Protein kinase B modulates the sensitivity of human neuroblastoma cells to insulin-like growth factor receptor inhibition.


:The potential of the novel insulin-like growth factor receptor (IGF-IR) inhibitor NVP-AEW541 as an antiproliferative agent in human neuroblastoma was investigated. Proliferation of a panel of neuroblastoma cell lines was inhibited by NVP-AEW541 with IC(50) values ranging from 0.15 to 5 microM. Experiments using an IGF-IR neutralizing antibody confirmed that the IGF-IR was essential to support growth of neuroblastoma cell lines. The expression levels of the IGF-IR in individual neuroblastoma cell lines did not correlate with the sensitivities to NVP-AEW541, while coexpression of the IGF-IR and the insulin receptor (IR) correlated with lower sensitivity to the inhibitor in some cell lines. Intriguingly, high levels of activation of Akt/protein kinase B (PKB) and phosphorylation of the ribosomal S6 protein were observed in neuroblastoma cell lines with decreased sensitivities to NVP-AEW541. Inhibition of Akt/PKB activity restored the sensitivity of neuroblastoma cells to the IGF-IR inhibitor. Transfection of neuroblastoma cells with activated Akt or ribosomal protein S6 kinase (S6K) decreased the sensitivity of the cells to NVP-AEW541. IGF-I-stimulated proliferation of neuroblastoma cell lines was completely blocked by NVP-AEW541, or by a combination of an inhibitor of phosphoinositide 3-kinase and rapamycin. In addition to its antiproliferative effects, NVP-AEW541 sensitized neuroblastoma cells to cisplatin-induced apoptosis. Together, our data demonstrate that NVP-AEW541 in combination with Akt/PKB inhibitors or chemotherapeutic agents may represent a novel approach to target human neuroblastoma cell proliferation.


Int J Cancer


Guerreiro AS,Boller D,Shalaby T,Grotzer MA,Arcaro A




Has Abstract


2006-12-01 00:00:00












  • Losses of the tumor suppressor BIN1 in breast carcinoma are frequent and reflect deficits in programmed cell death capacity.

    abstract::Oncogenic activation of MYC occurs often in breast carcinoma and is associated with poor prognosis. Loss or inactivation of mechanisms that restrain MYC may therefore be involved in tumor progression. In this study, we show that the MYC-interacting adaptor protein BIN1 is frequently missing in malignant breast cells a...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Ge K,Duhadaway J,Sakamuro D,Wechsler-Reya R,Reynolds C,Prendergast GC

    更新日期:2000-02-01 00:00:00

  • The prognostic significance of two epithelial membrane antigens expressed by human mammary carcinomas.

    abstract::As many patients with mammary carcinoma are now treated by conservative forms of surgery, there is a need for prognostic information obtainable from the primary tumour alone. One possible source is the antigenic profile of tumour cells. Using an indirect immunoperoxidase technique, we stained histological sections of ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Wilkinson MJ,Howell A,Harris M,Taylor-Papadimitriou J,Swindell R,Sellwood RA

    更新日期:1984-03-15 00:00:00

  • An estimate of the proportion of colo-rectal and stomach cancers which might be prevented by certain changes in dietary habits.

    abstract::The colo-rectum and stomach are the 2 sites for which the role of diet in the etiology of cancer is most heavily implicated. Quantitative estimates as to the proportion of cancer deaths attributable to diet vary considerably. This may be partially due to the application of the concept of population attributable risk w...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Wahrendorf J

    更新日期:1987-11-15 00:00:00

  • A case-control study of diet and gastric cancer in northern Italy.

    abstract::Dietary factors in the aetiology of stomach cancer were investigated using data from a case-control study conducted in Northern Italy on 206 histologically confirmed carcinomas and 474 control subjects in hospital for acute, non-digestive conditions, unrelated to any of the potential risk factors for gastric cancer. D...

    journal_title:International journal of cancer

    pub_type: 杂志文章


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    更新日期:1987-10-15 00:00:00

  • Two distinct regions of deletion on chromosome 13q in primary nasopharyngeal carcinoma.

    abstract::Nasopharyngeal carcinoma (NPC) is rare in most parts of the world, but prevalent in Southern China. Although this disease poses a serious health problem in our population, the genetic alterations that lead to the development of NPC have yet to be defined. In a comparative genomic hybridization (CGH) study on NPC by ou...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Tsang YS,Lo KW,Leung SF,Choi PH,Fong Y,Lee JC,Huang DP

