Abstract:
:Developing and conducting gene therapy clinical trials poses unique challenges which must be addressed to satisfy regulatory requirements and, most importantly, to protect human subjects. Experimental products used for gene transfer studies, such as viral vectors, are often complex and cannot be sterilized or completely characterized to the extent of a typical pharmaceutical. Thus, quality and characterization must be built into the production process. Extensive preclinical studies must be performed to determine the feasibility of the approach, the safety of the product, and the appropriate dose range to evaluate in humans. Once a clinical trial is initiated, subjects must be followed carefully for short- and long-term toxicity especially since preclinical studies may not adequately predict the toxicity profile of these novel, complicated products. Results of early phase studies in gene therapy have often sent the investigators back to the laboratory to improve the delivery vector or identify a more potent or less toxic gene. This circular developmental process is expected for the early stages of a new technology such as gene therapy. Although these hurdles appear extensive, they can be overcome, as evidenced by the initiation of more than 500 clinical gene therapy trials in the United States to date, and are imperative for the maintenance of high-quality studies and public trust. This article describes the step-by-step process for developing a gene therapy trial incorporating specific examples relevant to neuro-oncology.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Aguilar LK,Aguilar-Cordova Edoi
10.1023/b:neon.0000003659.04633.6esubject
Has Abstractpub_date
2003-12-01 00:00:00pages
307-15issue
3eissn
0167-594Xissn
1573-7373journal_volume
65pub_type
杂志文章,评审abstract:OBJECTIVE:Atypical and malignant meningiomas are at high risk for local failure. The role of radiation therapy (RT) and dose levels required to improve tumor control are poorly defined. This study reviews our experience with RT. MATERIAL AND METHODS:Thirty-one patients underwent fractionated RT for atypical (AM, 15 pa...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1006434124794
更新日期:2000-06-01 00:00:00
abstract::There is a need for better predictors for short survival in patients with brain metastases undergoing open surgery. The graded prognostic assessment (GPA) has recently been developed to predict survival in patients with brain metastases. We explored the prognostic capabilities of GPA in a consecutive neurosurgical pop...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-011-0623-4
更新日期:2011-12-01 00:00:00
abstract:PURPOSE:Glioblastoma multiforme (GBM) is a common and aggressive malignancy associated with poor prognosis. Characteristics and treatment of long-term survivors are of particular interest in efforts to improve outcomes. Therefore, the objective of this study was to examine trends and prognostic factors for 3-year survi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-020-03469-w
更新日期:2020-05-01 00:00:00
abstract::We report a case of radiation necrosis occurring 47 years after resection and radiotherapy for a juvenile pilocystic cerebellar astrocytoma, the longest yet reported. The patient presented with progressive lower cranial nerve dysfunction, and eventually died from cardiopulmonary arrest secondary to aspiration. The pre...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/BF01054272
更新日期:1993-07-01 00:00:00
abstract::Gliomas, the most common malignant primary brain tumors, are universally fatal once they progress from low-grade into high-grade neoplasms. In recent years, we have accumulated unprecedented data about the genetic and epigenetic abnormalities in gliomas; yet, our appreciation of how these deadly tumors arise is still ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-014-1499-x
更新日期:2014-09-01 00:00:00
abstract::We report a case of high risk medulloblastoma with leptomeningeal intracranial and spinal metastasis in a 10-year-old girl treated successfully with conventional prolonged chemotherapy without radiotherapy. This is a particular case of medulloblastoma that at onset did not receive standard therapy for medulloblastoma ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1006365511379
更新日期:1999-01-01 00:00:00
abstract:PURPOSE:Stereotactic radiosurgery is an established treatment option for sporadic meningiomas, though limited data exists for radiation-induced lesions. METHODS:Patients treated with cobalt-60 radiosurgery between October 2005 and December 2018 in an institutional registry were reviewed. Single fraction treatments wer...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-020-03515-7
更新日期:2020-06-01 00:00:00
