Genomes and Genes
Summary: Primary or metastatic neoplasms of the CEREBELLUM. Tumors in this location frequently present with ATAXIA or signs of INTRACRANIAL HYPERTENSION due to obstruction of the fourth ventricle. Common primary cerebellar tumors include fibrillary ASTROCYTOMA and cerebellar HEMANGIOBLASTOMA. The cerebellum is a relatively common site for tumor metastases from the lung, breast, and other distant organs. (From Okazaki & Scheithauer, Atlas of Neuropathology, 1988, p86 and p141)
Publications308 found, 100 shown here
- Curcumin inhibits the Sonic Hedgehog signaling pathway and triggers apoptosis in medulloblastoma cellsMaha H Elamin
Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Mol Carcinog 49:302-14. 2010..This effect was mediated through strong downregulation of Bcl-2. These results indicate that curcumin, a natural nontoxic compound, represents great promise as Shh-targeted therapy for medulloblastomas...
- Medulloblastoma comprises four distinct molecular variantsPaul A Northcott
Hospital for Sick Children, Toronto, Ontario, Canada
J Clin Oncol 29:1408-14. 2011..We studied a large cohort of medulloblastomas to determine how many subgroups of the disease exist, how they differ, and the extent of overlap between subgroups...
- Molecular subgroups of medulloblastoma: the current consensusMichael D Taylor
Division of Neurosurgery, Hospital for Sick Children, University of Toronto, Toronto, Canada
Acta Neuropathol 123:465-72. 2012....
- The genetic landscape of the childhood cancer medulloblastomaD Williams Parsons
Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
Science 331:435-9. 2011....
- Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcomeYoon Jae Cho
Children s Hospital Boston, Boston, MA 02115, USA
J Clin Oncol 29:1424-30. 2011....
- Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological featuresMarcel Kool
Department of Human Genetics, Academic Medical Center, Amsterdam, The Netherlands
PLoS ONE 3:e3088. 2008..This illustrates the potential benefits of a robust classification of medulloblastoma patients and a detailed knowledge of associated biological mechanisms...
- Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomasMarcel Kool
Division of Pediatric Neurooncology, German Cancer Research Center DKFZ, Heidelberg, Germany
Acta Neuropathol 123:473-84. 2012..Results from these analyses will form the basis for prospective multi-center studies and will have an impact on how the different subgroups of medulloblastoma will be treated in the future...
- Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449Charles M Rudin
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA
N Engl J Med 361:1173-8. 2009....
- Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterationsMargaret C Thompson
St Jude Children s Research Hospital, Memphis, TN 38105, USA
J Clin Oncol 24:1924-31. 2006..We hypothesized that gene expression profiling might be a more rapid and cost-effective method of identifying tumors that contain specific genetic abnormalities...
- Subtypes of medulloblastoma have distinct developmental originsPaul Gibson
Department of Developmental Neurobiology, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA
Nature 468:1095-9. 2010..Our data provide an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer...
- Mutations in SUFU predispose to medulloblastomaMichael D Taylor
Division of Neurosurgery, The Arthur and Sonia Labatt Brain Tumour Research Centre, Toronto, Canada
Nat Genet 31:306-10. 2002..SUFU is a newly identified tumor-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway through a newly identified mechanism...
- Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastomaPaul A Northcott
Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Toronto, Ontario, Canada
Nat Genet 41:465-72. 2009....
- Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trialAmar Gajjar
Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
Lancet Oncol 7:813-20. 2006..We aimed to investigate the effectiveness of risk-adapted radiotherapy followed by a shortened period of dose-intense chemotherapy in children with medulloblastoma...
- Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroupsDavid W Ellison
Department of Pathology MS 250, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA
Acta Neuropathol 121:381-96. 2011....
- Altered neural cell fates and medulloblastoma in mouse patched mutantsL V Goodrich
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305 5427, USA
Science 277:1109-13. 1997..Mice heterozygous for the ptc mutation were larger than normal, and a subset of them developed hindlimb defects or cerebellar medulloblastomas, abnormalities also seen in BCNS patients...
- Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitinationLucia Di Marcotullio
Department of Experimental Medicine and Pathology, University La Sapienza, Roma, 324 Viale Regina Elena, 00161 Roma, Italy
Nat Cell Biol 8:1415-23. 2006..This novel Numb-dependent regulatory loop may limit the extent and duration of Hedgehog signalling during neural-progenitor differentiation, and its subversion may be a relevant event in brain tumorigenesis...
- YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferationAfrica Fernandez-L
Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
Genes Dev 23:2729-41. 2009..Post-irradiation, YAP1 was found in newly growing tumor cells. These findings implicate YAP1 as a new Shh effector that may be targeted by medulloblastoma therapies aimed at eliminating medulloblastoma recurrence...
- Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastomaRoger J Packer
Division of Neurology, Children s National Medical Center, Washington, DC 20010, USA
J Clin Oncol 24:4202-8. 2006..To determine the event-free survival (EFS) and overall survival of children with average-risk medulloblastoma and treated with reduced-dose craniospinal radiotherapy (CSRT) and one of two postradiotherapy chemotherapies...
- p27(Kip1), a double-edged sword in Shh-mediated medulloblastoma: Tumor accelerator and suppressorBobby Bhatia
Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Cell Cycle 9:4307-14. 2010..Together, our data indicate that the dosage of p27(Kip1) plays a role in cell cycle progression and tumor suppression in Shh-mediated medulloblastoma expansion...
