| FOR PROFESSIONALS: |
Neuro-OncologyBlood-Brain Barrier Program |
Dr. Edward A. Neuwelt
Education:Dr. Neuwelt attended Northwestern University in Chicago, Illinois from 1965 – 1968 and then received his M.D., magna cum laude, from the University of Colorado School of Medicine in Denver, Colorado in 1972. For his postgraduate Training, Dr. Neuwelt did a surgical internship at the University of Texas Southwestern Medical School in Dallas, Texas, 1972 – 1973, followed by a Neurosurgical Residency at the same institution from 1973 – 1978. During this time, Dr. Neuwelt also completed two neuro-oncology and neurosurgery research fellowships, first at the National Cancer Institute, National Institute of Health (NIH) (1974 – 1976) and then Queen Square Hospital in London, England (1976). While at the NIH, Dr. Neuwelt also completed his military duty as a Clinical Associate (Lt. Commander) in the United States Public Health Service, Neurosurgery and Enzymology Sections in Baltimore, Maryland (July, 1974 - July, 1976). Dr. Neuwelt is certified by the American Board of Neurological Surgery and is a fully trained neuro-oncologist. Faculty Appointments:In Texas, Dr. Neuwelt was Assistant Professor in both Surgery and Biochemistry at the University of Texas Southwestern Medical School. He was also Chief of the Neurosurgery Service at the Dallas Veterans Administration Hospital in Dallas, Texas from 1978 – 1981. Dr. Neuwelt moved his laboratory to Portland Oregon in 1981 where he joined the faculty at the Oregon Health & Science University, both in the Department of Neurology and Biochemistry and Molecular Biology. He was Chief of the Neurosurgery Service at the Veterans Affairs Medical Center in Portland, Oregon 1981 – 1989, and he maintains an affiliation with the Portland VA Neurosurgery Service. Currently Dr. Neuwelt is a Professor of Neurology and an Associate Professor in Neurological Surgery. He is a member of the Neuroscience Graduate Program and Molecular Biology Graduate Program at OHSU, and also regularly teaches the neurology and neurosurgery house staff on topics related to brain tumors. Activities and Organizations:Dr. Neuwelt is the principal investigator of three NIH R01 grants and one VA Merit Review grant. He has been a regular member of the VA Merit Review Study Section on Neurobiology, and an NIH Study Section (NSP-A) that reviews program project and center grants. Dr. Neuwelt is a regular reviewer of neuroscience-related journals, including Neurosurgery, for which he was a member of the editorial board. He initiated and is director of Think First Oregon, a brain and spinal cord injury prevention program. He has eight approved patents, five of which have been licensed to Adherex, Inc. to investigate thiol agent chemoprotection. In collaboration with Dr. James Rosenbaum and Dr. Richard Rosenbaum, Dr. Neuwelt set up and directs a science class for high school students that introduces young people to laboratory research. With regard to the BBB Program, Dr. Neuwelt has overseen the expansion of the program to eight institutions across the US and internationally including Canada and Israel, as well as the annual BBBD Consortium meeting funded by an R13 grant. Publications:Dr. Neuwelt has written or edited several books and book chapters, and has over 200 peer reviewed scientific publications. Selected Clinical Research Publications:The History of BBB Disruption Neuwelt EA, Hill SA, Frenkel EP, Diehl JT, Maravilla KR, Vu LH, Clark WK, Rapoport SI, Barnett PA, Lewis SE, Ehle AL, Beyer CW, Jr. Osmotic blood-brain barrier disruption: Pharmacodynamic studies in dogs and a clinical phase I trial in patients with malignant brain tumors. Cancer Treat Rep 65(suppl):39-43, 1981. Neuwelt EA, Hill SA, Frenkel EP. Osmotic blood-brain barrier modification and combination chemotherapy: Concurrent tumor regression in areas of barrier opening and progression in brain regions distant to barrier opening. Neurosurgery 15:362-366, 1984.
