REV3L confers chemoresistance to cisplatin in human gliomas: the potential of its RNAi for synergistic therapy.

Abstract:

:The REV3L gene, encoding the catalytic subunit of human polymerase zeta, plays a significant role in the cytotoxicity, mutagenicity, and chemoresistance of certain tumors. However, the role of REV3L in regulating the sensitivity of glioma cells to chemotherapy remains unknown. In this study, we investigated the expression of the REV3L gene in 10 normal brain specimens and 30 human glioma specimens and examined the value of REV3L as a potential modulator of cellular response to various DNA-damaging agents. Reverse transcriptase PCR/real-time PCR analysis revealed that REV3L was overexpressed in human gliomas compared with normal brain tissues. A glioma cell model with stable overexpression of REV3L was used to probe the role of REV3L in cisplatin treatment; upregulation of REV3L markedly attenuated cisplatin-induced apoptosis of the mitochondrial apoptotic pathway. We therefore assessed the REV3L-targeted treatment modality that combines suppression of REV3L expression using RNA interference (RNAi) with the cytotoxic effects of DNA-damaging agents. Downregulation of REV3L expression significantly enhanced the sensitivity of glioma cells to cisplatin, as evidenced by the increased apoptosis rate and marked alterations in the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) and proapoptotic Bcl-2-associated x protein (Bax) expression levels, and reduced mutation frequencies in surviving glioma cells. These results suggest that REV3L may potentially contribute to gliomagenesis and play a crucial role in regulating cellular response to the DNA cross-linking agent cisplatin. Our findings indicate that RNAi targeting REV3L combined with chemotherapy has synergistic therapeutic effects on glioma cells, which warrants further investigation as an effective novel therapeutic regimen for patients with this malignancy.

journal_name

Neuro Oncol

journal_title

Neuro-oncology

authors

Wang H,Zhang SY,Wang S,Lu J,Wu W,Weng L,Chen D,Zhang Y,Lu Z,Yang J,Chen Y,Zhang X,Chen X,Xi C,Lu D,Zhao S

doi

10.1215/15228517-2009-015

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

790-802

issue

6

eissn

1522-8517

issn

1523-5866

pii

15228517-2009-015

journal_volume

11

pub_type

杂志文章
  • Survivorship care planning and implementation in neuro-oncology.

    abstract::Survivorship has become a significant topic within oncologic care. The tools and means by which the provision of survivorship care can be implemented and delivered are in development and are the focus of significant research oncology-wide. These tools and methods include innovations of survivorship care delivery, surv...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noy110

    authors: Leeper H,Milbury K

    更新日期:2018-11-09 00:00:00

  • Inhibition of EZH2 suppresses self-renewal and induces radiation sensitivity in atypical rhabdoid teratoid tumor cells.

    abstract:INTRODUCTION:Overexpression of the Polycomb repressive complex 2 (PRC2) subunit Enhancer of Zeste 2 (EZH2) occurs in several malignancies, including prostate cancer, breast cancer, medulloblastoma, and glioblastoma multiforme. Recent evidence suggests that EZH2 may also have a role in rhabdoid tumors. Atypical teratoid...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nos285

    authors: Alimova I,Birks DK,Harris PS,Knipstein JA,Venkataraman S,Marquez VE,Foreman NK,Vibhakar R

    更新日期:2013-02-01 00:00:00

  • Imaging of brain and brain tumor specimens by time-resolved multiphoton excitation microscopy ex vivo.

    abstract::Multiphoton excitation fluorescent microscopy is a laser-based technology that allows subcellular resolution of native tissues in situ. We have recently applied this technology to the structural and photochemical imaging of cultured glioma cells and experimental gliomas ex vivo. We demonstrated that high microanatomic...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2006-034

    authors: Kantelhardt SR,Leppert J,Krajewski J,Petkus N,Reusche E,Tronnier VM,Hüttmann G,Giese A

    更新日期:2007-04-01 00:00:00

  • Cisplatin-induced peripheral neuropathy is associated to neuronal senescence-like response.