- Medulloblastoma: developmental mechanisms out of controlSilvia Marino
Institute of Clinical Pathology, University Hospital, Schmelzbergstrasse 12, 8091 Zurich, Switzerland
Trends Mol Med 11:17-22. 2005..Recent advances in the understanding of the role of Sonic Hedgehog, Wnt and Notch signalling pathways in the development of the cerebellum have shed new light on medulloblastoma pathogenesis...
- Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinctPaul A Northcott
The Arthur and Sonia Labatt Brain Tumour Research Center, Hospital for Sick Children, Toronto, ON, Canada
Acta Neuropathol 122:231-40. 2011..Collectively, our data demonstrate that pediatric and adult Shh-medulloblastomas are clinically, transcriptionally, genetically, and prognostically distinct...
- Definition of disease-risk stratification groups in childhood medulloblastoma using combined clinical, pathologic, and molecular variablesDavid W Ellison
Department of Pathology MS 250, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA
J Clin Oncol 29:1400-7. 2011..Developing a practical therapeutic stratification that allows accurate identification of disease risk offers the potential to individualize adjuvant therapy and to minimize long-term adverse effects in a subgroup of survivors...
- Silencing of thrombospondin-1 is critical for myc-induced metastatic phenotypes in medulloblastomaLimei Zhou
Sonia and Arthur Labatt Brain Tumor Research Centre, Hospital for Sick Children, University Avenue, Toronto, Ontario, Canada M5G 1X8
Cancer Res 70:8199-210. 2010..These findings indicate the Myc-regulatory network targets Tsp-1 via multiple mechanisms in medulloblastoma transformation, and highlight a novel critical role for Tsp-1 in Myc-mediated aggressive medulloblastoma phenotypes...
- Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN lociStefan Pfister
Division of Molecular Genetics and Biostatistics and Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
J Clin Oncol 27:1627-36. 2009..Medulloblastoma is the most common malignant brain tumor in children. Current treatment decisions are based on clinical variables. Novel tumor-derived biomarkers may improve the risk stratification of medulloblastoma patients...
- The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau diseaseJohn E Wanebo
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892 1414, USA
J Neurosurg 98:82-94. 2003....
- Heterogeneity of familial medulloblastoma and contribution of germline PTCH1 and SUFU mutations to sporadic medulloblastomaIngrid Slade
Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
Fam Cancer 10:337-42. 2011....
- TP53 mutation is frequently associated with CTNNB1 mutation or MYCN amplification and is compatible with long-term survival in medulloblastomaElke Pfaff
German Cancer Research Center, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany
J Clin Oncol 28:5188-96. 2010..A recent report identified TP53 mutations in MB as an adverse prognostic marker. Hence, the current study was conducted to validate the prognostic role of TP53 mutation in MB and to understand its contribution to tumorigenesis...
- Prediction of central nervous system embryonal tumour outcome based on gene expressionScott L Pomeroy
Division of Neuroscience, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 415:436-42. 2002..We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis...
- Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: The International Society of Paediatric Oncology/United Kingdom Children's Cancer Study Group PNET-3 StudyRoger E Taylor
Cookridge Hospital, Leeds, West Yorkshire, LS16 6QB, United Kingdom
J Clin Oncol 21:1581-91. 2003..Chemotherapy comprised vincristine 1.5 mg/m2 weekly for 10 weeks and four cycles of etoposide 100 mg/m2 daily for 3 days, and carboplatin 500 mg/m2 daily for 2 days alternating with cyclophosphamide 1.5 g/m2...
- Somatic mutations of WNT/wingless signaling pathway components in primitive neuroectodermal tumorsA Koch
Department of Neuropathology, University of Bonn Medical Center; Bonn, Germany
Int J Cancer 93:445-9. 2001..Our data indicate that inappropriate activation of the WNT/wingless signaling pathway by mutations of its components may contribute to the pathogenesis of a subset of PNETs...
- Hyperfractionated versus conventional radiotherapy followed by chemotherapy in standard-risk medulloblastoma: results from the randomized multicenter HIT-SIOP PNET 4 trialBirgitta Lannering
Department of Pediatrics, University of Gothenburg, The Queen Silvia Children s Hospital, S 41685 Göteborg, Sweden
J Clin Oncol 30:3187-93. 2012....
- GDC-0449-a potent inhibitor of the hedgehog pathwayKirk D Robarge
Genentech, Small Molecule Drug Discovery 1 DNA Way, South San Francisco, CA 94080, United States
Bioorg Med Chem Lett 19:5576-81. 2009..5mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials, where it is initially being evaluated for the treatment of BCC...
- Cerebellum development and medulloblastomaMartine F Roussel
Department of Tumor Cell Biology and Genetics, St Jude Children s Research Hospital, Memphis, Tennessee, USA
Curr Top Dev Biol 94:235-82. 2011..In this chapter, we will review the development of the cerebellar cortex, highlighting signaling pathways of potential relevance to tumorigenesis...
- MicroRNA-182 promotes leptomeningeal spread of non-sonic hedgehog-medulloblastomaAlfa H C Bai
Division of Molecular Genetics B060, German Cancer Research Center DKFZ, Heidelberg, Germany
Acta Neuropathol 123:529-38. 2012..We therefore reason that targeted inhibition of miR-182 may prevent leptomeningeal spread in patients with non-SHH-MB...
