Abstract:
:Mechanisms leading to inhibitory effects of an anti-GD2 ganglioside (GD2) 14G2a mouse monoclonal antibody (mAb) and PI3K/Akt/mTOR pathway inhibitors on human neuroblastoma cell survival were studied in vitro. We have recently shown on IMR-32, CHP‑134, and LA-N-1 neuroblastoma cells that targeting GD2 with the mAb decreases cell viability of the cell lines. In this study we used cytotoxicity assays, proteomic arrays and immunoblotting to evaluate the response of the three cell lines to the anti‑GD2 14G2a mAb and specific PI3K/Akt/mTOR pathway inhibitors. We show here that the mAb modulates intracellular signal transduction through changes in several kinases and their substrates phosphorylation. More detailed analysis of the PI3K/Akt/mTOR pathway showed significant decrease in activity of Akt, mTOR, p70 S6 and 4E-BP1 proteins and transient increase in PTEN (a suppressor of the pathway), leading to inhibition of the signaling network responsible for stimulation of translation and proliferation. Additionally, combining the GD2-specific 14G2a mAb with an Akt inhibitor (perifosine), dual mTOR/PI3K inhibitors (BEZ-235 and SAR245409), and a pan-PI3K inhibitor (LY294002) was shown to enhance cytotoxic effects against IMR-32, CHP‑134 and LA-N-1 cells. Our study extends knowledge on mechanisms of action of the 14G2a mAb on the neuroblastoma cells. Also, it stresses the need for further delineation of molecular signal orchestration aimed at more reasonable selection of drugs to target key cellular pathways in quest for better cure for neuroblastoma patients.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Durbas M,Horwacik I,Boratyn E,Kamycka E,Rokita Hdoi
10.3892/ijo.2015.3070subject
Has Abstractpub_date
2015-09-01 00:00:00pages
1143-59issue
3eissn
1019-6439issn
1791-2423journal_volume
47pub_type
杂志文章abstract::The purpose of this study was to test the hypothesis that cooperative interaction between cutaneous fatty acid-binding protein (C-FABP) and peroxisome proliferator-activated receptors (PPAR) promotes the malignant progression of human prostate cancer. The expression of C-FABP, PPARβ/δ and PPARγ was measured by western...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2166
更新日期:2014-01-01 00:00:00
abstract::The expression of proinflammatory cytokines in various malignant neoplasms is widely considered to represent the host immune response to tumor development. The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of o...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4590
更新日期:2018-12-01 00:00:00
abstract::Dendritic cells (DCs) are powerful antigen-presenting cells (APCs), that have so far been applied for cancer specific immunotherapy. Recent results suggest that matured DCs derived from human monocytes have a significant impact on the outcome of vaccination. The conventional generation of mature DCs from human monocyt...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
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abstract::Nanoparticles are promising novel drug delivery carriers that allow tumor targeting and controlled drug release. In the present study, we prepared poly butyl-cyanoacrylate nanoparticles (PBCA-NP) entrapped with hypocrellin B (HB) to improve the effect of photodynamic therapy (PDT) in ovarian cancer. An ovarian cancer ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.3079
更新日期:2015-09-01 00:00:00
abstract::Cancer progression has been associated with an increase in genomic instability indicated by inactivation of tumor suppressor genes and activation of oncogenes. Epidemiological and experimental evidence has implicated estrogens in the etiology of breast cancer. To study environmental organophosphorous pesticides is of ...