    更新日期:1999-10-29 00:00:00

  • Embryo-derived teratocarcinoma. IV. The role of immune factors in the regulation of teratocarcinogenesis.

    abstract::Seven-day-old mouse embryos were transplanted under the kidney capsule of adult syngeneic recipients which were either X-irradiated, treated with cyclophosphamide, splenectomized or immunized with teratocarcinoma cell lines prior to embryonic transplantation. The yield of malignant tumors was decreased in preirradiate...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Damjanov I,Bagasra O,Dominis M,Solter D

    更新日期:1982-12-15 00:00:00

  • Binding of a SART3 tumor-rejection antigen to a pre-mRNA splicing factor RNPS1: a possible regulation of splicing by a complex formation.

    abstract::We recently reported the identification of a human SART3 gene that encodes a tumor-rejection antigen recognized by cytotoxic T lymphocytes (CTLs). The squamous-cell carcinoma antigen recognized by T cells-3 (SART3) is an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including nor...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Harada K,Yamada A,Yang D,Itoh K,Shichijo S

    更新日期:2001-09-01 00:00:00

  • Elucidating the molecular basis of MSH2-deficient tumors by combined germline and somatic analysis.

    abstract::In a proportion of patients presenting mismatch repair (MMR)-deficient tumors, no germline MMR mutations are identified, the so-called Lynch-like syndrome (LLS). Recently, MMR-deficient tumors have been associated with germline mutations in POLE and MUTYH or double somatic MMR events. Our aim was to elucidate the mole...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Vargas-Parra GM,González-Acosta M,Thompson BA,Gómez C,Fernández A,Dámaso E,Pons T,Morak M,Del Valle J,Iglesias S,Velasco À,Solanes A,Sanjuan X,Padilla N,de la Cruz X,Valencia A,Holinski-Feder E,Brunet J,Feliubadaló L

    更新日期:2017-10-01 00:00:00

  • Claudin7-dependent exosome-promoted reprogramming of nonmetastasizing tumor cells.

    abstract::Claudin7 (cld7) is a cancer-initiating cell (CIC) marker in gastrointestinal tumors, a cld7-knockdown (kd) being accompanied by loss of tumor progression. Tumor exosomes (TEX) restoring CIC activities, we explored the contribution of cld7. This became particularly interesting, as tight junction (TJ)- and glycolipid-en...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Kyuno D,Zhao K,Schnölzer M,Provaznik J,Hackert T,Zöller M

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  • Growth-factor-dependent migration of human lung-cancer cells.

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    journal_title:International journal of cancer

    pub_type: 杂志文章


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  • Therapeutic anti-tumor response induced with epitope-pulsed fibroblasts genetically engineered for B7.1 expression and IFN-gamma secretion.

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    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Kim TS,Chung SW,Kim SH,Kang SN,Kang BY

    更新日期:2000-08-01 00:00:00

  • Prospective study on the role of glucose metabolism in breast cancer occurrence.

    abstract::High circulating glucose, insulin resistance and obesity appear to be associated with increased risk of breast cancer (BC). We sought further insight into the relation of these variables to BC. We assessed associations of BC risk with serum fasting glucose, insulin, homeostasis model assessment-insulin resistance (HOM...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Sieri S,Muti P,Claudia A,Berrino F,Pala V,Grioni S,Abagnato CA,Blandino G,Contiero P,Schunemann HJ,Krogh V

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  • Hypermethylation of the tumor suppressor gene RASSFIA and frequent concomitant loss of heterozygosity at 3p21 in cervical cancers.

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    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Yu MY,Tong JH,Chan PK,Lee TL,Chan MW,Chan AW,Lo KW,To KF

    更新日期:2003-06-10 00:00:00

  • Interaction of human immunodeficiency and papilloma viruses: association with anal epithelial abnormality in homosexual men.

    abstract::During the 7th annual follow-up of our cohort of homosexual men in 1989, we tested the hypotheses that infection with human immunodeficiency virus (HIV) may enhance the expression of human papilloma virus (HPV) and that the development of anal epithelial abnormality is related to a biologic interaction between these t...

    journal_title:International journal of cancer

    pub_type: 杂志文章


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  • A functional TNFRSF5 polymorphism and risk of non-Hodgkin lymphoma, a pooled analysis.

