Abstract:
:Our laboratory and others have shown alternative splicing of up to ten exons at a discrete extracellular site to be primarily responsible for the generation of CD44 variant (CD44v) isoforms. Based on clear differences in the expression of these CD44v isoforms between normal and malignant tissues, we believe that elucidation of the mechanisms underlying the regulation of CD44 alternative splicing may provide a new gene therapeutic targeting approach based on CD44 pre-mRNA processing in vivo. This strategy incorporates utilization of CD44 alternative splicing control elements into a chimeric enzyme/prodrug therapy (CEPT), a novel modification of the virus-directed enzyme/prodrug therapy (VDEPT) approach for the treatment of brain metastases from tumors of systemic origin. As initial steps towards the development of a gene therapeutic approach based on targeting tumor cell expression of specific CD44v alternatively spliced isoforms, we have: (1) developed a novel in vivo assay system that allows the rapid analyses of potentially therapeutic CD44 alternative splicing minigene constructs; and (2) cloned the E. coli cytosine deaminase (CD) gene and fused its enzymatically active domain to alternatively spliced CD44 exons (CD44/CD). Deamination of cytosine by this CD44/CD chimeric fusion protein is demonstrated in E. coli cell lysates to be equal to that of wild type cytosine deaminase.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Asman DC,Dirks JF,Ge L,Resnick NM,Salvucci LA,Gau JT,Becich MJ,Cooper DL,Dougherty GJdoi
10.1007/BF01052627subject
Has Abstractpub_date
1995-12-01 00:00:00pages
243-50issue
3eissn
0167-594Xissn
1573-7373journal_volume
26pub_type
杂志文章abstract::The objective of this study was to investigate whether activity and protein expression of ornithine decarboxylase (ODC) the metabolism-rate limiting enzyme of the polyamine biosynthesis, which is involved in the regulation of cellular growth and differentiation, reflects the distinct histopathologic characteristics in...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/b:neon.0000013483.50955.2f
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Clinical trials directed at mechanistic target of rapamycin (mTOR) inhibition have yielded disappointing results in glioblastoma (GBM). A major mechanism of resistance involves the activation of a salvage pathway stimulating internal ribosome entry site (IRES)-mediated protein synthesis. PRMT5 activity has...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03274-0
更新日期:2019-10-01 00:00:00
abstract::Embryonal tumors are an aggressive subtype of high-grade, pediatric central nervous system (CNS) tumors often with dismal survival rates. The 5-year survival for highest-risk embryonal tumors may be as low as 10 %. We report feasibility and efficacy from our experience using intravenous (IV) cyclophosphamide concurren...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-012-0969-2
更新日期:2012-11-01 00:00:00
abstract::Since the introduction of CT and MRI as diagnostic aids, it has been possible to obtain direct images of neoplastic meningiosis. After more than ten years experience, the combination of MRI with the administration of a paramagnetic contrast medium is now accepted as the method of choice for the sensitive detection of ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1023/a:1005914321578
更新日期:1998-06-01 00:00:00
abstract::The activation of autocrine loops involving proto-oncogene related receptor tyrosine kinases has led to the analysis of a large number of growth factor systems in human glioma specimens and cell lines. The ErbB-2 system, also called HER-2 or neu, is analogous to the epidermal growth factor receptor system (EGF-R, ErbB...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005837122181
更新日期:1997-12-01 00:00:00
abstract::Approximately half of surgically-treated patients with low-grade-glioma (LGG) suffer recurrence or metastasis. Currently there is no effective drug treatment. While the selective COX-2 inhibitor celecoxib showed anti-neoplastic activity against several malignant tumors, its effects against LGG remain to be elucidated....
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2380-5
更新日期:2017-04-01 00:00:00
abstract::Dysembryoplastic neuroepithelial tumors (DNET) are usually benign lesions that arise in cortical regions and are discovered after new onset of seizure. These lesions have many different imaging characteristics. We report a patient with a presumed low-grade medial temporal lobe lesion that was followed for many years w...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-005-9054-4
更新日期:2006-05-01 00:00:00
abstract::The stable isotope 10B has a peculiarly marked avidity to capture slow neutrons whereupon it disintegrates into a lithium and a helium atom. These give up the 2.4 MeV of disintegration energy which they share within 5 and 9 microns of the 10B atom respectively. This means that the cell closest to the 10B atom bears th...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1023/a:1005752827194
更新日期:1997-05-01 00:00:00
abstract::Malignant gliomas (MG) are very aggressive tumors. In an effort to improve the outcome, the patients receive multi-modal therapies such as surgery, radiation and chemotherapy (temozolomide followed in many cases by bevacizumab). The survivors are affected by multiple learning and memory deficits. Greater deterioration...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2188-8
更新日期:2016-09-01 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::Type 2 diabetes mellitus (DM) and obesity are known risk factors for poor outcomes in patients with systemic malignancies but are not well-studied in the brain tumor population. In this study we asked if type 2 DM and elevated body mass index (BMI) are independent risk factors for poor prognosis in patients with high-...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-011-0676-4
更新日期:2012-01-01 00:00:00
abstract::Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor response to bevacizumab is complex and there is no validated method of monitoring tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging (PW...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2300-0
更新日期:2017-01-01 00:00:00
abstract::Transfection of primary cultures of human cells with origin of replication deficient SV40 DNA has been carried out by others to generate in vitro models of malignant transformation in vivo. The present work describes progressive alterations in karyotype and phenotype in one such transfected (neuroglial) cell line (SVG...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00182082
