Abstract:
OBJECT:Etoposide, a topoisomerase-II inhibitor promotes DNA damage and apoptosis of cancer cells. In this study, we have examined the ability of the histone deacetylase inhibitor, valproic acid (VPA) to modulate gene expression and sensitize glioblastoma cell lines to the cytotoxic effects of etoposide in vitro. METHODS:The effect of VPA and etoposide alone or a combination of the two drugs on the growth of three different glioblastoma cell lines (U87, LN18, and U251) were measured by MTT assays. Drug treated cells were analyzed for their cell cycle profile, gene expression, differentiation status, and induction of apoptosis by flow-cytometry, western blotting, immunofluorescence assays, and caspase activity measurements. RESULTS:We observed that while VPA and etoposide independently inhibited the growth of U87, U251, and LN18 cells, exposure of tumor cells to both drugs significantly enhanced the cytotoxicity of etoposide in all cell lines. VPA promoted a G(1) accumulation of U87, while an increase in the G(2)/M population of U251 and LN18 cells was observed upon exposure to the drug. Treatment with etoposide resulted in a G(2)/M arrest of U87, U251, and LN18 cells, whereas, exposure to both drugs increased the fraction of cells with a G2/M and sub-G1 DNA content. Further, VPA and not etoposide, promoted acetylation of histone H4 and induced the expression of the cyclin-dependent kinase inhibitor (CDKI), p21/WAF1. VPA also up-regulated the expression of the alpha and beta isoforms of topoisomerase-II, as well as the glial differentiation marker, glial fibrillary acidic protein. Finally, a significant increase in caspase-3 activity and apoptosis was observed in the presence of both VPA and etoposide compared to either agent alone. CONCLUSION:Our study demonstrates that VPA sensitizes U87, U251, and LN18 cells to the cytotoxic effects of etoposide in vitro by inducing differentiation and up-regulating the expression of p21/WAF1 and both isoforms of topoisomerase-II.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Das CM,Aguilera D,Vasquez H,Prasad P,Zhang M,Wolff JE,Gopalakrishnan Vdoi
10.1007/s11060-007-9402-7subject
Has Abstractpub_date
2007-11-01 00:00:00pages
159-70issue
2eissn
0167-594Xissn
1573-7373journal_volume
85pub_type
杂志文章abstract::Glioblastoma cells secrete transforming growth factor-beta (TGF-beta), which has a variety of immunosuppressive properties. We investigated the effect of irradiation TGF-beta secretion by malignant glioma cells. Three malignant glioma cell lines (T98G, A172, KG-1-C) were cultured and irradiated using 10 and 50 Gy Lina...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005791621265
更新日期:1997-07-01 00:00:00
abstract::Twenty-eight patients with malignant brain tumors (16 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation with or without chemotherapy received varying doses of intracarotid VP-16. Courses of therapy were repeated every 4 weeks along with computerized axial tomography scan and...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00195611
更新日期:1987-01-01 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::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::It is unknown whether the addition of temozolomide (TMZ) to radiotherapy (RT) is associated with improved overall survival (OS) among older glioblastoma patients. We performed a retrospective cohort SEER-Medicare analysis of 1652 patients aged ≥65 years with glioblastoma who received ≥10 fractions of RT from 2005 to 2...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2294-7
更新日期:2017-01-01 00:00:00
abstract::Steroids are beneficial in neurological illness, but have many serious side effects. Having observed several patients with severe steroid psychoses, which greatly prolonged their hospitalizations, the authors sought to improve understanding of this entity. A literature review was conducted. The incidence of severe psy...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-012-0919-z
更新日期:2012-09-01 00:00:00
abstract:PURPOSE:Outcomes for patients with recurrent high-grade glioma (HGG) progressing on bevacizumab (BEV) are dismal. Fractionated stereotactic radiosurgery (FSRS) has been shown to be feasible and safe when delivered in this setting, but prospective evidence is lacking. This single-institution randomized trial compared FS...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-020-03526-4
更新日期:2020-06-01 00:00:00
abstract::Mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) have been identified in approximately 70-80 % of astrocytomas and oligodendrogliomas of WHO grades II and III, and in secondary glioblastomas. In addition, a low incidence of IDH2 mutations has been detected in these tumors, and the occurence of IDH1 and...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-012-0863-y
更新日期:2012-08-01 00:00:00
abstract:PURPOSE:The purpose of this study is to describe the long-term toxicities of intracranial germ cell tumor (IGCT) in the adolescent and young adult (AYA) population. METHODS:We report late toxicities of a multi-center cohort of AYA patients treated for IGCT between 1975 and 2015. Charts were retrospectively reviewed fo...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-020-03642-1
更新日期:2020-09-01 00:00:00
abstract::Compared to classical oncological outcome measures such as time to progression and survival, the importance of cognitive functioning in patients with diffuse infiltrative brain tumors has only recently been recognized. Apart from the relatively low incidence and the invariably fatal outcome of gliomas, the general ass...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-012-0811-x
更新日期:2012-06-01 00:00:00
abstract::In a cohort of 25 patients with supratentorial low grade glioma, the timing of radiotherapy made no significance difference for 10 year survival. Patients who received early radiotherapy had a 55% 10 year survival and those receiving delayed radiotherapy had a 53% 10 year survival. Radiotherapy was delayed a median of...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005703102687
更新日期:1997-08-01 00:00:00
abstract::To date, no histopathological vascular investigation focusing on peritumoral brain zone (PBZ) has been reported for glioblastoma. We analyzed 10 newly diagnosed cases of glioblastomas. For these PBZs, histopathological investigation was performed by hematoxylin-eosin (H&E) staining and immunohistochemistry was analyze...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2648-9
更新日期:2018-01-01 00:00:00
abstract::Cyclin-dependent kinase 4 inhibitor (CDKN2/p16) is a cell cycle regulatory protein that has been demonstrated to be inactivated by mutations, deletions or transcriptional silencing during pathogenesis of a variety of human malignancies. We studied the correlation of CDKN2/p16 expression with cell proliferation activit...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1006185220369