    abstract::Interaction between CD40 and its ligand, CD154, has a key function in immune regulation. Recent experimental data support a role of deregulated CD40 signalling in lymphomagenesis. Data from earlier studies that are part of this pooling study implicate a functional polymorphism (-1C>T, rs1883832) in the TNFRSF5 gene en...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Nieters A,Bracci PM,de Sanjosé S,Becker N,Maynadié M,Benavente Y,Foretova L,Cocco P,Staines A,Holly EA,Boffetta P,Brennan P,Skibola CF

    更新日期:2011-03-15 00:00:00

  • Prophylactic effect of pemirolast, an antiallergic agent, against hypersensitivity reactions to paclitaxel in patients with ovarian cancer.

    abstract::We have previously shown that sensory nerve peptides contribute to the pathogenesis of pulmonary hypersensitivity reactions (HSRs) to paclitaxel in rats. Moreover, pemirolast, an antiallergic agent, reverses the HSRs to paclitaxel, although the mechanism is considered to result from the blockade of paclitaxel-induced ...

    journal_title:International journal of cancer

    pub_type: 杂志文章,随机对照试验


    authors: Yahata H,Saito M,Sendo T,Itoh Y,Uchida M,Hirakawa T,Nakano H,Oishi R

    更新日期:2006-05-15 00:00:00

  • HPV-associated flat penile lesions in men of a non-STD hospital population: less frequent and smaller in size than in male sexual partners of women with CIN.

    abstract::Human papillomavirus (HPV) infections and HPV-associated penile lesions are frequently found in male sexual partners of women with cervical intraepithelial neoplasia (CIN). To determine the significance of these findings, we studied the prevalence of HPV and HPV associated penile lesions in a male hospital population ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Bleeker MC,Hogewoning CJ,Voorhorst FJ,van den Brule AJ,Berkhof J,Hesselink AT,Lettink M,Starink TM,Stoof TJ,Snijders PJ,Meijer CJ

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  • Endometriosis as a prognostic factor for cancer survival.

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    journal_title:International journal of cancer

    pub_type: 杂志文章,随机对照试验


    authors: Melin A,Lundholm C,Malki N,Swahn ML,Sparen P,Bergqvist A

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  • Reverse transcription-polymerase chain reaction assay for multiple mRNA markers in the detection of breast cancer metastases in sentinel lymph nodes.

    abstract::The identification of specific tumor mRNA markers by reverse transcription-polymerase chain reaction might be a valuable diagnostic adjunct for the detection of breast cancer metastases in axillary sentinel lymph nodes (SLNs). In this study we have compared the diagnostic accuracy of an extensive histopathologic exami...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Manzotti M,Dell'Orto P,Maisonneuve P,Zurrida S,Mazzarol G,Viale G

    更新日期:2001-09-20 00:00:00

  • Cytolytic activity against tumor cells by macrophage cell lines and augmentation by macrophage stimulants.

    abstract::Previous studies have shown that macrophage cell lines retained the ability to phagocytize, to secrete lysosomal enzymes, and to function as effector cells in antibody-dependent cellular cytoxicity. In this paper, the cytolytic activity of murine macrophage cell lines against tumor target cells was assessed using an 1...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Taniyama T,Holden HT

    更新日期:1980-07-15 00:00:00

  • Inhibition of nuclear factor kappab activity by genistein is mediated via Notch-1 signaling pathway in pancreatic cancer cells.

    abstract::Pancreatic cancer remains the fourth most common cause of cancer related death in the United States. Therefore, novel strategies for the prevention and treatment are urgently needed. Genistein is a prominent isoflavonoid found in soy products and has been proposed to be responsible for lowering the rate of pancreatic ...

    journal_title:International journal of cancer

    pub_type: 杂志文章,收录出版


    authors: Wang Z,Zhang Y,Banerjee S,Li Y,Sarkar FH

    更新日期:2006-04-15 00:00:00

  • In vivo pH in metabolic-defective Ras-transformed fibroblast tumors: key role of the monocarboxylate transporter, MCT4, for inducing an alkaline intracellular pH.

    abstract::We present an investigation of tumor pH regulation, designed to support a new anticancer therapy concept that we had previously proposed. Our study uses a tumor model of ras-transformed hamster fibroblasts, CCL39, xenografted in the thighs of nude mice. We demonstrate, for the first time, that genetic modifications of...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Chiche J,Le Fur Y,Vilmen C,Frassineti F,Daniel L,Halestrap AP,Cozzone PJ,Pouysségur J,Lutz NW

    更新日期:2012-04-01 00:00:00

  • Identification of Hodgkin and Sternberg-reed cells as a unique cell type derived from a newly-detected small-cell population.