- Subgroup-specific structural variation across 1,000 medulloblastoma genomesPaul A Northcott
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada
Nature 488:49-56. 2012..Numerous targetable SCNAs, including recurrent events targeting TGF-Î² signalling in Group 3, and NF-ÎºB signalling in Group 4, suggest future avenues for rational, targeted therapy...
- Development and cancer of the cerebellumMary E Hatten
Laboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10065, USA
Trends Neurosci 34:134-42. 2011..A better understanding of the developmental origins of these tumors will have significant implications for enhancing the treatment of this important childhood cancer...
- The miR-17/92 polycistron is up-regulated in sonic hedgehog-driven medulloblastomas and induced by N-myc in sonic hedgehog-treated cerebellar neural precursorsPaul A Northcott
Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Cancer Res 69:3249-55. 2009..We conclude that miR-17/92 is a positive effector of Shh-mediated proliferation and that aberrant expression/amplification of this miR confers a growth advantage to medulloblastomas...
- Cerebellar stem cells act as medulloblastoma-initiating cells in a mouse model and a neural stem cell signature characterizes a subset of human medulloblastomasR Sutter
Neuroscience Centre, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK
Oncogene 29:1845-56. 2010..Furthermore, the expression of these markers identified a subset of human medulloblastomas associated with a poorer clinical outcome...
- Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma developmentHaotian Zhao
Departments of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
Genes Dev 22:722-7. 2008..Genes regulating the BMP signaling pathway are down-regulated in mouse MBs. Thus, BMPs are potent inhibitors of MB and should be considered as novel therapeutic agents...
- Management of and prognosis with medulloblastoma: therapy at a crossroadsRoger J Packer
Division of Neurology, Children s National Medical Center, Washington, DC 20010, USA
Arch Neurol 65:1419-24. 2008..However, these biological advances have yet to be integrated into the treatment of medulloblastoma in children or adults...
- Small molecule inhibition of GDC-0449 refractory smoothened mutants and downstream mechanisms of drug resistanceGerrit J P Dijkgraaf
Department of Molecular Biology, Genentech Inc, South San Francisco, California 94080, USA
Cancer Res 71:435-44. 2011..Importantly, these HPI resistant MB allografts retained their sensitivity to PI3K inhibition, presenting additional opportunities for the treatment of such tumors...
- Medulloblastoma growth inhibition by hedgehog pathway blockadeDavid M Berman
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Science 297:1559-61. 2002....
- Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastomaTrudy G Oliver
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
Development 132:2425-39. 2005..The identification and molecular characterization of pre-neoplastic cells provides insight into the early steps in medulloblastoma formation, and may yield important markers for early detection and therapy of this disease...
- An investigation of WNT pathway activation and association with survival in central nervous system primitive neuroectodermal tumours (CNS PNET)H A Rogers
Children s Brain Tumour Research Centre, Queen s Medical Centre, University of Nottingham, D Floor Medical School D32, Nottingham, UK
Br J Cancer 100:1292-302. 2009..The results suggest that the WNT/beta-catenin pathway plays an important role in the pathogenesis of CNS PNETs. However, activation is not caused by mutations in CTNNB1 or APC in the majority of CNS PNET cases...
- Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cellsWolfgang Hartmann
Department of Neuropathology, University of Bonn Medical Center, Sigmund Freud St 25, D 53105 Bonn, Germany
Am J Pathol 166:1153-62. 2005..Together, our data point to an important role of IGF-II for the proliferation control of both cerebellar neural precursors and MB cells...
- Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effectorJynho Kim
Department of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA
Proc Natl Acad Sci U S A 107:13432-7. 2010....
- A clinicobiological model predicting survival in medulloblastomaAmit Ray
Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada
Clin Cancer Res 10:7613-20. 2004..The purpose of this study was to determine the relative contributions of biological and clinical predictors of survival in patients with medulloblastoma (MB)...
- Childhood medulloblastoma: novel approaches to the classification of a heterogeneous diseaseDavid W Ellison
Department of Pathology, St Jude Children s Research Hospital, Memphis, TN 38103, USA
Acta Neuropathol 120:305-16. 2010....
- Inhibition of STAT3 expression and signaling in resveratrol-differentiated medulloblastoma cellsLi Jun Yu
Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, 116044 Dalian, PR China
Neoplasia 10:736-44. 2008..This signaling may be the major target of resveratrol. Enhanced leukemia inhibitory factor and Bcl-2 expressions in resveratrol-treated cells might reflect a compensatory response to the loss of STAT3 function...
- Medulloblastoma: tumorigenesis, current clinical paradigm, and efforts to improve risk stratificationWilliam R Polkinghorn
Massachusetts General Hospital, Boston, MA 02114, USA
Nat Clin Pract Oncol 4:295-304. 2007..These efforts include identifying histopathologic, cytogenetic, and molecular features that may correlate with prognosis...
- Long-term follow-up of pediatric benign cerebellar astrocytomasHideki Ogiwara
Division of Neurosurgery, Children s Memorial Hospital, Chicago, Illinois, USA
Neurosurgery 70:40-7; discussion 47-8. 2012..The long-term prognosis of cerebellar astrocytomas needs to be reviewed...
- Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastomaN Patrik Brodin
Radiation Medicine Research Center, Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Denmark
Acta Oncol 50:806-16. 2011..The aim was also to find dose-volume toxicity parameters relevant to children undergoing RT to be used in the inverse planning of RA and IMPT, and to use in the risk estimations...
- Functional genomics identifies drivers of medulloblastoma disseminationMichael Mumert
Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
Cancer Res 72:4944-53. 2012....
- From childhood to adulthood: long-term outcome of medulloblastoma patients. The Institut Curie experience (1980-2000)P Frange
Department of Paediatric Oncology, Institut Curie, 26 Rue d Ulm, 75005 Paris, France
J Neurooncol 95:271-9. 2009..These findings reinforce the importance of early intervention programs for all survivors in order to reduce the psychosocial impacts of their disease...
- Stemness is only a state of the cellM N Kagalwala
Department of Genetics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
Cold Spring Harb Symp Quant Biol 73:227-34. 2008....
- Spontaneous regression of cerebellar astrocytoma after subtotal resectionPaul Steinbok
Division of Neurosurgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada
Childs Nerv Syst 22:572-6. 2006..In this case, the time course of regression has been well documented. CONCLUSION: The time course of regression may provide clues as to the underlying cause of this phenomenon...
- Comprehensive molecular cytogenetic investigation of chromosomal abnormalities in human medulloblastoma cell lines and xenograftNaji Aldosari
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
Neuro Oncol 4:75-85. 2002....
- Cerebellar glioblastomas: pathophysiology, clinical presentation and managementGordan Grahovac
Department of Neurosurgery, University Hospital Dubrava, HR 10000 Zagreb, Croatia
Acta Neurochir (Wien) 151:653-7. 2009..We report a 28 year old patient with primary multi-focal cerebellar glioblastoma multiforme and review the pathophysiology, clinical presentation, diagnosis and treatment of cerebellar glioblastomas...
- An animal model of MYC-driven medulloblastomaYanxin Pei
Tumor Development Program, NCI Designated Cancer Center, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
Cancer Cell 21:155-67. 2012..These findings suggest that cerebellar stem cells can give rise to MYC-driven MB and identify a novel model that can be used to test therapies for this devastating disease...
- Advantage of protons compared to conventional X-ray or IMRT in the treatment of a pediatric patient with medulloblastomaW H St Clair
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Int J Radiat Oncol Biol Phys 58:727-34. 2004..To compare treatment plans from standard photon therapy to intensity modulated X-rays (IMRT) and protons for craniospinal axis irradiation and posterior fossa boost in a patient with medulloblastoma...
- The RNA-binding protein Musashi1 affects medulloblastoma growth via a network of cancer-related genes and is an indicator of poor prognosisDat T Vo
Greehey Children s Cancer Research Institute, University of Texas Health Science Center, San Antonio, USA
Am J Pathol 181:1762-72. 2012..Our results suggest that Msi1 functions as a regulator of multiple processes in medulloblastoma formation and could become an important therapeutic target...
- Rapid diagnosis of medulloblastoma molecular subgroupsEd C Schwalbe
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
Clin Cancer Res 17:1883-94. 2011..Microarray studies indicate medulloblastoma comprises distinct molecular disease subgroups, which offer potential for improved clinical management...
- Neurocognitive consequences of risk-adapted therapy for childhood medulloblastomaRaymond K Mulhern
Division of Behavioral Medicine, Department of Biostatistics, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
J Clin Oncol 23:5511-9. 2005....
- Transient inhibition of the Hedgehog pathway in young mice causes permanent defects in bone structureHiromichi Kimura
Department of Developmental Neurobiology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA
Cancer Cell 13:249-60. 2008..After drug removal, osteoblasts invaded the cartilage plate, mineralization occurred, and there was premature fusion of the growth plate resulting in permanent disruption of bone epiphyses...
- Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques?Catherine T Lee
Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
Int J Radiat Oncol Biol Phys 63:362-72. 2005....
- Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridizationNaoki Yokota
The Arthur and Sonia Labatt Brain Tumor Research Centre, The University of Toronto, Toronto, Ontario, Canada
Oncogene 23:3444-53. 2004..This study has revealed a panel of developmentally regulated genes that may be involved in the pathogenesis of MB...
- Progress and challenges in childhood brain tumorsRoger J Packer
Center for Neuroscience and Behavioral Medicine, USA
J Neurooncol 75:239-42. 2005....
- Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology StudyV Oyharcabal-Bourden
Institut Curie, Paris, France
J Clin Oncol 23:4726-34. 2005..The primary objective of this study was to decrease the late effects of prophylactic radiation without reducing survival in standard-risk childhood medulloblastoma...
- A mouse model of the most aggressive subgroup of human medulloblastomaDaisuke Kawauchi
Department of Tumor Cell Biology, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA
Cancer Cell 21:168-80. 2012..This mouse model should significantly accelerate understanding and treatment of the most aggressive form of medulloblastoma and infers distinct roles for MYC and MYCN in tumorigenesis...
- RASSF1A and the BH3-only mimetic ABT-737 promote apoptosis in pediatric medulloblastoma cell linesJane Levesley
Children s Brain Tumour Research Centre, Queen s Medical Centre, Medical School, Nottingham University, Nottingham NG7 2UH, UK
Neuro Oncol 13:1265-76. 2011..Investigation of its mechanism of action has revealed that these pathways can still be promoted in its absence and how these potentially represent novel therapeutic targets for medulloblastoma...