    abstract:BACKGROUND:Cisplatin-Induced Peripheral Neuropathy (CIPN) is a frequent serious dose-dependent adverse event that can determine dosage limitations for cancer treatment. CIPN severity correlates with the amount of platinum detected in sensory neurons of the dorsal root ganglia (DRG). However, the exact pathophysiology o...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noaa151

    authors: Calls A,Torres-Espin A,Navarro X,Yuste VJ,Udina E,Bruna J

    更新日期:2020-06-29 00:00:00

  • PARP mediated PARylation of MGMT is critical to promote repair of temozolomide-induced O6-methylguanine DNA damage in glioblastoma.

    abstract:BACKGROUND:Temozolomide (TMZ) resistance in Glioblastoma (GBM) is mediated by the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). MGMT promoter methylation (occurs in about 40% patients) is associated with loss of MGMT expression (MGMT-) that compromises DNA repair, leading to a favorable response to ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noab003

    authors: Wu S,Li X,Gao F,de Groot JF,Koul D,Yung WKA

    更新日期:2021-01-12 00:00:00

  • Apparent diffusion coefficient histogram metrics correlate with survival in diffuse intrinsic pontine glioma: a report from the Pediatric Brain Tumor Consortium.

    abstract:BACKGROUND:Diffuse intrinsic pontine glioma (DIPG) is associated with poor survival regardless of therapy. We used volumetric apparent diffusion coefficient (ADC) histogram metrics to determine associations with progression-free survival (PFS) and overall survival (OS) at baseline and after radiation therapy (RT). MET...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nov256

    authors: Poussaint TY,Vajapeyam S,Ricci KI,Panigrahy A,Kocak M,Kun LE,Boyett JM,Pollack IF,Fouladi M

    更新日期:2016-05-01 00:00:00

  • Brain tumor eradication and prolonged survival from intratumoral conversion of 5-fluorocytosine to 5-fluorouracil using a nonlytic retroviral replicating vector.

    abstract::Patients with the most common and aggressive form of high-grade glioma, glioblastoma multiforme, have poor prognosis and few treatment options. In 2 immunocompetent mouse brain tumor models (CT26-BALB/c and Tu-2449-B6C3F1), we showed that a nonlytic retroviral replicating vector (Toca 511) stably delivers an optimized...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor199

    authors: Ostertag D,Amundson KK,Lopez Espinoza F,Martin B,Buckley T,Galvão da Silva AP,Lin AH,Valenta DT,Perez OD,Ibañez CE,Chen CI,Pettersson PL,Burnett R,Daublebsky V,Hlavaty J,Gunzburg W,Kasahara N,Gruber HE,Jolly DJ,Robb

    更新日期:2012-02-01 00:00:00

  • Age and DNA methylation subgroup as potential independent risk factors for treatment stratification in children with atypical teratoid/rhabdoid tumors.

    abstract:BACKGROUND:Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with atypical teratoid/rhabdoid tumors (ATRTs). The European Rhabdoid Registry (EU-RHAB) recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. METH...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noz244

    authors: Frühwald MC,Hasselblatt M,Nemes K,Bens S,Steinbügl M,Johann PD,Kerl K,Hauser P,Quiroga E,Solano-Paez P,Biassoni V,Gil-da-Costa MJ,Perek-Polnik M,van de Wetering M,Sumerauer D,Pears J,Stabell N,Holm S,Hengartner H,Ge

    更新日期:2020-07-07 00:00:00

  • Prognostic significance of the aggregative perivascular growth pattern of tumor cells in primary central nervous system diffuse large B-cell lymphoma.

    abstract:BACKGROUND:Primary central nervous system lymphomas, predominantly diffuse large B-cell lymphomas (PCNS-DLBCL), are aggressive malignancies, and no histopathological variables with independent prognostic value are currently available. The aim of this study is to determine the prognostic value of histopathological varia...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not012

    authors: He M,Zuo C,Wang J,Liu J,Jiao B,Zheng J,Cai Z

    更新日期:2013-06-01 00:00:00

  • Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries.

    abstract::The exact incidence of pineal germ-cell tumors is largely unknown. The tumors are rare, and the number of patients with these tumors, as reported in clinical series, has been limited. The goal of this study was to describe pineal germ-cell tumors in a large number of patients, using data from available brain tumor dat...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2007-054

    authors: Villano JL,Propp JM,Porter KR,Stewart AK,Valyi-Nagy T,Li X,Engelhard HH,McCarthy BJ