    abstract::In this study the antigenic profile of Hodgkin (H) and Sternberg-Reed (SR) cells from cases of Hodgkin's disease was analysed using a large panel of monoclonal and polyclonal antibodies reactive with cells of lymphoid and haemotopoietic origin. The aim of this investigation was, firstly, to throw light on the origin o...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Stein H,Gerdes J,Schwab U,Lemke H,Mason DY,Ziegler A,Schienle W,Diehl V

    更新日期:1982-10-15 00:00:00

  • Transient depletion of CD4(+) T cells augments IL-21-based immunotherapy of disseminated neuroblastoma in syngeneic mice.

    abstract::IL-21 is a member of the IL-2 cytokine family, produced by CD4+ T cells. We previously showed that immunotherapy (IT) with IL-21-transduced neuroblastoma cells (Neuro2a/IL-21) cured 33% of syngeneic mice bearing systemic NB. Here, we studied whether the removal of Treg cells could potentiate the therapeutic efficacy o...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Croce M,Corrias MV,Orengo AM,Brizzolara A,Carlini B,Borghi M,Rigo V,Pistoia V,Ferrini S

    更新日期:2010-09-01 00:00:00

  • Telomerase components as a diagnostic tool in human oral lesions.

    abstract::Telomerase activity is considered to be a diagnostic marker of malignancy since most malignant cells express this activity and most somatic cells do not. However, the detection of telomerase activity is rather complicated and is affected by many factors. Recently, human telomerase components were cloned and found to c...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Sumida T,Hamakawa H,Sogawa K,Sugita A,Tanioka H,Ueda N

    更新日期:1999-01-05 00:00:00

  • Screening for familial and hereditary prostate cancer.

    abstract::Prostate cancer (PC) has the highest degree of genetic transmission of any form of malignancy. In some families, the hereditary pattern is so strong as to mimic an autosomal dominance trait. We reviewed the known predisposing genetic markers to assess possible strategies for screening of families at risk. We carried o...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审


    authors: Lynch HT,Kosoko-Lasaki O,Leslie SW,Rendell M,Shaw T,Snyder C,D'Amico AV,Buxbaum S,Isaacs WB,Loeb S,Moul JW,Powell I

    更新日期:2016-06-01 00:00:00

  • Expression of membrane type 1 matrix metalloproteinase (MT1-MMP) in A2058 melanoma cells is associated with MMP-2 activation and increased tumor growth and vascularization.

    abstract::Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase overexpressed in tumors, which plays a major role in the first step of pro-MMP-2 activation, leading to the generation of an intermediate 62 kDa species. The second step of MMP-2 activation that yields to the mature form is less understoo...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Sounni NE,Baramova EN,Munaut C,Maquoi E,Frankenne F,Foidart JM,Noël A

    更新日期:2002-03-01 00:00:00

  • Smoking, snus use and risk of right- and left-sided colon, rectal and anal cancer: a 37-year follow-up study.

    abstract::Although some authorities consider smoking to be an established risk factor for colorectal cancer, the international literature is not entirely consistent. Further, only 1 study has addressed the association with smokeless tobacco and none with Scandinavian moist snuff (snus). This retrospective cohort study included ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Nordenvall C,Nilsson PJ,Ye W,Nyrén O

    更新日期:2011-01-01 00:00:00

  • NK and CD8+ T cell-mediated eradication of poorly immunogenic B16-F10 melanoma by the combined action of IL-12 gene therapy and 4-1BB costimulation.

    abstract::In previous reports, systemic administration of a stimulatory monoclonal antibody directed against the 4-1BB receptor had no effect on survival or tumor burden in mice inoculated with the poorly immunogenic B16-F10 melanoma. We combined IL-12 gene transfer with 4-1BB costimulation to explore a previously noted coopera...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Xu D,Gu P,Pan PY,Li Q,Sato AI,Chen SH

    更新日期:2004-04-20 00:00:00

  • Rapamycin inhibits proliferation of human neuroblastoma cells without suppression of MycN.

    abstract::MYCN and insulin-like growth factor (IGF) system are important for the pathogenesis and development of neuroblastoma. We previously reported evidence of a direct linkage between MycN and the IGF system in KP-N-RT human neuroblastoma cells, where IGF-I induced both MycN expression at the RNA level and G1-S cell cycle p...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Misawa A,Hosoi H,Tsuchiya K,Sugimoto T

    更新日期:2003-03-20 00:00:00