Abstract:
:ATP-binding cassette transporters (ABC transporters) regulate traffic of multiple compounds, including chemotherapeutic agents, through biological membranes. They are expressed by multiple cell types and have been implicated in the drug resistance of some cancer cells. Despite significant research in ABC transporters in the context of many diseases, little is known about their expression and clinical value in glioblastoma (GBM). We analyzed expression of 49 ABC transporters in both commercial and patient-derived GBM cell lines as well as from 51 human GBM tumor biopsies. Using The Cancer Genome Atlas (TCGA) cohort as a training dataset and our cohort as a validation dataset, we also investigated the prognostic value of these ABC transporters in newly diagnosed GBM patients, treated with the standard of care. In contrast to commercial GBM cell lines, GBM-patient derived cell lines (PDCL), grown as neurospheres in a serum-free medium, express ABC transporters similarly to parental tumors. Serum appeared to slightly increase resistance to temozolomide correlating with a tendency for an increased expression of ABCB1. Some differences were observed mainly due to expression of ABC transporters by microenvironmental cells. Together, our data suggest that the efficacy of chemotherapeutic agents may be misestimated in vitro if they are the targets of efflux pumps whose expression can be modulated by serum. Interestingly, several ABC transporters have prognostic value in the TCGA dataset. In our cohort of 51 GBM patients treated with radiation therapy with concurrent and adjuvant temozolomide, ABCA13 overexpression is associated with a decreased progression free survival in univariate (p < 0.01) and multivariate analyses including MGMT promoter methylation (p = 0.05) suggesting reduced sensitivity to temozolomide in ABCA13 overexpressing GBM. Expression of ABC transporters is: (i) detected in GBM and microenvironmental cells and (ii) better reproduced in GBM-PDCL. ABCA13 expression is an independent prognostic factor in newly diagnosed GBM patients. Further prospective studies are warranted to investigate whether ABCA13 expression can be used to further personalize treatments for GBM.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Dréan A,Rosenberg S,Lejeune FX,Goli L,Nadaradjane AA,Guehennec J,Schmitt C,Verreault M,Bielle F,Mokhtari K,Sanson M,Carpentier A,Delattre JY,Idbaih Adoi
10.1007/s11060-018-2819-3subject
Has Abstractpub_date
2018-07-01 00:00:00pages
479-486issue
3eissn
0167-594Xissn
1573-7373pii
10.1007/s11060-018-2819-3journal_volume
138pub_type
杂志文章abstract::Glioblastoma (GBM) is a highly aggressive brain tumor for which novel therapeutic approaches, such as immunotherapy, are urgently needed. Zoledronate (ZOL), an inhibitor of osteoclastic activity, is known to stimulate peripheral blood-derived γδT cells and sensitize tumors to γδT cell-mediated killing. To investigate ...
journal_title:Journal of neuro-oncology
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doi:10.1007/s11060-013-1258-4
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abstract::Tripartite motif (TRIM) proteins are involved in tumorigenesis. Here, we examined the expression, biological function, and clinical significance of tripartite motif containing 28 (TRIM28) in glioma, a locally aggressive brain tumor. First, TRIM28 expression was significantly higher in glioma (n = 138) than in non-glio...
journal_title:Journal of neuro-oncology
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abstract:UNLABELLED:Cranio-spinal irradiation is the gold standard treatment used in non metastatic medulloblastoma as prophylaxis against central nervous system (CNS) metastases. However, given the severe late effects caused by this procedure in children under 3 years of age, most pediatric oncologists are currently treating t...
journal_title:Journal of neuro-oncology
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doi:10.1007/BF00146088
更新日期:1996-01-01 00:00:00
abstract::Pituitary metastases are uncommon, ranging from 1 to 5 % of all metastases. Between 10 and 30 % of pituitary lesions are symptomatic responsible for diabetes insipidus, visual field defect or cranial nerve palsy. Primary sites are lung or breast in two-thirds of cases. There is no current reference concerning treatmen...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1967-y
更新日期:2016-01-01 00:00:00
abstract::p53 mutations are the most frequently detected genetic alterations of gliomas, appearing in a similar proportion of low and high grade astrocytomas, while the amplification of epidermal growth factor receptor (EGFR) gene appears mainly in glioblastomas. Thus, these changes seem to delineate two subgroups of high grade...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF01054764
更新日期:1995-10-01 00:00:00
abstract::The effect of recombinant human interleukin 1 beta (rHuIL-1 beta) on myelosuppression induced by 3-[(4-amino-2-methyl-5-pyrimidynyl)methyl]-1-(2-chloroethyl)-1-nit rosourea hydrochloride (ACNU) was studied. In in vivo study using BALB/c mice, pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single intraperiton...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00177620
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abstract::Medulloblastoma with melanotic differentiation, a rare variant of medulloblastoma, often carries a poor prognosis. We present such a case of a 4 year male with this rare, aggressive tumor. Additionally, we have reviewed the literature and report on the features important in the pathologic and radiologic diagnosis in t...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-010-0436-x
更新日期:2011-07-01 00:00:00
abstract::When a malignant tumor invades the child's cerebellum, the cost of successful treatment is often significant cognitive morbidity. A review of neuropsychological outcome revealed that survivors of childhood medulloblastoma (MB) have long-term deficits in intelligence, memory, language, attention, academic skills, psych...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00165522
更新日期:1996-07-01 00:00:00
abstract::While surgery is proned in low-grade glioma (LGG), the invasion of functional areas frequently prevents a complete resection. We report the first case of a patient operated on for a left frontal LGG, diagnosed because of seizures, with partial resection due to an invasion of the controlateral hemisphere. Chemotherapy ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-006-9168-3