    更新日期:2008-04-01 00:00:00

  • Positron emission tomography-guided conformal fast neutron therapy for glioblastoma multiforme.

    abstract::Glioblastoma multiforme (GBM) continues to be a difficult therapeutic challenge. Our study was conducted to determine whether improved survival and tumor control could be achieved with modern delivery of fast neutron radiation using three-dimensional treatment planning. Ten patients were enrolled. Eligibility criteria...

    journal_title:Neuro-oncology

    pub_type: 临床试验,杂志文章

    doi:10.1215/15228517-2007-044

    authors: Stelzer KJ,Douglas JG,Mankoff DA,Silbergeld DL,Krohn KA,Laramore GE,Spence AM

    更新日期:2008-02-01 00:00:00

  • Dissecting inherent intratumor heterogeneity in patient-derived glioblastoma culture models.

    abstract:Background:Molecular profile of glioblastoma multiforme (GBM) revealed 4 subtypes, 2 of which, proneural and mesenchymal, have been predominantly observed, with the latter displaying a more aggressive phenotype and increased therapeutic resistance. Single-cell RNA sequencing revealed that multiple subtypes actually res...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/now253

    authors: Teng J,da Hora CC,Kantar RS,Nakano I,Wakimoto H,Batchelor TT,Chiocca EA,Badr CE,Tannous BA

    更新日期:2017-06-01 00:00:00

  • Updates in the management of brain metastases.

    abstract::The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survi...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/now127

    authors: Arvold ND,Lee EQ,Mehta MP,Margolin K,Alexander BM,Lin NU,Anders CK,Soffietti R,Camidge DR,Vogelbaum MA,Dunn IF,Wen PY

    更新日期:2016-08-01 00:00:00

  • Predictors of leptomeningeal disease following hypofractionated stereotactic radiotherapy for intact and resected brain metastases.

    abstract:BACKGROUND:The objective was to evaluate the risk and predictors of developing leptomeningeal disease (LMD) in patients with brain metastases treated with 5-fraction hypofractionated stereotactic radiotherapy (HSRT). METHODS:Patients treated with HSRT for intact brain metastases and/or surgical cavities were reviewed ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noz144

    authors: Nguyen TK,Sahgal A,Detsky J,Atenafu EG,Myrehaug S,Tseng CL,Husain Z,Heyn C,Maralani P,Ruschin M,Perry J,Soliman H

    更新日期:2020-01-11 00:00:00

  • Convection-enhanced delivery of Ls-TPT enables an effective, continuous, low-dose chemotherapy against malignant glioma xenograft model.

    abstract::Treatment of malignant gliomas represents one of the most formidable challenges in oncology. The combination of surgery, radiation, and chemotherapy yields median survivals of less than one year. Here we demonstrate the use of a minimally invasive surgical technique, convection-enhanced delivery (CED), for local admin...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2006-001

    authors: Saito R,Krauze MT,Noble CO,Drummond DC,Kirpotin DB,Berger MS,Park JW,Bankiewicz KS

    更新日期:2006-07-01 00:00:00

  • Low-dose fractionated radiotherapy and concomitant chemotherapy in glioblastoma multiforme with poor prognosis: a feasibility study.

    abstract::We explored the feasibility of concurrent palliative chemotherapy and low-dose fractionated radiotherapy (LD-FRT) in glioblastoma multiforme (GBM). Patients with recurrent/progressive GBM at least 3 months after the end of primary radiotherapy received 0.3 Gy twice daily with cisplatin and fotemustine if progressing o...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor173

    authors: Balducci M,Chiesa S,Diletto B,D'Agostino GR,Mangiola A,Manfrida S,Mantini G,Albanese A,Fiorentino A,Frascino V,De Bari B,Micciche' F,De Rose F,Morganti AG,Anile C,Valentini V

    更新日期:2012-01-01 00:00:00

  • Paraneoplastic chorea: case study with autopsy confirmation.