Williams PC, Henner WD, Roman-Goldstein S, Dahlborg SA, Brummett RE, Tableman M, Dana BW, Neuwelt EA. Toxicity and efficacy of carboplatin and etoposide in conjunction with disruption of the blood-brain tumor barrier in the treatment of intracranial neoplasms. Neurosurg 37:17-28, 1995. Dahlborg SA, Petrillo A, Crossen JR, Roman-Goldstein S, Doolittle ND, Fuller KH, Neuwelt EA. The potential for complete and durable response in non-glial primary brain tumors in pediatric patients and young adults with enhanced chemotherapy delivery. Cancer J Sci Am 4:110-124, 1998. Doolittle ND, Miner ME, Hall WA, Siegal T, Hanson EJ, Osztie E, McAllister LD, Bubalo JS, Kraemer DF, Fortin D, Nixon R, Muldoon LL, Neuwelt EA. Safety and efficacy of a multi-center study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of malignant brain tumors. Cancer 88:637-647, 2000. Neuwelt EA, Goldman DL, Dahlborg SA, Crossen J, Ramsey F, Roman-Goldstein S, Braziel R, Dana B. Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: Prolonged survival and preservation of cognitive function. Classic Papers and Current Comments: Highlights of Neurologic Cancer Research – J Clin Oncol 5:360-370, 2000. McAllister LD, Doolittle ND, Guastadisegni PE, Kraemer DF, Lacy CA, Crossen JR, Neuwelt EA. Cognitive outcomes and long-term follow-up after enhanced chemotherapy delivery for primary central nervous system lymphomas. Neurosurg 46:51-61, 2000. Kraemer DF, Fortin D, Doolittle ND, Neuwelt EA. Association of total dose intensity of chemotherapy in primary CNS lymphoma (human non-AIDS) and survival. Neurosurg 48:1033-1041, 2001. Neuwelt EA, Guastadisegni PE, Varallyay P, Doolittle ND. Imaging changes and cognitive outcome in primary CNS lymphoma after enhanced chemotherapy delivery. AJNR Am J Neuroradiol 26:258-65, 2005. Hall WA, Doolittle ND, Daman M, Bruns PK, Muldoon L, Fortin D, Neuwelt EA. Osmotic blood-brain barrier disruption chemotherapy for diffuse pontine gliomas. J Neurooncol [Epub ahead of print, Nov 2005]. Clinical Studies: Antibody Delivery to
the Brain Neuwelt EA, Specht D, Larson S, Krohn K, Hellström K, Hellström I, Dahlborg SA, Barnett P. Increased delivery of tumor-specific monoclonal antibodies to brain after osmotic blood-brain barrier modification in patients with melanoma metastatic to the central nervous system. Neurosurgery 20:885-895, 1987. Neuwelt EA, Barnett PA, Hellström KE, Hellström I, Beaumier P, McCormick CI, Wigel R. Delivery of melanoma-specific immunoglobulin monoclonal antibody and Fab fragments to normal brain utilizing osmotic blood-brain barrier disruption. Cancer Res 48:4725-4729, 1988. Tyson RM, Kraemer DF, Hunt MA, Orbay P, Muldoon LL, Steeg PS, Neuwelt
EA. Chemothrapy with or without trastuzumab, a monoclonal antibody,
and blood-brain barrier disruption for breast cancer brain metastases.
Expert Review Anti-Cancer Therapy 3:97-112, 2006. Clinical Studies: Nanoparticle Delivery and Imaging Neuwelt EA, Várallyay P, Bagó AG, Muldoon LL, Nesbit G, Nixon R. Imaging of iron oxide nanoparticles by MR and light microscopy in patients with malignant brain tumors. Neuropath Applied Neurobiol 30:456-471, 2004. Manninger SP, Muldoon LL, Nesbit G, Murillo T, Jacobs PM, Neuwelt EA. An exploratory study of ferumoxtran-10 nanoparticles as a blood brain barrier imaging agent targeting phagocytic cells in CNS inflammatory lesions. AJNR: Am J Neuroradiol 26:2290-2300, 2005. Hunt MA, Bago AG, Neuwelt EA. Single-dose contrast agent for intraoperative
MR imaging of intrinsic brain tumors by using ferumoxtran-10. AJNR
Am J Neuroradiol 26:1084-1088, 2005. Doolittle ND, Muldoon LL, Brummett RE, Tyson RM, Lacy C, Bubalo JS, Kraemer DF, Heinrich MC, Henry JA, Neuwelt EA. Delayed sodium thiosulfate as an otoprotectant against carboplatin-induced hearing loss in patients with malignant brain tumors. Clin Cancer Res 7:493-500, 2001. Neuwelt EA., Gilmer-Knight K, Lacy C, Nicholson HS, Kraemer DF, Doolittle ND, Hornig G, Muldoon LL. Toxicity Profile of Delayed High Dose Sodium Thiosulfate in Children Treated with Carboplatin in conjunction with Blood-Brain-Barrier Disruption. Pediatric Blood Cancer [Epub ahead of print, Aug 2005]. Knight KR, Kraemer DF, Neuwelt EA. Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development. J Clin Oncol 23:8588-96, 2005.