- Distinctive clinical course and pattern of relapse in adolescents with medulloblastomaUri Tabori
Pediatric Brain Tumor Program, The Hospital for Sick Children, Toronto, and Department of Hematology Oncology, McMaster University, Hamilton, Ontario, Canada
Int J Radiat Oncol Biol Phys 64:402-7. 2006..To report the clinical course of adolescents with medulloblastoma, with specific emphasis on prognosis and pattern of relapse...
- Predicting relapse in patients with medulloblastoma by integrating evidence from clinical and genomic featuresPablo Tamayo
Eli and Edythe Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA
J Clin Oncol 29:1415-23. 2011..We also introduce a novel Bayesian nomogram indicating the amount of evidence that each feature contributes on a patient-by-patient basis...
- Molecular analysis of PinX1 in medulloblastomasQing Chang
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
Int J Cancer 109:309-14. 2004..Taken together, our results suggest that PinX1 does not play a major role in the oncogenesis of medulloblastomas...
- VMY-1-103 is a novel CDK inhibitor that disrupts chromosome organization and delays metaphase progression in medulloblastoma cellsLymor Ringer
Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center Washington DC, USA
Cancer Biol Ther 12:818-26. 2011..Our data suggest that VMY-1-103 possesses unique antiproliferative capabilities and that this compound may form the basis of a new candidate drug to treat medulloblastoma...
- Low-level copy number changes of MYC genes have a prognostic impact in medulloblastomaKarel Zitterbart
Department of Pediatric Oncology, University Hospital Brno, Masaryk University, Cernopolni 9, 613 00 Brno, Czech Republic
J Neurooncol 102:25-33. 2011..Our data illustrate the importance of further investigations in multicenter trials to better refine the emerging genomic-based prognostic stratification in MB...
- Correlation of neurosurgical subspecialization with outcomes in children with malignant brain tumorsA L Albright
Department of Neurosurgery, Children s Hospital of Pittsburgh, Pennsylvania, USA
Neurosurgery 47:879-85; discussion 885-7. 2000..This study was performed to evaluate the association between the type of neurosurgeon (general or pediatric) and either the extent of tumor removal or the frequency of complications in children undergoing malignant brain tumor resections...
- Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastomaFrank Mendrzyk
Division of Molecular Genetics B060, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
J Clin Oncol 23:8853-62. 2005..Identification of molecular markers for prognosis and development of novel pathogenesis-based therapies depends crucially on a better understanding of medulloblastoma pathomechanisms...
- OTX2 is critical for the maintenance and progression of Shh-independent medulloblastomasDavid C Adamson
Department of Surgery, The Pediatric Brain Tumor Foundation Institute, and The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Veterans Affairs Medical Center, Durham, North Carolina 27710, USA
Cancer Res 70:181-91. 2010..Mechanistic investigations revealed upregulation of MYC as a potential mechanism whereby OTX2 promotes tumor progression. Our findings define OTX2 as an important oncogenic driver in medulloblastoma...
- Genetic alterations in childhood medulloblastoma analyzed by comparative genomic hybridizationErna M C Michiels
Department of Pediatric Oncology, Emma Kinderziekenhuis Academic Medical Center, Amsterdam, The Netherlands
J Pediatr Hematol Oncol 24:205-10. 2002..Previous reports on the relation between 17q gain and survival could not be confirmed, whereas amplification of N-myc or L-myc seems to indicate poor clinical outcome...
- Sonic Hedgehog signaling impairs ionizing radiation-induced checkpoint activation and induces genomic instabilityJennifer M Leonard
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
J Cell Biol 183:385-91. 2008..These results suggest that inappropriate Shh pathway activation promotes tumorigenesis by disabling a key signaling pathway that helps maintain genomic stability and inhibits tumorigenesis...
- REN(KCTD11) is a suppressor of Hedgehog signaling and is deleted in human medulloblastomaLucia Di Marcotullio
Department of Experimental Medicine and Pathology, University La Sapienza, 324 Viale Regina Elena, 00161 Rome, Italy
Proc Natl Acad Sci U S A 101:10833-8. 2004..Therefore, we identify REN(KCTD11) as a suppressor of Hedgehog signaling and suggest that its inactivation might lead to a deregulation of the tumor-promoting Hedgehog pathway in medulloblastoma...
- Treatment of high risk medulloblastomas in children above the age of 3 years: a SFOP studyJ Verlooy
Department of Paediatric Oncology, Institut Curie, Service d Oncologie Pediatrique, 26 Rue d Ulm, 75231 Paris Cedex 05, France
Eur J Cancer 42:3004-14. 2006..Improvement of EFS of children older than 3 years with high risk medulloblastoma...
- Insulin-like growth factor 2 is required for progression to advanced medulloblastoma in patched1 heterozygous miceRyan B Corcoran
Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA
Cancer Res 68:8788-95. 2008..Exogenous Igf2 protein promoted proliferation of MB precursor cells (GNP) and a MB cell line, PZp53(MED). Blocking igf2 signaling inhibited growth of PZp53(MED) cells, implicating igf2 as a potential clinical target...
- Reducing toxicity from craniospinal irradiation: using proton beams to treat medulloblastoma in young childrenGrace E Yuh
Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California 92354, USA
Cancer J 10:386-90. 2004..We report on a radiation treatment technique that has reduced the dose to critical normal structures in children with medulloblastoma...
