Abstract:
:The aim of this study is to investigate the anti-cancer effect of the bispecific diphtheria toxin (DT) based immunotoxin DTATEGF, which targets both the epidermal growth factor (EGF) receptor (EGFR) and the urokinase-type plasminogen activator (uPA) receptor (uPAR) in vitro and in vivo when delivered by convection-enhanced delivery (CED) via an osmotic minipump in a human metastatic non-small cell lung cancer (NSCLC) brain tumor mouse xenograft model. The effects of the bispecific immunotoxin DTATEGF, and monospecific DTAT, DTEGF and control DT at various concentrations were tested for their ability to inhibit the proliferation of human metastatic NSCLC PC9-BrM3 cells in vitro by MTT assay. A xenograft model of human metastatic NSCLC intracranial model was established in nude mice using the human NSCLC PC9-BrM3 cell line genetically marked with a firefly luciferase reporter gene. One microgram of DTATEGF in the treatment group or control DT in the control group was delivered intracranially by CED via an osmotic minipump. The bioluminescent imaging (BLI) was performed at day 7, 14, 1 month, 2 months, and 3 months. Kaplan-Meier survival curves for the two groups were generated. The brain tissue samples were stained by hematoxylin and eosin for histopathological assessment. In vitro, DTATEGF could selectively kill PC9-BrM3 cells and showed an IC(50) less than 0.001 nM, representing a more than 100- to 1000-fold increase in activity as compared to monospecific DTAT and DTEGF. In vivo, mice with tumors were treated intracranially with drug via CED where the results showed the treatment was successful in providing a survival benefit with the median survival of mice treated with DTATEGF being significantly prolonged relative to controls (87 vs. 63 days, P = 0.006). The results of these experiments indicate that DTATEGF kills the NSCLC PC9-BrM3 cell line in vitro, and when it is delivered via CED intracranially, it is highly efficacious against metastatic NSCLC brain tumors. DTATEGF is a safe and effective drug where further preclinical and clinical development is warranted for the management of metastatic brain tumors.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Huang J,Li YM,Massague J,Sicheneder A,Vallera DA,Hall WAdoi
10.1007/s11060-012-0904-6subject
Has Abstractpub_date
2012-09-01 00:00:00pages
229-38issue
2eissn
0167-594Xissn
1573-7373journal_volume
109pub_type
杂志文章abstract:PROPOSE:To explore the value of unmeasurable enhancement pattern of residual cavity in predicting survival at early stage after gross-total resection in high-grade glioma (HGG) patients. METHODS:This retrospective study enrolled consecutive 51 HGG patients with unmeasurable enhancement who underwent gross-total resect...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2961-y
更新日期:2018-11-01 00:00:00
abstract::NF1, NF2, and Schwannomatosis are incurable tumor suppressor syndromes associated with poor quality of life. The aim of this study was to determine the feasibility, acceptability, and preliminary efficacy of an NF adapted, 8-week group mind body skills based intervention, the relaxation response resiliency program (3R...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-014-1522-2
更新日期:2014-10-01 00:00:00
abstract::The role of repeat resection in the multimodal treatment of gliomas is unclear. Repeat surgery theoretically carries a higher risk of inducing neurological deficits, which might even out any advantage of cytoreduction. We sought to determine whether the occurrence of perioperative infarction is higher for repeat surge...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-011-0784-1
更新日期:2012-05-01 00:00:00
abstract::Levels of rhodamine 123 (Rh-123), a new antineoplastic drug, were measured using high performance liquid chromatography in normal brain, malignant glioma and brain adjacent to tumor after a single intravenous injection of drug into rats with intracerebral tumors. Consistently higher levels of Rh-123 were seen in tumor...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00177430
更新日期:1988-12-01 00:00:00
abstract::Five quantitative histologic factors, differing linear combinations of 26 reliably recognized histologic features, account for much of the histologic variance in 1068 children with infratentorial neuroglial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the Spongy,...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1023/a:1005984531474
更新日期:1998-08-01 00:00:00
abstract::Elevated neutrophil-lymphocyte ratio (NLR) may predict worse outcomes in cancer, including glioblastoma (GBM). This study assessed whether change in NLR during focal radiotherapy and concomitant temozolomide (RT-TMZ) provides further prognostic information. This was a retrospective review of patients treated with RT-T...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2395-y
更新日期:2017-05-01 00:00:00