    abstract::A 67-year-old man presented with a 7-month history of insidiously progressive chorea, ataxia, and vertigo. Neurologic examination revealed deficits referable to the basal nuclei, cerebellar vermis, and vestibular nuclei. Small-cell lung cancer was diagnosed by fine-needle biopsy of a parahilar mass. After chemotherapy...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/4.3.192

    authors: Tremont-Lukats IW,Fuller GN,Ribalta T,Giglio P,Groves MD

    更新日期:2002-07-01 00:00:00

  • Viral and other therapies for recurrent glioblastoma: is a 24-month durable response unusual?

    abstract::A phase I trial of an engineered poliovirus for the treatment of recurrent glioblastoma (GBM) has attracted attention due to 8 survivors reaching the 24-month and 5 reaching the 36-month survival landmarks.1 Genetically engineered viruses (oncolytic viruses) have been in trials for GBM for almost two decades.2 These r...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/noy170

    authors: Chiocca EA,Nassiri F,Wang J,Peruzzi P,Zadeh G

    更新日期:2019-01-01 00:00:00

  • Long-term outcomes of surgical resection with or without adjuvant radiation therapy for treatment of spinal ependymoma: a retrospective multicenter study by the Korea Spinal Oncology Research Group.

    abstract:BACKGROUND:We sought to determine the surgical treatment and functional outcome and identify the predictors of survival in a retrospective cohort of patients with spinal cord ependymoma using data collected from the Korea Spinal Oncology Research Group database. METHODS:The data regarding 88 patients who had been surg...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1093/neuonc/not038

    authors: Lee SH,Chung CK,Kim CH,Yoon SH,Hyun SJ,Kim KJ,Kim ES,Eoh W,Kim HJ

    更新日期:2013-07-01 00:00:00

  • Descriptive epidemiology of CNS tumors in France: results from the Gironde Registry for the period 2000-2007.

    abstract::An increase in the incidence of CNS tumors has been observed in many countries in the last decades. The reality of this trend has been much debated, as it has happened during a period when computer-assisted tomography and MRI have dramatically improved the detection of these tumors. The Gironde CNS Tumor Registry prov...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor120

    authors: Baldi I,Gruber A,Alioum A,Berteaud E,Lebailly P,Huchet A,Tourdias T,Kantor G,Maire JP,Vital A,Loiseau H,Gironde TSNC Registry Group.

    更新日期:2011-12-01 00:00:00

  • Brain cancer mortality in the United States, 1986 to 1995: a geographic analysis.

    abstract::The Atlas of Cancer Mortality in the United States, 1950-94 (Devesa et al.) published in 1999 by the National Institutes of Health suggests that there are elevated rates of brain and other nervous system cancer in the northwestern, north central, and southeastern parts of the country. Being descriptive in nature, the ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/S1152851703000450

    authors: Fang Z,Kulldorff M,Gregorio DI

    更新日期:2004-07-01 00:00:00

  • Phase II preradiation R115777 (tipifarnib) in newly diagnosed GBM with residual enhancing disease.

    abstract::Glioblastoma multiforme (GBM) is a lethal primary malignant brain tumor in adults. R115777 (tipifarnib) is an oral agent with antiproliferative effects, being a potent and selective inhibitor of farnesyltransferase. This multicenter, open-label phase II study was designed to evaluate the efficacy and safety of R115777...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1215/15228517-2008-070

    authors: Lustig R,Mikkelsen T,Lesser G,Grossman S,Ye X,Desideri S,Fisher J,Wright J,New Approaches to Brain Tumor Therapy CNS Consortium.

    更新日期:2008-12-01 00:00:00

  • Invasion patterns in brain metastases of solid cancers.

    abstract:BACKGROUND:Brain metastases are generally considered to be well demarcated from the surrounding brain parenchyma, although infiltrative growth patterns have been observed. We systemically investigated infiltration patterns and expression of adhesion molecules in a large and well-defined series of autopsy cases of brain...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not112

    authors: Berghoff AS,Rajky O,Winkler F,Bartsch R,Furtner J,Hainfellner JA,Goodman SL,Weller M,Schittenhelm J,Preusser M

