma screening tools for high risk populations including athletes and soldiers. Furthermore, multi-dimensional tolerances can inform changes in industry safety standards and inspire new protective equipment design. histopathological responses following closed rotational head injury depend on direction of head motion. Experimental neurology, 227(1), 79-88.
    7th World Congress of Biomechanics, Boston, Massachusetts, USA; 07/2014
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    ABSTRACT: Human mTBI biomechanics are complex and poorly understood, rendering screening efforts ineffective. Inertial rotation and translation are thought to cause diffuse brain trauma, but human tolerance to acceleration in all rotational and translational directions (six degrees of freedom, 6DOF) has not been measured for a human injury. Using novel instrumented mouthguards that rigidly couple to the upper dentition, we measured head collision biomechanics in full 6DOF, including the first complete measurements of human mTBI. Over 500 collisions among 31 subjects were measured at American football, boxing, and mixed martial arts events. Two subjects sustained a concussion during competitive play: one suffered loss of consciousness (LOC) while the other self-reported more subtle post-concussive symptoms, including headache, impaired concentration, and slowed reaction. Using the KTH finite element (FE) model, we mapped complex spatiotemporal kinematics measured in vivo onto the brain's anatomy. The LOC injury reported the highest principal strain (50%) among 50 randomly-selected non-injury collisions and the self-reported injury. Six non-injury collisions produced higher strains than the self-reported injury (18%), but in different anatomical regions. Maximum strain in both injuries occurred in the corpus callosum, and no non-injuries reached injury strain levels in this region. The LOC injury also predicted large strains in the brainstem. Our 6DOF measurement system predicted deformation in brain structures consistent with observed neurological deficits. Injury and non-injury collisions were distinguished by the severity and location of maximum tissue strain. Damage to the corpus callosum has been shown to disrupt interhemispheric communication and affect perception, while damage to the brainstem has been shown to induce LOC. While more data is required to characterize brain tissue mechanics across a wider spectrum of injuries, congruity between our measured kinematics, predicted tissue deformations, and observed symptoms indicates the promise of this system as a clinical tool.
    2014 Symposium of the National Neurotrauma Society, San Francisco, California, USA; 06/2014
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    ABSTRACT: Background Chiari Type I Malformation (CMI) is characterized by herniation of the cerebellar tonsils through the foramen magnum at the base of the skull, resulting in significant neurologic morbidity. As CMI patients display a high degree of clinical variability and multiple mechanisms have been proposed for tonsillar herniation, it is hypothesized that this heterogeneous disorder is due to multiple genetic and environmental factors. The purpose of the present study was to gain a better understanding of what factors contribute to this heterogeneity by using an unsupervised statistical approach to define disease subtypes within a case-only pediatric population. Methods A collection of forty-four pediatric CMI patients were ascertained to identify disease subtypes using whole genome expression profiles generated from patient blood and dura mater tissue samples, and radiological data consisting of posterior fossa (PF) morphometrics. Sparse k-means clustering and an extension to accommodate multiple data sources were used to cluster patients into more homogeneous groups using biological and radiological data both individually and collectively. Results All clustering analyses resulted in the significant identification of patient classes, with the pure biological classes derived from patient blood and dura mater samples demonstrating the strongest evidence. Those patient classes were further characterized by identifying enriched biological pathways, as well as correlated cranial base morphological and clinical traits. Conclusions Our results implicate several strong biological candidates warranting further investigation from the dura expression analysis and also identified a blood gene expression profile corresponding to a global down-regulation in protein synthesis.
    BMC Medical Genomics 06/2014; 7(1):39. DOI:10.1186/1755-8794-7-39 · 3.91 Impact Factor
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    ABSTRACT: This study described the cerebrospinal fluid (CSF) exposure of vancomycin in 8 children prescribed intravenous vancomycin therapy for cerebral ventricular shunt infection. Vancomycin CSF concentrations ranged from 0.03 to 9.13 mg/L and the CSF: plasma ratio ranged from 0 to 0.66. Two children out of three with a staphylococcal CSF infection had CSF concentrations > minimal inhibitory concentration at the end of the dosing interval.