abstract::In the context of bevacizumab therapy for the treatment of progressive malignant gliomas, it is currently unclear how different magnetic resonance imaging (MRI) sequences correlate with each other over time. The objective of this study was to determine if a reliable and predictable relationship over time exists betwee...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-010-0397-0
更新日期:2011-06-01 00:00:00
abstract:PURPOSE:Diffuse pontine tumors are highly lethal, and there are few long-term survivors with the standard treatment of external beam irradiation. We investigated the effectiveness of high-dose thiotepa and etoposide-based chemotherapy regimens with autologous bone marrow rescue (ABMR) in children with pontine tumors. ...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1023/a:1005874508975
更新日期:1998-03-01 00:00:00
abstract:BACKGROUND:The diagnosis of sarcomatous transformation of plexiform neurofibromas in Neurofibromatosis-1 (NF 1) is a clinical and radiological challenge. Considerable overlap exists in the clinical and the radiological characteristics between the benign enlarging neurofibromas and their counterparts undergoing malignan...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-006-9161-x
更新日期:2006-10-01 00:00:00
abstract::In 2007 the WHO Classification of Tumours of the Central Nervous System introduced the entity "glioblastoma with oligodendroglioma component" (GBM/OLIGO). This entity accounts for approximately one in every ten new glioblastomas (GBM). In practice, those mixed gliomas with necrosis which were previously diagnosed as a...
journal_title:Journal of neuro-oncology
pub_type: 评论,杂志文章
doi:10.1007/s11060-010-0523-z
更新日期:2011-09-01 00:00:00
abstract::We have expressed the tumor suppressor p16 under the control of a tetracycline-sensitive promoter in two human glioblastoma cell lines which do not contain endogenous p16. Ectopic p16 expression led to a stable but reversible G1 phase cell cycle arrest, reduced the growth of both cell lines in cell culture, and almost...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1020226130478
更新日期:2002-10-01 00:00:00
abstract::Patients with metastatic well-differentiated thyroid cancer have a generally favorable long-term outcome although multi-organ involvement is a known marker of poor prognosis. Brain metastases are rare, occurring in less than 1% of patients with thyroid cancer. Few patients have been managed with stereotactic radiosurg...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1007/s11060-010-0175-z
更新日期:2010-06-01 00:00:00
abstract::Although their neurocognitive performance is one of the major concerns of patients with high-grade gliomas (HGG) and although neurocognitive deficits have been described to be associated with negative outcome, neurocognitive rehabilitation is usually not integrated into the routine care of patients with malignant glio...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1007/s11060-009-0006-2
更新日期:2010-03-01 00:00:00
abstract::The records of 14 patients with a tumour in the pineal or supra-sellar region seen at The Norwegian Radium Hospital, Oslo between 1973-1980 have been studied retrospectively. The problems with a widely accepted classification are discussed, as well as the choice of treatment (surgery versus radiation) and the indicati...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF02157997
更新日期:1986-01-01 00:00:00
abstract::Recent developments in the treatment of hematological malignancies, especially with the advent of proteasome inhibitors and immunomodulatory drugs in plasma cell dyscrasias, call for an increased collaboration between hematologists and neurologists. This collaboration involves differentiating chemotherapy-induced peri...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-014-1632-x
更新日期:2015-01-01 00:00:00
abstract::The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide derived from human immunodeficiency virus-1. It has been used to facilitate macromolecule delivery to various cell types. This cationic peptide is capable of crossing the blood-brain barrier and therefore might be useful for enhancing th...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2429-5
更新日期:2017-05-01 00:00:00
abstract::Hypoxia-inducible factor (HIF)-1α and HIF-2α expression were investigated immunohistochemically as determinants of prognosis in 42 cases of astrocytic tumors associated with necrosis grade on magnetic resonance (MR) imaging. Expression of HIF-1α was determined immunohistologically. The degree of necrosis on MR images ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-010-0292-8
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive lymphoreticular proliferation, which usually involves the lungs, but may also involve the central nervous system (CNS). Unique involvement of the CNS has been reported rarely. We report our experience with LYG confined to the brain and...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-009-9834-3