    更新日期:2013-12-01 00:00:00

  • Practice changing mature results of RTOG study 9802: another positive PCV trial makes adjuvant chemotherapy part of standard of care in low-grade glioma.

    abstract::The long-term follow-up of the RTOG 9802 trial that compared 54 Gy of radiotherapy (RT) with the same RT followed by adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy in high-risk low-grade glioma shows a major increase in survival after adjuvant PCV chemotherapy. Median overall survival increased from 7...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/nou297

    authors: van den Bent MJ

    更新日期:2014-12-01 00:00:00

  • Increases in the number of brain metastases detected at frame-fixed, thin-slice MRI for gamma knife surgery planning.

    abstract::For gamma knife planning, 2.4-mm-slice MRIs are taken under rigid frame fixation, so tiny tumors become visible. This study evaluated differences in the numbers of brain metastases between conventional contrast-enhanced MRI (6 ± 1 mm slice thickness) taken before patient referral and contrast-enhanced MRI for gamma kn...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noq084

    authors: Nagai A,Shibamoto Y,Mori Y,Hashizume C,Hagiwara M,Kobayashi T

    更新日期:2010-11-01 00:00:00

  • Prognostic awareness, prognostic communication, and cognitive function in patients with malignant glioma.

    abstract:Background:Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and shortened life expectancy (LE). Accurate PA is associated with favorable psychological outcomes at the end of life (EoL) for patients with ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nox117

    authors: Diamond EL,Prigerson HG,Correa DC,Reiner A,Panageas K,Kryza-Lacombe M,Buthorn J,Neil EC,Miller AM,DeAngelis LM,Applebaum AJ

    更新日期:2017-10-19 00:00:00

  • Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study.

    abstract:BACKGROUND:The colony stimulating factor 1 receptor (CSF1R) ligands, CSF1 and interleukin-34, and the KIT ligand, stem cell factor, are expressed in glioblastoma (GB). Microglia, macrophages, blood vessels, and tumor cells also express CSF1R, and depletion of the microglia reduces tumor burden and invasive capacity. PL...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1093/neuonc/nov245

    authors: Butowski N,Colman H,De Groot JF,Omuro AM,Nayak L,Wen PY,Cloughesy TF,Marimuthu A,Haidar S,Perry A,Huse J,Phillips J,West BL,Nolop KB,Hsu HH,Ligon KL,Molinaro AM,Prados M

    更新日期:2016-04-01 00:00:00

  • Akt2 and Akt3 play a pivotal role in malignant gliomas.

    abstract::Akt, one of the major downstream effectors of phosphatidylinositol 3-kinase, is hyper-expressed and activated in a variety of cancers including glioblastoma. However, the expression profiles of the Akt isoforms Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma and their functional roles in malignant glioma are not well u...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nop026

    authors: Mure H,Matsuzaki K,Kitazato KT,Mizobuchi Y,Kuwayama K,Kageji T,Nagahiro S

    更新日期:2010-03-01 00:00:00

  • ELK4 neutralization sensitizes glioblastoma to apoptosis through downregulation of the anti-apoptotic protein Mcl-1.

    abstract::Glioma is the most common adult primary brain tumor. Its most malignant form, glioblastoma multiforme (GBM), is almost invariably fatal, due in part to the intrinsic resistance of GBM to radiation- and chemotherapy-induced apoptosis. We analyzed B-cell leukemia-2 (Bcl-2) anti-apoptotic proteins in GBM and found myeloi...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor119

    authors: Day BW,Stringer BW,Spanevello MD,Charmsaz S,Jamieson PR,Ensbey KS,Carter JC,Cox JM,Ellis VJ,Brown CL,Walker DG,Inglis PL,Allan S,Reynolds BA,Lickliter JD,Boyd AW

    更新日期:2011-11-01 00:00:00

  • The molecular profile of microglia under the influence of glioma.

    abstract::Microglia, which contribute substantially to the tumor mass of glioblastoma, have been shown to play an important role in glioma growth and invasion. While a large number of experimental studies on functional attributes of microglia in glioma provide evidence for their tumor-supporting roles, there also exist hints in...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/nos116

    authors: Li W,Graeber MB

    更新日期:2012-08-01 00:00:00