Abstract:
:Thymidine analogs (TAs) are synthetic nucleosides that incorporate into newly synthesized DNA. Halogenated pyrimidines (HPs), such as bromodeoxyuridine (BrdU), are a class of TAs that can be detected with antibodies and are commonly used for birthdating individual cells and for assessing the proliferative index of cell populations. It is well established that HPs can act as radiosensitizers when incorporated into DNA chains, but they are generally believed not to impair normal cell function in the absence of secondary stressors. However, we and others have shown that HP incorporation leads to a sustained suppression of cell cycle progression in mammalian cells, resulting in cellular senescence in somatic cells. In addition, we have shown that HP incorporation results in delayed tumor progression in a syngeneic rat model of glioma. Here we examine ethynyldeoxyuridine (EdU), a newly developed and alkylated TA, for its anti-cancer activity, both in vitro and in vivo. We show that EdU, like HPs, leads to a severe reduction in the proliferation rate of normal and transformed cells in vitro. Unlike HPs, however, EdU incorporation also causes DNA damage resulting in the death of a substantial subset of treated cells. When administered over an extended time as a monotherapy to mice bearing subcutaneous xenografts of human glioblastoma multiforme tumors, EdU significantly reduces tumor volume and increases survival without apparent significant toxicity. These results, combined with the fact that EdU readily crosses the blood-brain barrier, support the continued investigation of EdU as a potential therapy for malignant brain tumors.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Ross HH,Rahman M,Levkoff LH,Millette S,Martin-Carreras T,Dunbar EM,Reynolds BA,Laywell EDdoi
10.1007/s11060-011-0621-6subject
Has Abstractpub_date
2011-12-01 00:00:00pages
485-98issue
3eissn
0167-594Xissn
1573-7373journal_volume
105pub_type
杂志文章abstract::Extraskeletal myxoid chondrosarcoma is a rare tumor with less than 100 cases reported in the literature. The prevalence of anti-Hu positive myxoid chondrosarcoma-associated paraneoplastic subacute cerebellar degeneration is exceedingly rare. We present a report of a patient with confirmed myxoid chondrosarcoma-associa...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-010-0216-7
更新日期:2011-01-01 00:00:00
abstract::There is increasing regulatory pressure for cost containment in neuro-oncology, and rationalization of the observed regional disparities. We investigated the presence of such disparities in New York State and examined the impact of risk adjustment on the magnitude of this variation. We performed a cohort study involvi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2122-0
更新日期:2016-06-01 00:00:00
abstract:PURPOSE:Molecular data has become an essential part of the updated World Health Organization (WHO) grading of central nervous system tumors. However, stereotactic needle biopsies provide only small volume specimens and limit the extent of histologic and molecular testing that can be performed. We assessed the use of a ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-03014-w
更新日期:2019-01-01 00:00:00
abstract::This adjunct to a prospective phase II blinded study of 48 patients with recurrent malignant glioma evaluated the predictive reliability of an extreme drug resistance (EDR) to identify clinical resistance to irinotecan (CPT-11), using fresh tumor biopsies obtained from recurrent patients immediately prior to their fir...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1023/b:neon.0000014549.77646.f6
更新日期:2004-02-01 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::Little is known on the natural history, recurrence patterns, neurocognitive outcomes and prognostic factors associated with survival in long-term survivors (≥10 years) from brain metastasis (BM). In this study, the records of 1953 patients who underwent treatment for BM with a potential for ≥10 years of follow-up were...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2208-8
更新日期:2016-09-01 00:00:00
abstract::Medulloblastoma is a rare malignancy in adults, accounting for approximately 1% of all primary brain tumors. Extraneural metastases have been reported in 10-30% of cases and most commonly involve bone; rarely lymph nodes, visceral organs and bone marrow may be involved with disease. We report here our experience with ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-005-9087-8
更新日期:2006-06-01 00:00:00
abstract::Glioblastomas are aggressive brain tumors that frequently recur in the subventricular zone (SVZ) despite maximal treatment. The purpose of this study was to evaluate imaging patterns of subventricular progression and impact of recurrent subventricular tumor involvement and radiation dose to patient outcome. Retrospect...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2822-8
更新日期:2018-07-01 00:00:00
abstract:PURPOSE:Recent advances in targeted therapy have prolonged overall survival (OS) for patients with lung cancer. The impact of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) on brain metastases (BM) treated with stereotactic radiosurgery (SRS) has not, however, been fully elucidated. We investiga...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03282-0
更新日期:2019-10-01 00:00:00
abstract::The relation between hospital volume and outcomes for patients with glioblastoma is unknown. We undertook this study to determine the effect of hospital volume on treatment received and its effect on survival in patients with glioblastoma. We included patients from the National Cancer Database diagnosed with a gliobla...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2598-2
更新日期:2017-12-01 00:00:00
abstract::Central neurocytomas are uncommon intraventricular neoplasms whose optimal management remains controversial due to their rarity. We assessed outcomes for a historical cohort of neurocytoma patients and evaluated effects of tumor atypia, size, resection extent, and adjuvant radiotherapy. Progression-free survival (PFS)...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1959-y
更新日期:2016-01-01 00:00:00