journal_title:International journal of oncology
pub_type: 杂志文章
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.12.5.1137
更新日期:1998-05-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3510
更新日期:2016-07-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-05-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章,已发布勘误
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更新日期:2019-05-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.10.3.539
更新日期:1997-03-01 00:00:00
abstract::Telomerase (T) is a ribonucleoprotein complex that includes the telomerase RNA component (hTR), telomerase associated protein (TP1) and the telomerase catalytic subunit (hTERT). Telomerase has been shown in stem cells and found to be activated in tumor tissues and immortalized cells. We wanted to test whether the expr...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:
更新日期:2002-08-01 00:00:00
abstract::Elevated levels of p21WAF1/CIP1, an important mediator of DNA repair, have been observed in various aggressive tumors as well as linked to chemoresistance. We examined whether heregulin (HRG), a member of the EGF-like growth factor family closely related to breast cancer tumorigenesis and metastasis, modulates p21WAF1...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2005-03-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1224
更新日期:2012-01-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2331
更新日期:2014-05-01 00:00:00
abstract::A monoclonal antibody (MSN-3) was raised using HEC-108 cells derived from poorly differentiated endometrial carcinoma as the immunogen. The immunoglobulin subclass of MSN-3 was IgGr1. The target antigen of MSN-3 was a protein with a molecular weight of 77 kDa, and it was shown to be localized in the cytoplasm. MSN-3 o...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.11.4.749
更新日期:1997-10-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000545
更新日期:2010-03-01 00:00:00
abstract::This review focuses on two chemotherapeutic agents belonging to the family of purine analogs, 9-beta-D-arabinosyl-2-fluoroadenine-5'-monophosphate (F-ara-AMP, fludarabine), which is the soluble form of F-ara-A, and 2-chloro-2'-deoxyadenosine (CdA, cladribine). Both compounds display remarkable activity in malignancies...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:
更新日期:2005-10-01 00:00:00
abstract::We have previously reported that Insulin-like growth factor (IGF-I) is a cellular growth factor of human transformed T-lymphocytes. To evaluate the role of IGF-I for nontransformed T-cells we investigated synthesis of IGF-I and the influence of an IGF-I antiserum, UBK487, during proliferation process. IGF-I is synthes...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2.6.1003
更新日期:1993-06-01 00:00:00
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journal_title:International journal of oncology
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更新日期:2016-04-01 00:00:00
abstract::Although HIF-1α is considered an attractive target for the development of cancer therapies, like other transcriptional factors, it has been regarded as 'undruggable'. The decoy approach is a new class of antigene strategy that can be used to modulate the function of endogenous transcriptional factors. Here, we designe...
journal_title:International journal of oncology
pub_type: 杂志文章
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journal_title:International journal of oncology
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更新日期:2018-01-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2539
更新日期:2014-10-01 00:00:00
abstract::The Tap1 and Tap2 genes encoding for a heterodimeric peptide transporter play a key role in antigen processing and presentation. The TAP complex mediates the transport of peptides generated by the IFN-gamma-inducible proteasome subunits LMP2, 7 and 10 from the cytosol into the endoplasmic reticulum (ER), where they bi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
abstract::Cytokines of the TGF beta family are thought to be involved in cellular growth control and are therefore likely candidates to regulate homeostasis of the prostate. We have analyzed immunohistochemically the expression of TGF-beta 3 in normal prostate (NP), benign prostate hyperplasia (BPH) and prostate cancer (PCa). I...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.11.6.1185
更新日期:1997-12-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1278
更新日期:2012-04-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2761
更新日期:2015-02-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1196
更新日期:2012-01-01 00:00:00
abstract::The relation between the consumption of cruciferous vegetables and reduced prostate cancer occurrence has been documented, although the responsible phytochemicals are unknown. The effects of sulforaphane (SFN) which occurs as the precursor glucosinolate in broccoli and other cruciferous vegetables, and its metabolite ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.20.3.631
更新日期:2002-03-01 00:00:00
abstract::Inflammatory abnormalities have been implicated in the pathogenesis of various human diseases, including cancer. Interleukin-1 receptor antagonist (IL1RN) is a potent anti-inflammatory molecule that modulates the biological activity of the proinflammatory cytokine, interleukin-1. The aim of this study was to examine t...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2917
更新日期:2015-05-01 00:00:00