abstract::Angiogenesis, the formation of blood vessels from a pre-existing vasculature, is a process whereby capillary sprouts are formed in response to externally supplied chemical stimuli. The sprouts then grow and develop, driven initially by endothelial cell migration, and organize themselves into a branched, connected netw...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1023/a:1006446020377
更新日期:2000-10-01 00:00:00
abstract::Targeting tumor angiogenesis is a potential therapeutic strategy for glioblastoma because of its high vascularization. Tivozanib is an oral pan-VEGF receptor tyrosine kinase inhibitor that hits a central pathway in glioblastoma angiogenesis. We conducted a phase II study to test the effectiveness of tivozanib in patie...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2332-5
更新日期:2017-02-01 00:00:00
abstract::Primary malignant brain and other central nervous system tumors (BT) are a rare cancer that causes morbidity and mortality disproportionate to their incidence. This study presents the most up-to-date mortality data for malignant BT in the United States (US) by histology groupings, age, race, and sex. Mortality rates f...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2449-1
更新日期:2017-06-01 00:00:00
abstract::There is considerable interest in the role of the TRK family of neurotrophin receptors in regulating the survival, growth and differentiation of normal and neoplastic nerve cells. Indeed, there is increasing evidence that TRK genes play an important role in the biology and clinical behavior of neuroblastomas, tumors o...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005729329526
更新日期:1997-01-01 00:00:00
abstract::Neurological complications may occur in the course of Waldenström's macroglobulinemia (Wm). These complications affect both the central and peripheral nervous system. Pathogenesis is debated and several mechanisms have been suggested. Direct malignant lymphoid infiltration (MLI) is very rare and has only been reported...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1023393532546
更新日期:2003-05-01 00:00:00
abstract::Identification of patients suffering from elevated psychosocial distress, the sources of the distress, and the necessary treatment of the distress can be rather difficult within the neurosurgical setting (e.g., lack of time, cognitive or aphasic disorders of the patients). The distress thermometer (DT) is a single-ite...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-010-0501-5
更新日期:2011-08-01 00:00:00
abstract::This review identifies the current literature on the use of bevacizumab for cerebral radiation necrosis in patients with high-grade gliomas, summarizes the clinical course and complications following bevacizumab, and discusses the relative costs and benefits of this therapeutic option. A Medline search was conducted o...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-013-1233-0
更新日期:2013-12-01 00:00:00
abstract::Fibroblast growth factor-2 (FGF-2) is involved as an autocrine growth factor in the autonomous proliferation of glioma cells. To develop a new strategy for treating patients with glioma, we studied the effect on human glioma cells of a 16-mer oligopeptide with conformational similarity to the putative receptor-binding...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1023908307863
更新日期:2003-06-01 00:00:00
abstract::The endothelins (ETs) are a family of three peptides named ET-1, ET-2 and ET-3 that have been initially isolated as potent vasoactive peptides; ETs are synthesized as precursor proteins (preproETs) and are activated by proteolytic cleavage. ETs exert their biological effects through the activation of two receptors sub...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-005-9111-z
更新日期:2006-08-01 00:00:00
abstract::Proliferative activities were determined in 72 human brain tumors, including 20 metastatic carcinomas, 41 gliomas, 8 meningiomas and 3 hematological tumors. Immunocytochemical techniques included labeling with monoclonal antibody (mAb) to bromodeoxyuridine (BrdU) which identifies S phase cells after previous in vitro ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00151242
更新日期:1991-02-01 00:00:00
abstract:PURPOSE:Comparison of the influence of two different brain tumors (C6 and CNS1 glioma) on methotrexate (MTX) disposition in plasma, brain, and tumor tissue extracellular fluid (ECF). METHODS:Serial collection of plasma samples and brain ECF dialysates after i.v. bolus administration of MTX (50 mg kg(-1)) for 4 h. Quan...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/b:neon.0000021820.12444.4c
更新日期:2004-03-01 00:00:00