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::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::The labeling index (LI) of 216 cases of human brain tumors was determined by the immunohistochemical technique with monoclonal antibody to bromodeoxyuridine (BrdU). The proliferative potential of 110 cases was estimated using the intra-operative intravenous infusion of BrdU at a dose of 200 mg/sq m. In another 106 cas...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1007/BF01059949
更新日期:1995-01-01 00:00:00
abstract::Glucocorticoids, such as betamethasone, are often used to prevent possible acute reactions during radiation therapy of intracranial tumors (for example gliomas). The effect of the glucocorticoids is probably due to vascular changes decreasing the development of edemas. The radiosensitivity of two studied cell-lines of...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00182086
更新日期:1990-02-01 00:00:00
abstract::Although bevacizumab has not proven effective in adults with newly diagnosed high-grade gliomas (HGG), feasibility in newly diagnosed children with diffuse intrinsic pontine gliomas (DIPG) or HGG has not been reported in a prospective study. In a safety and feasibility study, children and young adults with newly diagn...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-2008-6
更新日期:2016-03-01 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::Latino Americans are a rapidly growing ethnic group in the United States but studies of glioblastoma in this population are limited. We have evaluated characteristics of 21,184 glioblastoma patients from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. This SEER data fro...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1007/s11060-017-2377-0
更新日期:2017-04-01 00:00:00
abstract::Primary germinomas in the spinal cord are very rare with only 15 cases published previously. In this case a 22-year-old woman with urinary incontinence, lumbago, and bilateral leg pain and weakness was found to have a solid tumor in the conus medullaris between the L1 and L2 vertebral bodies. Serum HCG was elevated wi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-005-3092-9
更新日期:2006-01-01 00:00:00
abstract::Treatment options and prognosis remains poor for patients with recurrent glioblastoma multiforme. These tumors are highly vascularised and over express angiogenic factors such as vascular endothelial growth factor and may potentially be responsive to antiangiogenic therapies. We present the results of a phase II trial...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1023/a:1012554328801
更新日期:2001-08-01 00:00:00
abstract::Children with pontine glioma usually present classically with ataxia, motor deficits and cranial nerve palsies. The pons has generally not been regarded as a structure that mediates complex affective behaviour. However, we report nine children who either at the time of presentation or progression demonstrated marked b...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-005-9034-8
更新日期:2006-05-01 00:00:00
abstract::In this retrospective, IRB-exempt study, we analyzed data from 68 patients diagnosed with glioblastoma (GBM) in two institutions and investigated the relationship between tumor shape, quantified using algorithmic analysis of magnetic resonance images, and survival. Each patient's Fluid Attenuated Inversion Recovery (F...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1007/s11060-016-2359-7
更新日期:2017-03-01 00:00:00
abstract::Immune checkpoint inhibitors have demonstrated remarkable benefits in cancer patients. However, concern regarding toxicity in the setting of stereotactic radiosurgery (SRS) is often raised. In this study, we characterize radiation necrosis (RN) following immunotherapy and SRS. Melanoma patients treated with SRS and an...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2470-4
更新日期:2017-07-01 00:00:00
abstract::Neural cell adhesion molecule (NCAM) is a cell surface glycoprotein whose expression may be important in metastatic or local growth of neoplasms. Expression of NCAM in human pituitary adenomas was assessed on snap-frozen and Bouin's and/or formalin-fixed, paraffin-embedded archival tissue using a sensitive alkaline ph...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF01053153
更新日期:1995-01-01 00:00:00
abstract:INTRODUCTION:Brain tumors make up over a quarter of pediatric malignancies. Depending on the age of presentation and treatment, pediatric brain tumor survivors experience varying degrees of treatment induced morbidity and sequelae. Epigenetic mechanisms play a critical role in silencing of tumor suppressor genes and ac...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-020-03535-3
更新日期:2020-10-01 00:00:00
abstract::Leptomeningeal spread of childhood primary central nervous system (CNS) neoplasms, also known as leptomeningeal disease (LMD), significantly affects prognosis and treatment. Lumbar cerebrospinal fluid (CSF) cytology and spinal magnetic resonance imaging (MRI) are considered critical for diagnosis of LMD. It has been s...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-007-9493-1
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:In most patients with recurrent glioma chemotherapy is the only remaining treatment option. In general results of chemotherapy in these patients are poor, and trials on new regimens are indicated. Because relatively good results have been achieved with combinations of platin compounds and etoposide, we inves...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1023/a:1006201909435
更新日期:1999-08-01 00:00:00
abstract:INTRODUCTION:Erlotinib and Gefitinib (EGFRi) are small molecules specifically inhibiting epidermal growth factor receptor (EGFR). We present here data of an exploratory study evaluating EGFRi monotherapy in patients with recurrent or progressive malignant glioma. PATIENTS:21 patients with recurrent or progressive mali...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1007/s11060-008-9608-3
更新日期:2008-09-01 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
abstract::To increase awareness about lymphomatosis cerebri by describing a patient with a unique presentation Case report a 58 year old woman presented with progressive lower extremity weakness, postural hypotension, and 90 pound weight loss over 3 months a brain magnetic resonance image revealed multiple non-enhancing foci of...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-012-0931-3
更新日期:2012-09-01 00:00:00