更新日期:1999-02-01 00:00:00
abstract:OBJECTIVE:To evaluate perioperative management, early outcomes and hemocoagulative disorders in infants up to 1 year old, undergoing neurosurgery for brain tumors removal. DESIGN:Retrospective evaluation of prospectively collected data regarding all infants aged <1 year admitted to PICU from 1994 to 2004, following in...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9643-0
更新日期:2008-11-01 00:00:00
abstract::High expression of ERBB2 has been reported in medulloblastoma and ependymoma; EGFR is amplified and over-expressed in brainstem glioma suggesting these proteins as potential therapeutic targets. We conducted a molecular biology (MB) and phase II study to estimate inhibition of tumor ERBB signaling and sustained respon...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s11060-013-1166-7
更新日期:2013-09-01 00:00:00
abstract::Treatment for anaplastic astrocytoma (AA) is controversial. To assess three primary treatment approaches, patients from a single institution were retrospectively evaluated. To represent modern treatment selection, patients diagnosed with AA from December 2003 to December 2009 were selected. Those with insufficient dat...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-013-1116-4
更新日期:2013-06-01 00:00:00
abstract::Thirty-one patients with metastatic brain tumors that either failed to respond or recurred after conventional therapy were treated by intra-arterial infusion of 100 mg/m2 of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) into either a carotid or vertebral artery. Five patients (three with lung cancer, one with breast can...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00165605
更新日期:1983-01-01 00:00:00
abstract::Ependymoma is the third most common brain tumor in children, but there is a paucity of large studies with more than 10 years of follow-up examining the long-term survival and recurrence patterns of this disease. We conducted a retrospective chart review of 103 pediatric patients with WHO Grades II/III intracranial epe...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1007/s11060-017-2568-8
更新日期:2017-10-01 00:00:00
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 ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2819-3
更新日期:2018-07-01 00:00:00
abstract::Adrenomedullin is a vasoactive peptide that is upregulated in higher-grade gliomas and promotes tumor cell proliferation. Since reduced activity of the anti-oncogene PTEN seems to also correlate with higher tumor grade, this suggests an inverse association between PTEN activity and adrenomedullin expression. PC12 pheo...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-005-9035-7
更新日期:2006-09-01 00:00:00
abstract::Primary brain tumor patients experience high levels of distress. The purpose of this cross-sectional, retrospective study is to evaluate the level and different sources of psychosocial distress and how these pertain to health-related quality of life (HRQoL). The Primary and Recurrent Glioma registry at Duke's The Pres...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2535-4
更新日期:2017-09-01 00:00:00
abstract::Cancer metastasis can affect any part of the nervous system. When the peripheral nervous system is involved, the usual targets are cranial nerves, nerve roots and plexi. However, peripheral nerves and muscles can also be affected by compression or infiltration of neoplastic cells. This review focuses in the diagnosis ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-004-8102-9
更新日期:2005-10-01 00:00:00
abstract::Future success using chemotherapy against human gliomas may result from exploiting unique molecular vulnerabilities of these tumors. Chemotherapy frequently results in DNA damage. When such damage is sensed by the cell, programmed cell death, or apoptosis, may be initiated. However, chemotherapy-induced DNA damage may...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1022554824129
更新日期:2003-02-01 00:00:00
abstract::Intravascular lymphomatosis (IL) is a rare entity only recently included in lymphoma classification, whose main feature is the exclusive or predominant growth of neoplastic cells within blood vessels. The vast majority of the patients affected by IL belong to the 7th or 8th decade of life and present with skin rash or...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1006476701534
更新日期:2001-01-01 00:00:00
abstract::Glioblastoma multiforme (GBM) represents a class of malignant gliomas which rapidly proliferate, invade and destroy surrounding brain tissues. This study examined micro-RNA (miRNA) speciation and miRNA effects on gene expression in six ATCC glioma and GBM cell lines and in 14 glioma and GBM samples obtained from human...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9688-0
更新日期:2009-01-01 00:00:00
abstract::Approximately 200,000 men will be diagnosed with prostate cancer in 1994. While localized disease is potentially curable with surgery or radiation therapy, metastatic disease is incurable. The most frequent site of metastasis is bone. Spinal cord compression occurs in approximately 7% of men with prostate cancer. Back...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/BF01053418
更新日期:1995-01-01 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::Medulloblastomas are the most common malignant brain tumors in childhood. Emerging evidence suggests that medulloblastoma comprises at least four distinct diseases (WNT, SHH, Group 3 and 4) with different biology, clinical presentation, and outcome, with especially poor prognosis in Group 3. The tight connection of bi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-012-0978-1
更新日期:2012-12-01 00:00:00
abstract::To evaluate diagnostic accuracy of perfusion weighted imaging (PWI) and positron emission tomography (PET) using an integrated PET/MR system in tumor grading as well as in differentiating recurrent tumor from treatment-induced effects (TIE) in brain tumor patients. Twenty patients (Group A: treatment naïve, 9 patients...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-2032-6
更新日期:2016-04-01 00:00:00
abstract::This case study describes the long-term course of behavioral alterations and MRI findings in a patient with a combined limbic and cerebellar paraneoplastic syndrome, which was associated with a squamous lung carcinoma. Clinical equivalents were cerebellar ataxia, as well as severe anterograde memory loss, frontal exec...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/b:neon.0000013488.52742.b4
更新日期:2004-01-01 00:00:00