更新日期:2006-11-01 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::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: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::Central nervous system (CNS) involvement is a rare complication of chronic lymphocytic leukemia (CLL) with varied outcomes. We contribute two additional cases of CLL with CNS involvement. The clinical course and response to treatment are described. All 78 previously reported cases of CLL with CNS involvement are prese...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-011-0636-z
更新日期:2012-01-01 00:00:00
abstract::The aim of the present study was to investigate the localization and distribution of the putative brain tumour stem cell marker CD133 in formalin fixed paraffin embedded astrocytomas. A retrospective analysis of 114 grade II, III and IV astrocytomas was undertaken. The immunohistochemical expression of CD133 in paraff...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9648-8
更新日期:2008-11-01 00:00:00
abstract:PURPOSE:To analyze patterns of failure according to treatment modalities and evaluate the adequacy of an institution's current volume of postoperative radiotherapy (PORT) for World Health Organization (WHO) grade II or III meningiomas. PATIENTS AND METHODS:Data of 98 patients treated by either surgery and PORT (PORT g...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03232-w
更新日期:2019-09-01 00:00:00
abstract::Disparities in American health care based on socially-defined patient characteristics such as race, ethnicity, and socioeconomic position are well-documented. We review differences and disparities in incidence, pathobiology, processes and outcomes of care, and survival based on social factors for brain tumors of all h...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-009-9840-5
更新日期:2009-05-01 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::Pituitary adenomas produce the chemokine stromal cell-derived factor (SDF-1α/CXCL12) and its receptor, CXCR4. A recent study indicated that CXCL12 and CXCR4 are concomitantly up-regulated in hypoxia. The objective of this study was to analyze the molecular mechanism of hypoxia-mediated CXCR4 up-regulation and assess t...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-010-0152-6
更新日期:2010-10-01 00:00:00
abstract::Treatment of recurrent primary CNS lymphoma (PCNSL) though not standardized most often utilizes whole brain radiotherapy, re-challenge with high-dose methotrexate, or administration of an alkylating chemotherapy. High-dose cytarabine (HD-araC) has been advocated as an active agent in PCNSL but limited information exis...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1994-8
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abstract::Anaplastic oligodendroglioma (AO) is an uncommon intracranial tumor and prognosis is poor. In this study, we assessed the factors affecting the prognosis of AO patients. Seventy AO patients were recruited from 2001 to 2006 in Shanghai Huashan Hospital of Fudan University; all were treated surgically. Kaplan-Meier surv...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
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abstract:SUBJECT:To date there is no established tumor marker for the clinical follow-up of glioblastoma, WHO grade IV, (GBM) which constitutes the most frequent and malignant primary brain tumor. However, since there is promising data that the serum glial fibrillary acidic protein (sGFAP) may serve as a biomarker for glial bra...
journal_title:Journal of neuro-oncology
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更新日期:2018-09-01 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::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::Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, malignant brain tumors which occur almost exclusively in infants and young children. There have been only 17 cases of AT/RT in adults reported in the medical literature and the rarity of this tumor makes the diagnosis in adults difficult. We describe a case of an AT...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-007-9339-x
更新日期:2007-08-01 00:00:00
abstract::Lonidamine (LND) has been shown to inhibit tumor aerobic glycolysis. Its effect was evaluated on several human astrocytomas at different degrees of malignancy; a correlation was found between LDN effect on lactate production and tumor malignancy: in grade I and II astrocytomas LND stimulates lactate production, while ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00163702
更新日期:1988-11-01 00:00:00
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::During photodynamic therapy (PDT) both normal and pathological brain tissue, in close proximity to the light source, can experience significant temperature increases. The purpose of this study was to investigate the anti-tumor effects of concurrent 5-aminolevulinic acid (ALA)-mediated PDT and hyperthermia (HT) in huma...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-004-9161-7
更新日期:2004-12-01 00:00:00
abstract::In the treatment of malignant glioma, chemotherapy plays a critical role as do surgical resection and irradiation. Cepharanthine (CEP), a biscoclaurine-derived alkaloid, reportedly potentiates the effects of antitumor agents and induces apoptosis in some cancer cells. Here, we examined the effects of CEP, alone and in...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1014548618440
更新日期:2002-01-01 00:00:00
abstract::In earlier studies, we demonstrated that intratumoral infusions of alloreactive cytotoxic T lymphocytes (aCTL), sensitized to the major histocompatibility complex (MHC) antigens of the host, effectively retarded the intracranial growth of Fischer 9L gliosarcoma. We further demonstrated that continuous in vitro exposur...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF02700024
更新日期:2003-08-01 00:00:00
abstract::Primary intramedullary spinal cord tumors are a rare entity, comprising 4–10 %of all spinal cord tumors. The current report presents data on intramedullary spinal cord anaplastic astrocytomas and glioblastomas in adults using the national surveillance, epidemiology, and end results database (1973–2008), and evaluates ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-013-1296-y
更新日期:2013-12-01 00:00:00