    The Pediatric Infectious Disease Journal 04/2014; 33(10). DOI:10.1097/INF.0000000000000385 · 3.14 Impact Factor
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    ABSTRACT: OBJECTIVES Mild traumatic brain injury (mTBI) is linked to neurodegenerative disease found in military veterans and athletes. mTBI is thought to be caused by head acceleration during impact, but specific tolerable acceleration levels remain unclear. Animal studies suggest that acceleration tolerance varies substantially in different anatomical directions. However, directional sensitivity in humans is unknown due to subjective neurological outcomes and lack of head acceleration measurements during injury in all linear and rotational directions (i.e. six-degrees-of-freedom or 6-DOF). Our objective was to measure injury and non-injury human head impacts in 6-DOF to determine if the human brain's tolerance to injury is direction-dependent. METHODS Novel instrumented mouthguards were used to measure head impact acceleration at American Football games and practices, boxing sparring sessions, and mixed martial arts sparring sessions and match. 6-DOF measurements were acquired using a tri-axial accelerometer (translation in anterior, left, and superior directions), and a tri-axial gyroscope (rotation in coronal, sagittal, and horizontal planes). Impacts recorded by the mouthguards were confirmed by video. Common kinematic measures implicated in head injury were computed: maximum linear acceleration, Head Injury Criterion (HIC), maximum rotational acceleration, and change in rotational velocity. These measures were compared by direction as well as by vector magnitude (L 2-norm). Injury was diagnosed by sideline/ringside clinicians. RESULTS
    10th World Congress on Brain Injury, San Francisco, California, USA; 03/2014
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    ABSTRACT: Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant.
    Cancer cell 03/2014; 25(3):393-405. DOI:10.1016/j.ccr.2014.02.004 · 23.89 Impact Factor
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    ABSTRACT: Plasmonics-active gold nanostars exhibiting strong imaging contrast and efficient photothermal transduction were synthesized for a novel pulsed laser-modulated plasmonics-enhanced brain tumor microvascular permeabilization. We demonstrate a selective, optically modulated delivery of nanoprobes into the tumor parenchyma with minimal off-target distribution.
    Nanoscale 03/2014; DOI:10.1039/c3nr06770j · 7.39 Impact Factor
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    ABSTRACT: Nanotechnology provides tremendous biomedical opportunities for cancer diagnosis, imaging, and therapy. In contrast to conventional chemotherapeutic agents where their actual target delivery cannot be easily imaged, integrating imaging and therapeutic properties into one platform facilitates the understanding of pharmacokinetic profiles, and enables monitoring of the therapeutic process in each individual. Such a concept dubbed "theranostics" potentiates translational research and improves precision medicine. One particular challenging application of theranostics involves imaging and controlled delivery of nanoplatforms across blood-brain-barrier (BBB) into brain tissues. Typically, the BBB hinders paracellular flux of drug molecules into brain parenchyma. BBB disrupting agents (e.g. mannitol, focused ultrasound), however, suffer from poor spatial confinement. It has been a challenge to design a nanoplatform not only acts as a contrast agent but also improves the BBB permeation. In this study, we demonstrated the feasibility of plasmonic gold nanoparticles as both high-resolution optical contrast agent and focalized tumor BBB permeation-inducing agent. We specifically examined the microscopic distribution of nanoparticles in tumor brain animal models. We observed that most nanoparticles accumulated at the tumor periphery or perivascular spaces. Nanoparticles were present in both endothelial cells and interstitial matrices. This study also demonstrated a novel photothermal-induced BBB permeation. Fine-tuning the irradiating energy induced gentle disruption of the vascular integrity, causing short-term extravasation of nanomaterials but without hemorrhage. We conclude that our gold nanoparticles are a powerful biocompatible contrast agent capable of inducing focal BBB permeation, and therefore envision a strong potential of plasmonic gold nanoparticle in future brain tumor imaging and therapy.
    Proceedings of SPIE - The International Society for Optical Engineering 01/2014; DOI:10.1117/12.2040960 · 0.20 Impact Factor
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    ABSTRACT: Chiari Type I Malformation (CMI) is characterized by herniation of the cerebellar tonsils through the base of the skull. Although cerebellar tonsillar herniation (CTH) is hypothesized to result from an underdeveloped posterior cranial fossa (PF), patients are frequently diagnosed by the extent of CTH without cranial morphometric assessment. We recently completed the largest CMI whole genome qualitative linkage screen to date. Despite an initial lack of statistical evidence, stratified analyses using clinical criteria to reduce heterogeneity resulted in a striking increase in evidence for linkage. The present study focused on the use of cranial base morphometrics to further dissect this heterogeneity and increase power to identify disease genes. We characterized the genetic contribution for a series of PF traits and evaluated the use of heritable, disease-relevant PF traits in ordered subset analysis (OSA). Consistent with a genetic hypothesis for CMI, much of the PF morphology was found to be heritable and multiple genomic regions were strongly implicated from OSA, including regions on Chromosomes 1 (LOD = 3.07, p = 3 × 10(-3) ) and 22 (LOD = 3.45, p = 6 × 10(-5) ) containing several candidates warranting further investigation. This study underscores the genetic heterogeneity of CMI and the utility of PF traits in CMI genetic studies.