- Spontaneous regression of residual low-grade cerebellar pilocytic astrocytomas in childrenRoxana S Gunny
Department of Radiology, Great Ormond Street Hospital for Sick Children, London, UK
Pediatr Radiol 35:1086-91. 2005..Cerebellar low-grade astrocytomas (CLGAs) of childhood are benign tumours and are usually curable by surgical resection alone or combined with adjuvant radiotherapy...
- Two tumor suppressors, p27Kip1 and patched-1, collaborate to prevent medulloblastomaOlivier Ayrault
Department of Genetics and Tumor Cell Biology, Mail Stop no 350, 262 Danny Thomas Place, Memphis, TN 38105 3678, USA
Mol Cancer Res 7:33-40. 2009..In this respect, this mouse medulloblastoma model recapitulates the vast majority of human medulloblastomas that do not sustain TP53 mutations and are not aneuploid...
- Expression of Gli1 and PARP1 in medulloblastoma: an immunohistochemical study of 65 casesJoze Pizem
Medical Faculty, Institute of Pathology, University of Ljubljana, 1000 Ljubljana, Slovenia
J Neurooncol 103:459-67. 2011..In some medulloblastomas, both SHH and WNT appear to be activated. PARP1 is highly expressed in medulloblastomas. It might be useful as a target to increase the effectiveness of current treatment modalities...
- Regulation of cell cycle genes and induction of senescence by overexpression of OTX2 in medulloblastoma cell linesJens Bunt
Department of Human Genetics, Academic Medical Center, Amsterdam, The Netherlands
Mol Cancer Res 8:1344-57. 2010..Our data indicate that OTX2 directly induces a series of cell cycle genes but requires cooperating genes for an oncogenic acceleration of the cell cycle...
- Combining gene expression profiles and clinical parameters for risk stratification in medulloblastomasAna Fernandez-Teijeiro
Division of Neuroscience, Department of Neurology, Department of Medicine, Children s Hospital, 300 Longwood Ave, Boston MA 02115, USA
J Clin Oncol 22:994-8. 2004..Outcome predictions on the basis of microarray gene expression profiles have been the most accurate to date. We ask in a multivariate model whether clinical parameters enhance survival predictions of gene expression profiles...
- Reactivation of death receptor 4 (DR4) expression sensitizes medulloblastoma cell lines to TRAILDolly G Aguilera
Department of Pediatrics, University of Texas, M D Anderson Cancer Center, Houston, 77030, USA
J Neurooncol 93:303-18. 2009....
- All-trans-retinoic acid-induced apoptosis in human medulloblastoma: activation of caspase-3/poly(ADP-ribose) polymerase 1 pathwayKiranmai Gumireddy
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA
Clin Cancer Res 9:4052-9. 2003....
- Crosstalk between medulloblastoma cells and endothelium triggers a strong chemotactic signal recruiting T lymphocytes to the tumor microenvironmentVita S Salsman
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, United States of America
PLoS ONE 6:e20267. 2011..This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications...
- The antiretroviral nucleoside analogue Abacavir reduces cell growth and promotes differentiation of human medulloblastoma cellsAlessandra Rossi
Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia PA
Int J Cancer 125:235-43. 2009..Thus, using Abacavir, alone or in combination with current therapies, might be an effective therapeutic strategy for the treatment of medulloblastoma...
- Adult and pediatric medulloblastomas are genetically distinct and require different algorithms for molecular risk stratificationAndrey Korshunov
Clinical Cooperation Unit Neuropathology, Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany
J Clin Oncol 28:3054-60. 2010..We aimed to identify genetic aberrations in 146 adult MBs to evaluate age-dependent differences in tumor biology and adapt age-specific risk stratification models...
- Stratification of medulloblastoma on the basis of histopathological gradingFelice Giangaspero
Department of Experimental Medicine and Pathology, University of Rome La Sapienza, 00151, Rome, Italy
Acta Neuropathol 112:5-12. 2006..These findings indicate that degree of anaplasia is the most significant histologic feature predictive of the survival of medulloblastoma patients...
- Curcumin (diferuloylmethane) induces apoptosis and blocks migration of human medulloblastoma cellsMadhavi Latha Yadav Bangaru
Division of Endocrinology, Metabolism and Clinical Nutrition, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Anticancer Res 30:499-504. 2010..Furthermore, curcumin down-regulated bcl-2 and bcl(x)l, leading to caspase-mediated cell death. Finally, curcumin blocked migration of MB cells. Thus, we propose developing curcumin as a novel therapeutic agent for MB...
- Gain of 1q is a potential univariate negative prognostic marker for survival in medulloblastomaKen C Lo
Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA
Clin Cancer Res 13:7022-8. 2007..In this context, current strategies for risk assessment, which are based on clinical parameters, remain unsatisfactory...
- Pediatric medulloblastoma: toxicity of current treatment and potential role of protontherapyPiero Fossati
Institute of Radiological Sciences, University of Milan, Milano, Italy
Cancer Treat Rev 35:79-96. 2009....