更新日期:2009-09-01 00:00:00
abstract:PURPOSE:We evaluated the outcomes after stereotactic radiosurgery (SRS) for patients who developed new or progressive brain disease regardless of whether they had no prior radiation, PCI, or WBRT. METHODS:We retrospectively identified 90 SCLC patients who had SRS between 1991 and 2018. Thirty-one patients had no evide...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03224-w
更新日期:2019-08-01 00:00:00
abstract::Fractionated external beam radiotherapy is an important component of standard treatment for high grade glioma. Due to resource constraints, patients may experience delays in receiving treatment. The purpose of this study was to evaluate the effect of radiotherapy waiting time on survival in patients with high grade gl...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-007-9426-z
更新日期:2007-12-01 00:00:00
abstract:PURPOSE:This study explored the superiority of temozolomide (TMZ) + interferonβ (IFNβ) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. EXPERIMENTAL DESIGN:Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentori...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s11060-018-2831-7
更新日期:2018-07-01 00:00:00
abstract::Infiltrative astrocytic neoplasms are by far the most common malignant brain tumors in adults. Clinically, they are highly problematic due to their widely invasive nature which makes a complete resection almost impossible. Biologic progression of these tumors is inevitable and adjuvant therapies are only moderately ef...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-004-2752-5
更新日期:2004-11-01 00:00:00
abstract::To identify molecular therapeutic targets for glioma, we performed gene expression profiling by using a complementary DNA (cDNA) microarray method and identified the urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180) as a gene expressed highly in glioma tissue compared with the normal brain t...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-010-0398-z
更新日期:2011-06-01 00:00:00
abstract::TERT promoter (TERTp) mutation is the most common mutation in glioblastomas. It creates a putative binding site for Ets/TCF transcription factors, enhancing telomerase expression and activity, whereas the rs2853669 variant disrupts another Ets/TCF binding. We explore here the interaction between these two alterations,...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1999-3
更新日期:2016-02-01 00:00:00
abstract::Ependymomas (EPN) show site specific genetic alterations and a recent DNA methylation profiling study identified nine molecular subgroups. C11orf95-RELA and YAP1 fusions characterise the RELA and YAP1 molecular subgroups, respectively, of supratentorial (ST)-EPNs. Current guidelines recommend molecular subgrouping ove...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2767-y
更新日期:2018-05-01 00:00:00
abstract::The human glioma cell lines, U87 and T98G, were evaluated for their ability to survive and form colonies in an acidic environment of pH(ext) 6.0. In contrast to U87, which showed an 80-90% survival rate, only 40% of T98G cells survived 6 days at pH(ext) 6.0 and lost their colony forming ability when returned to a norm...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9591-8
更新日期:2008-08-01 00:00:00
abstract::Malignancy involving the skull base remains a formidable management challenge. Advances and refinements in diagnostic imaging, instrumentation, microvascular reconstruction, and an improved overall appreciation of the anatomy of the skullbase have extended the boundaries of tumor resectability and in some cases, obvia...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1023/b:neon.0000041882.41369.9b
更新日期:2004-08-01 00:00:00
abstract::Aberrant expression of stem cell-related genes in tumors may confer more primitive and aggressive traits affecting clinical outcome. Here, we investigated expression and prognostic value of the neural stem cell marker CD133, as well as of the pluripotency genes LIN28 and OCT4 in 37 samples of pediatric medulloblastoma...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-011-0647-9
更新日期:2012-01-01 00:00:00
abstract::Glioblastoma (GBM) is the most malignant primary brain tumor and contains tumorigenic cancer stem cells (CSCs), which support the progression of tumor growth. The selection of CSCs and facilitation of the brain tumor niches may assist the development of novel therapeutics for GBM. Herein, hydrogel materials composed o...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2763-2
更新日期:2018-05-01 00:00:00
abstract::Thirty-five adult recurrent GBM patients, divided randomly in two groups of 19 and 16 cases, had been treated with two regimens of chemotherapy: a) 'eight-drugs-in-one-day'; b) procarbazine + CCNU + vincristine (PCV) respectively. Chemotherapy was planned at the tumour relapse and delivered as long as tolerated withou...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00172666
更新日期:1992-02-01 00:00:00