更新日期:1990-02-01 00:00:00
abstract::Human astrocytomas frequently co-express Fas (APO-1/CD95) and Fas ligand (FasL), yet do not appear to be overly susceptible to suicidal, fratricidal and immune-mediated elimination. This suggests that these gliomas have acquired mechanisms to prevent Fas-mediated apoptosis from occurring. Candidates for such a role in...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1006311231189
更新日期:1999-01-01 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::We describe the case of a young man presenting with an extra-nodal, intramedullary non-Hodgkin's lymphoma of the cervical spinal cord. This is a very uncommon presentation of this neoplasm. The patient was treated with craniospinal radiotherapy, with survival for two and a half years before death from recurrent diseas...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF01059959
更新日期:1995-01-01 00:00:00
abstract::Various subtypes of intracerebral hamartomas, associated with seizure disorders, have long been described. We describe a cerebral hamartoma placed in the left frontal lobe, associated with drug-resistant epilepsy, composed exclusively of mature oligodendroglial cells. The patient was a 27-year-old right-handed male pr...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-010-0253-2
更新日期:2011-01-01 00:00:00
abstract::In this review on current concepts in radiation therapy in the treatment of incompletely resected supratentorial low-grade glioma, a number of important issues are discussed. They include indication for radiation therapy, timing (early vs delayed), dose response issue, impact of modern neuroimaging, 'optimal' treatmen...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1023/a:1013333905202
更新日期:2001-11-01 00:00:00
abstract::Calcification is a rare phenomenon in high grade glioma (HGG). CT scans are sensitive to mineralization but used infrequently for tumor assessment in the MRI era. The presence of calcification can be overlooked on routine MRI. Calcification may reflect chronicity and natural changes in the tumor or its milieu over tim...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1796-z
更新日期:2015-06-01 00:00:00
abstract::Primary brain tumors cumulatively represent the most common solid tumors of childhood and are the leading cause of cancer related death in this age group. Traditionally, molecular findings and histological analyses from biopsies of resected tumor tissue have been used for diagnosis and classification of these diseases...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-014-1432-3
更新日期:2014-06-01 00:00:00
abstract::Malignant glioma (MG), the most common primary brain tumor in adults, is extremely aggressive and uniformly fatal. Several treatment strategies have shown significant preclinical promise in murine models of glioma; however, none have produced meaningful clinical responses in human patients. We hypothesize that introdu...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2753-4
更新日期:2018-05-01 00:00:00
abstract::Boron neutron capture therapy (BNCT) is an experimental form of radiation therapy for malignant brain tumors and peripheral melanoma. The micro-distribution of the boron compound is critical to determine the radiation effects for both tumors and normal tissue. In the current dose calculation of BNCT, normal brain tiss...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-007-9494-0
更新日期:2008-03-01 00:00:00
abstract:QUESTION:Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings? Target population These recommendations apply to adults with a newly diagnosed single b...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-009-0061-8
更新日期:2010-01-01 00:00:00
abstract::The p21WAF1/Cip1 (p21) protein, a negative regulator of G1 checkpoint control, was overexpressed in the majority of human gliomas. To investigate whether p21 expression in brain metastases from various systemic origins is similar to that in gliomas and whether p21 expression is regulated differently in brain metastase...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005972808311
更新日期:1998-05-01 00:00:00
abstract::Long non-coding RNAs (lncRNAs) are important modulators of various cellular and molecular events, including cancer-associated pathways. The Anti-differentiation ncRNA (ANCR) is a key regulator of keratinocyte differentiation, where its expression is necessary to maintain epidermal progenitor's cells. Herein, we invest...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2809-5
更新日期:2018-06-01 00:00:00
abstract::Glioblastoma Multiforme frequently metastasises from their original location by for example infiltration along white matter tracts [1]. GBM metastasis outside the central nervous system is distinctly rare though there are previous reports of spread to various organs [2-5]. We add an unusual case of a patient with aggr...
journal_title:Journal of neuro-oncology
pub_type: 信件
doi:10.1007/s11060-005-1480-9
更新日期:2005-09-01 00:00:00
abstract:PURPOSE:Prediction of clinical outcomes in patients with primary central nervous system lymphoma (PCNSL) is important for optimization of treatment planning. Quantitative imaging biomarkers for PCNSL have not yet been established. This study evaluated the prognostic value of pretreatment dynamic contrast-enhanced MRI a...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2960-z
更新日期:2018-11-01 00:00:00
abstract::The diagnosis of brain metastases is associated with a poor prognosis reflecting uncontrolled primary disease that has spread to the relative sanctuary of the central nervous system. 20 % of brain metastases occur in the posterior fossa and are associated with significant morbidity. The risk of acute hydrocephalus and...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2254-2
更新日期:2016-12-01 00:00:00
abstract::ERCC1 and ERCC2 have been known to belong to the nucleotide excision repair (NER) pathway and are essential to the repair of cisplatin DNA adducts. In the present study, we have examined the potential correlation of ERCC1, ERCC2 mRNA expression and single nucleotide polymorphism (SNP) to chemotherapy drug cytotoxicity...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-006-9290-2
更新日期:2007-05-01 00:00:00
abstract::Pediatric glial tumors differ from adult gliomas in several ways that are of major therapeutic importance. First, the value of extensive tumor resection, which is controversial for malignant intrinsic brain tumors in adults, has been confirmed for a variety of childhood brain tumors, such as supratentorial high-grade ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1023/a:1006107227856
更新日期:1999-05-01 00:00:00