Neuwelt EA, Abbott JN, Drewes L, Smith QR, Couraud PO, Chiocca EA, Audus KL, Greig NH, Doolittle ND. Special report. Cerebrovascular biology and the various neural barriers: Challenges and future directions. Neurosurg 44:1-6, 1999. Doolittle ND, Anderson CP, Bleyer WA, Cairncross JG, Cloughesy T, Eck SL, Guastadisegni P, Hall WA, Muldoon LL, Patel SJ, Peereboom D, Siegal T, Neuwelt EA. Importance of dose intensity in neuro-oncology clinical trials. Summary report of the sixth annual meeting of the blood-brain barrier disruption consortium. Neuro-Oncol 3:46-54, 2001. Kraemer DF, Fortin D, Neuwelt EA. Chemotherapeutic Dose intensification for treatment of malignant brain tumors: Recent developments and future directions. Current Neurol Neurosci Reports 2:216-224, 2002. Doolittle ND, Abrey LE, Ferrari N, Hall WA, Laws ER, McLendon RE, Muldoon LL, Peereboom D, Reynolds CP, Senter P, Neuwelt EA. Targeted delivery in primary and metastatic brain tumors: enhanced delivery versus neurotoxicity. Clin. Cancer Res 8:1702-1709, 2002. Quencer RM and Neuwelt EA. Advances in the understanding of the blood-brain barrier in neuro-oncology. AJNR Am J Neuroradiol 23:1807-1810, 2002. Neuwelt EA. Mechanisms of disease: the blood-brain barrier. Neurosurg 54:131-142, 2004. Doolittle ND, Abrey LE, Bleyer WA, Brem S, Davis TP, Dore-Duffy P, Drewes LR, Hall WA, Hoffman JM, Korfel A, Martuza R, Muldoon LL, Peereboom D, Peterson DR, Rabkin SD, Smith Q, Stevens GHJ, Neuwelt EA. New frontiers in translational research in neuro-oncology and the blood-brain barrier: report of the tenth annual blood-brain barrier disruption consortium meeting. Clin Cancer Res 11:421-428, 2005. Muldoon LL, Tratnyek P, Jacobs PM, Doolittle ND, Christoforidis GA, Frank J, Lindau M, Lockman PR, Manninger S, Qiang Y, Spence AM, Stupp SI, Zhang M, Neuwelt EA. Imaging and nanomedicine for diagnosis and therapy in the CNS: Report of the eleventh annual blood-brain barrier disruption consortium meeting. AJNR Am J Neuroradiol 27:715-21, 2006. Doolittle ND, Peereboom DM, Christoforidis GA, Hall WA, Brock P, Campbell K, Dickey DT, Muldoon LL, O’Neill BP, Palmieri D, Peterson DR, Pollock B, Soussain C, Smith Q, Tyson RM, Neuwelt EA. Delivery of chemotherapy and antibodies across the blood-brain barrier and the role of chemoprotection, in primary and metastatic brain tumors: report of the eleventh annual blood-brain barrier consortium meeting. J Neuro-Oncol in press, 2006. Selected Preclinical Research Publications:Preclinical Studies: BBBD Delivery to the CNS Neuwelt EA, Pagel MP, Dix R: Delivery of UV-inactivated 35S-herpesvirus across an osmotically modified blood-brain barrier. J Neurosurg 74:475-479, 1991. Neuwelt EA, Barnett PA, Ramsey FL, Hellström I, Hellström KE, McCormick CI. Dexamethasone decreases the delivery of tumor-specific monoclonal antibody to both intracerebral and subcutaneous tumor xenografts. Neurosurg 33:478-484, 1993. Barnett PA, Roman-Goldstein S, Ramsey F, McCormick CI, Sexton G, Szumowski J, Neuwelt EA. Differential permeability and quantitative MR imaging of a human lung carcinoma brain xenograft in the nude rat. Am J Pathol 146:436-449, 1995. Neuwelt EA, Barnett P, McCormick CI, Remsen LG, Kroll RA, Sexton, G. Differential permeability of a human brain tumor xenograft in the nude rat: The impact of tumor size and method of administration on optimizing delivery of biologically diverse agents. Clin Cancer Res, 4:1549-1556, 1998. Neuwelt EA, Barnett PA, Hellström KE & Hellström I, McCormick CI, Ramsey FL. The effect of blood-brain barrier disruption on intact and fragmented monoclonal antibody localization in intracerebral human carcinoma xenografts. J Nucl Med 35:1831-1841, 1994. Nilaver G, Muldoon LL, Kroll RA, Pagel MA, Breakefield XO Davidson
BL, Neuwelt EA. Delivery of herpes virus and adenovirus to nude rat
intracerebral tumors following osmotic blood-brain barrier disruption.