- Lhermitte-Duclos disease: a report of 31 cases with immunohistochemical analysis of the PTEN/AKT/mTOR pathwayTy W Abel
Department of Pathology, Division of Neuropathology, Johns Hopkins University, Baltimore, Maryland 21287, USA
J Neuropathol Exp Neurol 64:341-9. 2005..These data support recommendations for genetic testing and screening for CD in patients with LDD and suggest a novel therapy for LDD through pharmacologic inhibition of mTOR...
- Cytogenetic evaluation of isochromosome 17q in posterior fossa tumors of children and correlation with clinical outcome in medulloblastoma. Detection of a novel chromosomal abnormalityCarolina DeChiara
Department of Pediatrics, Faculty of Medicine, University Federico II of Naples, Via S Pansini, 5, 80131 Naples, Italy
Childs Nerv Syst 18:380-4. 2002..The purpose of this study was to evaluate the prognostic correlation of this variable, compared with other variables (surgery extent and radiotherapy), with survival...
- Evolution of VHL tumourigenesis in nerve root tissueA O Vortmeyer
Surgical Neurology Branch, National Institute of Neurological Diseases and Stroke, Bethesda, Maryland 20892, USA
J Pathol 210:374-82. 2006..The evolution of frank haemangioblastoma seems to involve multiple steps from a large pool of precursor lesions...
- Nuclear IRS-1-DNA repair and mutagenesis in medulloblastomaKrzysztof Reiss; Fiscal Year: 2012..The proposed studies of DNA repair mechanisms in association with cell signaling pathways are critically important for the development of new therapeutic strategies against malignant dissemination of these cerebellar tumors in CNS. ..
- Identification of a Mitogen for Neuronal Progenitors in the Embryonic CerebellumRobert J Wechsler Reya; Fiscal Year: 2010..In addition, since signals that control growth and differentiation are often dysregulated in cancer, these studies may shed light on the etiology of cerebellar tumors such as medulloblastoma. ..
- CLINICAL RECORDING OF SACCADESA Bahill; Fiscal Year: 1980..We wish to identify the control signal variations the produce these glissades. ..
- Pirfenidone in Children with PNs in NF1Roger Packer; Fiscal Year: 2006..Abstract Not Provided ..
- Myc Signaling in MedulloblastomasCharles Eberhart; Fiscal Year: 2006..Finally, in Specific Aim 4 we propose developing a novel medulloblastoma transgenic model by overexpressing c-Myc in the cerebellum of transgenic mice. ..
- CHILDRENS NATIONAL MEDICAL CENTERRoger Packer; Fiscal Year: 2003....
- Lapatinib in childhood CNS malignanciesMaryam Fouladi; Fiscal Year: 2006..These data will be used in the rational design of future phase I combination or frontline studies to improve the outcome in children with these poor prognosis tumors. [unreadable] [unreadable]..
- Treating CNS malignancies with 131-I-8H9Kim Kramer; Fiscal Year: 2006..abstract_text> ..
- 131-1 3F8 FOR LEPTOMENINGEAL CANCERSKim Kramer; Fiscal Year: 2008..This study will be the basis for other regional therapies using radiolabeled-antibodies targeting tumor associated antigens for other CNS malignancies. [unreadable] [unreadable]..
- Occupational Pesticide Exposure of Parents and Brain Tumor Risk in ChildrenGreta Bunin; Fiscal Year: 2008..The proposed study will provide information on the usefulness of these approaches. [unreadable] [unreadable] [unreadable]..
- PATERNAL EXPOSURE AND SPORADIC BILATERAL RETINOBLASTOMAGreta Bunin; Fiscal Year: 2005..Sporadic heritable RBL is a childhood cancer worth studying in its own right and an ideal model for the investigation of new germline mutation. ..
- CONTROL SELECTION METHODS FOR CHILDHOOD CANCER STUDIESGreta Bunin; Fiscal Year: 2009..A feasible and valid control group is needed to ensure that studies of childhood cancer are scientifically valid and therefore, will provide results that can eventually lead to prevention of these cancers. ..
- GSK-3Beta and Associated Pathways in PNETCorey Raffel; Fiscal Year: 2004..As phosphorylation of Beta-catenin is critical for protein degradation, control of GSK-3Beta activity in PNET will be investigated. ..
- MOLECULAR MECHANISMS OF GRANULE CELL MIGRATIONMARY HATTEN; Fiscal Year: 2007..This information should broaden our view of the mechanisms that control CNS migrations and of the downstream events important to neuronal differentiation within the neural layers. ..
- Control of Cerebellar Development by FGF signalingRobert Wechsler Reya; Fiscal Year: 2008..our understanding of cell cycle regulation in normal granule cell precursors, these studies may shed light on the loss of cell cycle control in medulloblastoma, the most common malignant brain tumor in children [unreadable] [unreadable]..
- Obstructive Sleep Apnea (OSA) in obese teens & preteens: Neurobahavioral effectsDean Beebe; Fiscal Year: 2008..abstract_text> ..
- Invasion and Angiogenesis in Malignant GliomasDavid Zagzag; Fiscal Year: 2008..Results from these experiments will lead to future strategies designed to inhibit specific molecular components implicated in these critical processes. ..
- Systemic perinatal insults disrupt neurodevelopmentShenandoah Robinson; Fiscal Year: 2008..Insights into mechanisms underlying the disruption of perinatal neural development will lead to novel interventions to enhance neural development in neonates, and minimize neurologic deficits. ..