    Annals of Human Genetics 01/2014; 78(1):1-12. DOI:10.1111/ahg.12041 · 1.93 Impact Factor
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    ABSTRACT: The cerebral organization of language in epilepsy patients has been studied with invasive procedures such as Wada testing and electrical cortical stimulation mapping and more recently with noninvasive neuroimaging techniques, such as functional MRI. In the setting of a chronic seizure disorder, clinical variables have been shown to contribute to cerebral language reorganization underscoring the need for language lateralization and localization procedures. We present a 14-year-old pediatric patient with a refractory epilepsy disorder who underwent two neurosurgical resections of a left frontal epileptic focus separated by a year. He was mapped extraoperatively through a subdural grid using cortical stimulation to preserve motor and language functions. The clinical history and extensive workup prior to surgery is discussed as well as the opportunity to compare the cortical maps for language, motor, and sensory function before each resection. Reorganization in cortical tongue sensory areas was seen concomitant with a new zone of ictal and interictal activity in the previous tongue sensory area. Detailed neuropsychological data is presented before and after any surgical intervention to hypothesize about the extent of reorganization between epochs. We conclude that intrahemispheric cortical plasticity does occur following frontal lobe resective surgery in a teenager with medically refractory seizures.
    11/2013; 3(4):1597-1614. DOI:10.3390/brainsci3041597
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    ABSTRACT: Effective treatment of patients with malignant brain tumors requires surgical resection of a high percentage of the bulk tumor. Surgeons require a method that enables delineation of tumor margins, which are not visually distinct by eye. In this study, the feasibility of using gold nanorods (GNRs) for this purpose is evaluated. Anti-Epidermal Growth Factor Receptor (anti-EGFR) conjugated GNRs are used to label human xenograft glioblastoma multiforme (GBM) tumors embedded within slices of brain tissues from healthy nude mice. The anti-EGFR GNRs exhibit enhanced absorption at red to near-infrared wavelengths, often referred to as the tissue optical window, where absorption from blood is minimal. To enable definition of molecular specificity and spatial accuracy of the label, the GNR absorption is compared with GFP fluorescence which is expressed by the GBM cells used here. This work demonstrates a simple but highly translational technique to classify normal and malignant brain tissue regions in open surgery applications using immunolabeled GNR contrast agents.
    Biomedical Optics Express 11/2013; 4(11):2284-2295. DOI:10.1364/BOE.4.002284 · 3.50 Impact Factor
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    ABSTRACT: Medulloblastoma (MB) is the most common malignant brain tumor in children. While aggressive surgery, radiation, and chemotherapy have improved outcomes, survivors suffer severe long-term side effects, and many patients still succumb to their disease. For patients whose tumors are driven by mutations in the Sonic hedgehog (SHH) pathway, SHH antagonists offer some hope. However, many SHH-associated MBs do not respond to these drugs, and those that do may develop resistance. Therefore, more effective treatment strategies are needed for both SHH and non-SHH-associated MB. One such strategy involves targeting the cells that are critical for maintaining tumor growth, known as tumor-propagating cells (TPCs). We previously identified a population of TPCs in tumors from patched mutant mice, a model for SHH-dependent MB. These cells express the surface antigen CD15/SSEA-1 and have elevated levels of genes associated with the G2/M phases of the cell cycle. Here, we show that CD15+ cells progress more rapidly through the cell cycle than CD15- cells and contain an increased proportion of cells in G2/M, suggesting that they might be vulnerable to inhibitors of this phase. Indeed, exposure of tumor cells to inhibitors of Aurora and Polo-like kinases, key regulators of G2/M, induces cell cycle arrest, apoptosis and enhanced sensitivity to conventional chemotherapy. Moreover, treatment of tumor-bearing mice with these agents significantly inhibits tumor progression. Importantly, cells from human patient-derived MB xenografts are also sensitive to Aurora and Polo-like kinase inhibitors. Our findings suggest that targeting G2/M regulators may represent a novel approach for treatment of human MB.
    Cancer Research 09/2013; 73(20). DOI:10.1158/0008-5472.CAN-12-4258 · 9.28 Impact Factor

Publication Stats

674 Citations
392.99 Total Impact Points

Institutions

  • 2013–2015
    • Stanford University
      • Department of Neurosurgery
      Palo Alto, California, United States
  • 2007–2015
    • Duke University
      • Department of Surgery
      Durham, North Carolina, United States
  • 2014
    • Lucile Packard Children’s Hospital at Stanford
      Palo Alto, California, United States
  • 2008–2014
    • Duke University Medical Center
      • • Division of Neurosurgery
      • • Department of Surgery
      • • Division of Pediatric General Surgery
      Durham, North Carolina, United States