Proc Natl Acad Sci USA 92:9829-9833, 1995. Preclinical Studies: Therapeutic Approaches Remsen LG, Trail PA, Hellström I, Hellström KE, Neuwelt
EA. Enhanced delivery improves the efficacy of a tumor-specific doxorubicin
immunoconjugate in a human brain tumor xenograft model. Neurosurg
46:704-709, 2000. Muldoon LL, Neuwelt EA. BR96-DOX immunoconjugate targeting of chemotherapy in brain tumor models. J Neuro-Oncol Special issue “Targeted Toxins for Glioma Therapy” 65:49-62, 2003. Neuwelt EA, Thrun LA, Walker-Rosenfeld S, Cave AT, Muldoon LL. Effect of antigenic heterogeneity on the efficacy of targeted chemotherapy in brain tumor xenografts. Neurosurg 53:1406-1413, 2003. Staverosky JA, Leslie L. Muldoon, Guo S, Evans AJ, Neuwelt EA, Clinton GM. Herstatin, an autoinhibitor of the egf receptor family, blocks the intracranial growth of glioblastoma. Clin Cancer Res 11:335-340, 2005
Kroll RA, Pagel MA, Muldoon LL, Neuwelt EA. Increasing volume of distribution to brain with interstitial infusion: dose, rather than convection, may be the most important factor. Neurosurgery, 38:746-754, 1996. Muldoon LL, Pagel MA, Kroll RA, Roman-Goldstein S, Jones RS, Neuwelt EA. A physiologic barrier distal to the anatomic blood-brain barrier in a model of transvascular delivery. AJNR Am J Neuroradiol 20:217-222, 1999. Muldoon LL, Varallyay P, Kraemer DF, Kiwic G, Pinkston K, Walker-Rosenfeld SL, Neuwelt EA. Trafficking of superparamagnetic iron oxide particles (Combidex) from brain to lymph nodes in the rat. Neuropathology Applied Neurobiology 30:70-79, 2004. Muldoon LL, Manninger S, Pinkston KE, Neuwelt EA. Imaging, distribution, and toxicity of superparamagnetic iron oxide magnetic resonance nanoparticles in the rat brain and intracerebral tumor. Neurosurgery 57:785-96, 2005.
Muldoon LL, Pagel MA, Kroll RA, Brummett RE, Doolittle ND, Zuhowski EG, Egorin MJ, Neuwelt EA. Delayed administration of sodium thiosulfate in animal models reduces platinum ototoxicity without reduction of antitumor activity. Clin Cancer Res, 6:309-315, 2000. Neuwelt EA, Pagel MA, Hasler BP, Deloughery TG, Muldoon LL. Therapeutic efficacy of aortic administration of N-acetylcysteine as a chemoprotectant against bone marrow toxicity after intracarotid administration of alkylators, with or without glutathione depletion in a rat model. Cancer Res 61:7868-7874, 2001. Dickey DT, Muldoon LL, Kraemer DF, and Neuwelt EA. Protection against cisplatin-induced ototoxicity and nephrotoxicity by N-acetylcysteine in a rat model. Hearing Res 193:25-30, 2004. Neuwelt EA, Pagel MA, Kraemer DF, Peterson DR, Muldoon LL. Bone marrow chemoprotection without compromise of chemotherapy efficacy in a rat brain tumor model. J Pharmacol Exp Therapeut 309:594-599, 2004. Wu YJ, Muldoon LL, Neuwelt EA. The chemoprotective agent N-acetylcysteine blocks cisplatin-induced apoptosis through caspase signaling pathway. J Pharmacol Exp Therapeut 312:424-431, 2005. Dickey DT, Wu YJ, Muldoon LL, Neuwelt EA. Protection against cisplatin-induced
toxicities by N-acetylcysteine and sodium thiosulfate as assessed
at the molecular, cellular, and in vivo levels. J Pharmacol Exp Therapeut
314:1052-8, 2005. |