- Multiattribute decision theory for IMRT plan selectionMark Phillips; Fiscal Year: 2009..We will develop and evaluate influence diagrams for prostate cancer and for head &neck cancer. ..
- AML1 in Hematopoietic Cell DevelopmentROBERT LORSBACH; Fiscal Year: 2006..abstract_text> ..
- Hindbrain Herniation in Sheep Model of MyelomeningoceleCornelia von Koch; Fiscal Year: 2002..Furthermore, we will characterize in lambs gross pathological and axonal pathfinding anomalies usually seen in the human disease. ..
- GLYCOSPHINGOLIPIDS IN MURINE NEURODEGENERATIVE DISEASESTHOMAS SEYFRIED; Fiscal Year: 2004..Since there are no effective treatments for human ganglioside storages disease, the proposed research could offer a novel therapy for the early intervention of these neurodegenerative disorders. ..
- GENETICS OF CEREBELLAR AXON FORMATIONMARY HATTEN; Fiscal Year: 2004..In the BAC transgenic animals we can examine the effect of kinase-deficient neurons on the development of the other cerebellar neurons and glia. ..
- CHRONOBIOLOGY OF PARTIAL EPILEPSYMark Quigg; Fiscal Year: 2002..In summary, these studies will provide insight into the chronoblological factors that facilitate partial seizure expression and may provide new perspectives into treatments for poorly controlled partial epilepsy. ..
- PEDIATRIC ONCOLOGY GROUP STUDIESThomas McLean; Fiscal Year: 2002....
- Clinical and Neuropsychological Investigations in Batten DiseaseJonathan W Mink; Fiscal Year: 2010..Although JNCL is a rare disease, our research has implications that can be generalized to the study of other degenerative neurologic disorders in children and for preparing translational clinical trials in these diseases. ..
- Embryonic Development of the CerebellumMARY HATTEN; Fiscal Year: 2007..abstract_text> ..
- Glycosphingolipid Effects on Brain Tumor AngiogenesisTHOMAS SEYFRIED; Fiscal Year: 2006..The proposed research will better define the relationship between gangliosides and tumor angiogenesis and can lead to new experimental strategies for managing brain tumors. ..
- Metabolic effects of brain radiation in childrenAlena Horska; Fiscal Year: 2006..abstract_text> ..
- PATHOPHYSIOLOGY OF CHOREAJonathan Mink; Fiscal Year: 2002..abstract_text> ..
- Phase I/II Study of MS-275 and 5-Azacytidine in Patients with Advanced Non-SmallCHARLES RUDIN; Fiscal Year: 2008..If successful, this approach could alter the poor prognosis of individuals with this disease. [unreadable] [unreadable] [unreadable]..
- GLYCOSPHINGOLIPIDS IN MURINE NEURODEGENERATIVE DISEASESTHOMAS SEYFRIED; Fiscal Year: 2009..The proposed studies will provide essential information on combinatorial therapies for the ganglioside storage diseases and will have translational benefit to the clinic. ..
- A pharmacogenetic and pharmacodynamic study of erlotinibCHARLES RUDIN; Fiscal Year: 2004..Defining the basis of this toxicity could also promote the development of EGFR-directed agents that may avoid such toxicity or that may be effective in a broader spectrum of cancer patients. ..
- CSF-1 RECEPTOR SIGNALLING AND G1 PROGRESSIONMartine Roussel; Fiscal Year: 2001..The identification of novel effector molecules should enable definition of regulatory networks that govern events late in G1 phase, including the commitment to enter S phase. ..
- Actions of Estrogen & Environmental Estrogens on NeuronsScott M Belcher; Fiscal Year: 2010..The ability of ERa, ERp, and the orphan G-protein coupled receptor GPR30 to act as the membrane ER will be directly addressed. ..
- TRICCS: Targeting Inattention in Childhood Cancer SurvivorsKristina Hardy; Fiscal Year: 2008..Further, we predict that increases in working memory and attention from baseline to post-intervention will be of moderate effect size, and will be maintained at 3-month follow-up. [unreadable] [unreadable] [unreadable] [unreadable]..
- Deficits in Facial Expression Recognition in Childhood Cancer SurvivorsMelanie Bonner; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- SUBUNIT ASSEMBLY DOMAINS--TARGETS TO LIMIT NEUROTOXICITYScott Belcher; Fiscal Year: 2002..abstract_text> ..
- Actions of Estrogen & Environmental Estrogens on NeuronsScott Belcher; Fiscal Year: 2004..From these results a neuronal "E2-signature cDNA array" will be developed and used in Aim 3 to determine how environmental estrogens influence E2-responsive gene expression in these developing neurons. ..
- Cellular Immunotherapy for Neuroblastoma With CTL clonesMichael Jensen; Fiscal Year: 2002..4.) To assess in this patient population the development of antibody and cellular immune responses against the scFvFc:zeta and HyTK chimeric proteins. ..
- INVERSE METASTATIC MODALITIES BY HEPARANASESDario Marchetti; Fiscal Year: 2005..They will provide a framework for the development of polysaccharide-based anti-cancer molecules as important prognostic tools and diagnostic screens for metastatic detection, diagnosis and treatment. ..
- Glioma Immunotherapy Usingengineered T-CellsMichael Jensen; Fiscal Year: 2006..These data will form the basis for designing Phase I/II trials using enhanced T-cell dosing schedules, imaging techniques, and surrogate marker endpoints. ..