abstract::Assessing central nervous system (CNS) involvement in patients with lymphoma or carcinoma is important in determining therapy and prognosis. Progranulin (PGRN) is a secreted glycosylated protein with roles in cancer growth and survival; it is highly expressed in aggressive cancer cell lines and specimens from many can...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2742-z
更新日期:2018-05-01 00:00:00
abstract::The aim of the present study was to evaluate the spectrum of late effects in a large cohort of pediatric patients with low-grade gliomas (WHO grade I and II) during an observation period of 20 years. Eighty-seven patients with low-grade gliomas grouped according to tumor location (cerebellum: n=28; cerebral hemisphere...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-005-9091-z
更新日期:2006-06-01 00:00:00
abstract::In meningiomas, transformed meningeal cells can share morphological aspects (in hemangiopericytic meningioma) and antigenic properties (i.e.: HLA-DR antigens expression) with elements of the monocyte/macrophage lineage. In this report, we describe a case of a highly vascular meningioma where numerous tumor cells, stud...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00172943
更新日期:1992-05-01 00:00:00
abstract::High grade astrocytomas remain incurable even though these tumors often appear localized on modern imaging studies, rarely metastasize to systemic sites, and can be aggressively treated with surgery and radiation therapy. Recent data suggest that the dissemination of astrocytoma cells along white matter tracts to dist...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005761031077
更新日期:1997-05-01 00:00:00
abstract::The new anticancer agent Taxol appears to potentiate the effects of radiation on brain tumor cell lines in vitro and was recently evaluated by our group as a radiosensitizer in a phase I study for primary brain tumors. In that study, we administered Taxol as a three-hour IV infusion repeated every week for six weeks a...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005710710418
更新日期:1998-09-01 00:00:00
abstract::The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity levels, prevalence and...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1821-2
更新日期:2015-09-01 00:00:00
abstract::The aim of the present study is to evaluate the impact of extent of resection at initial and repeat craniotomy on overall survival of patients with recurrent glioblastoma. The authors retrospectively reviewed the records of all adults patients who underwent repeat resection of recurrent glioblastoma following radiatio...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2330-7
更新日期:2017-02-01 00:00:00
abstract::This paper presents a study of the effects of scanning parameters variability when assessing glioma sizes on MRI. A database of lesions of various shapes and sizes, segmented on 3D-SPGR MRI images, was acquired on 65 patients with low-grade glioma. Simulations of large slice thickness and patient's head rotation were ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-013-1051-4
更新日期:2013-04-01 00:00:00
abstract::The time to tumor progression (TTP), time to death (TTD) and complications were studied prospectively in a cohort of patients treated by surgery and adjuvant radio- and intensified PCV chemotherapy for astrocytomas (AIII), oligodendrogliomas (OIII) and oligoastrocytomas (OAIII) WHO grade III. The treatment was carried...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1019987116596
更新日期:2002-09-01 00:00:00
abstract::Gemistocytic astrocytoma still continues to be enigmatic; both in terms of definition and prognostic implications. The major issue of contention has been the clinical relevance of this pathological entity. The currently accepted definition of gemistocytic astrocytoma requires 20% or more gemistocytes, and considers th...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-005-4897-2
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Anaplastic lymphoma kinase (ALK) is expressed in ~ 60% of glioblastomas and conveys tumorigenic functions. Therefore, ALK inhibitory strategies with alectinib are conceivable for patients with glioblastoma. The aims of this preclinical study were to investigate efficacy as well as to understand and potential...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03348-z
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Paclitaxel-induced peripheral neuropathy (PN) may be severe and dose-limiting at initial doses > or = 275 mg/M2, but its neurotoxicity at doses < or = 250 mg/M2 has been incompletely characterized. The purposes of this study were to characterize and quantify paclitaxel-induced PN and to determine the utility...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1023/a:1005805907311
更新日期:1997-10-01 00:00:00