28 Synergistic antiproliferative effects of ionizing radiations with anti-epidermal growth factor receptor monoclonal antibody C225 and protein kinase a antisense oligonucleotide hyb 165

Bianco, Cataldo; Ciardiello, F.; Montemaggi, Paolo; Guerrieri, Patrizia; Mendelsohn, J.; Agrawal, S.

doi:10.1016/s0360-3016(99)90046-9

Cited by 37 publications

(54 citation statements)

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“…Note that these cells were not pretreated with EGF or any other NFκB activator. A549, OVCAR3, H1048, and SW1271 cells have wild-type EGFR (27)(28)(29)(30), whereas HCC827 cells carry an activating EGFR mutation (31). As expected, erlotinib inhibits EGFR phosphorylation in all of these cells and, importantly, it also decreases greatly the phosphorylation of IκB, within 2-3 h (Fig.…”

Section: Egfr Mediates Nfκb Activation In Several Cancer Cell Linessupporting

confidence: 70%

EGF receptor uses SOS1 to drive constitutive activation of NFκB in cancer cells

Dermawan

Stark

2014

Proc. Natl. Acad. Sci. U.S.A.

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Activation of nuclear factor κB (NFκB) is a central event in the responses of normal cells to inflammatory signals, and the abnormal constitutive activation of NFκB is important for the survival of most cancer cells. In nonmalignant human cells, EGF stimulates robust activation of NFκB. The kinase activity of the EGF receptor (EGFR) is required, because the potent and specific inhibitor erlotinib blocks the response. Down-regulating EGFR expression or inhibiting EGFR with erlotinib impairs constitutive NFκB activation in several different types of cancer cells and, conversely, increased activation of NFκB leads to erlotinib resistance in these cells. We conclude that EGF is an important mediator of NFκB activation in cancer cells. To explore the mechanism, we selected an erlotinibresistant cell line in which the guanine nucleotide exchange factor Son of Sevenless 1 (SOS1), well known to be important for EGFdependent signaling to MAP kinases, is overexpressed. Increased expression of SOS1 increases NFκB activation in several different types of cancer cells, and ablation of SOS1 inhibits EGF-induced NFκB activation in these cells, indicating that SOS1 is a functional component of the pathway connecting EGFR to NFκB activation. Importantly, the guanine nucleotide exchange activity of SOS1 is not required for NFκB activation.

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Section: Egfr Mediates Nfκb Activation In Several Cancer Cell Linessupporting

confidence: 70%

EGF receptor uses SOS1 to drive constitutive activation of NFκB in cancer cells

Dermawan

Stark

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…EGFR is stimulated by a number of autocrine growth factors, including EGF and TGFa. Recently, it has been shown that ionising radiation stimulates EGFR activation and cellular proliferation (Schmidt-Ullrich et al, 1997; Dent et al, 1999;Reardon et al, 1999;Todd et al, 1999) and that anti-EGFR antibody approaches can improve tumour radiation response (Saleh et al, 1999;Bianco et al, 2000;Milas et al, 2000). In the present study, we evaluated the potential influence of ZD1839 on the radiation response of the human colorectal carcinoma cell line LoVo which has moderate levels of EGFR expression (33 000 receptors per cell), and is therefore likely to be representative of most epithelial tumour cell lines (Caraglia et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

ZD1839 (‘Iressa’), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model

et al. 2002

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The effect of ZD1839 (‘Iressa’), a specific inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor, on the radiation response of human tumour cells (LoVo colorectal carcinoma) was evaluated in vitro and in vivo . ZD1839 (0.5 μ M , incubated days 1–5) significantly increased the anti-proliferative effect of fractionated radiation treatment (2 Gy day −1 , days 1–3) on LoVo cells grown in vitro ( P =0.002). ZD1839 combined with either single or fractionated radiotherapy in mice bearing LoVo tumour xenografts, also produced a highly significant increase in tumour growth inhibition ( P ⩽0.001) when compared to treatment with either modality alone. The radio-potentiating effect of ZD1839 was more apparent when radiation was administered in a fractionated protocol. This phenomenon may be attributed to an anti proliferative effect of ZD1839 on tumour cell re-population between radiotherapy fractions. These data suggest radiotherapy with adjuvant ZD1839 could enhance treatment response. Clinical investigation of ZD1839 in combination with radiotherapy is therefore warranted. British Journal of Cancer (2002) 86 , 1157–1161. DOI: 10.1038/sj/bjc/6600182 www.bjcancer.com © 2002 Cancer Research UK

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“…There are numerous experimental data both in vitro and in vivo showing that EGFR targeting is able to augment the antitumour activity of several anticancer agents including doxorubicin, cisplatin, 5-fluorouracil (5FU), gemcitabine, paclitaxel and topotecan Fan et al, 1993;Ciardiello et al, 1999;Bruns et al, 2000;Inoue et al, 2000;Overholser et al, 2000). Similar enhancement of activity has also been observed in studies combining EGFR-targeting agents, particularly the monoclonal antibody IMC C225 (cetuximab), with ionizing radiation (Huang et al, 1999;Saleh et al, 1999;Bianco et al, 2000;Bonner et al, 2000;Milas et al, 2000). Other investigators (Williams et al, 2002) and this laboratory (Magné et al, 2002a) recently showed supra-additive effects between irradiation and ZD1839, confirming the radiosensitisation conferred by an EGFRtargeting agent.…”

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confidence: 82%

Molecular mechanisms underlying the interaction between ZD1839 (‘Iressa’) and cisplatin/5-fluorouracil

et al. 2003

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ZD1839 ('Iressa'), an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is currently being investigated in clinical trials as a treatment for cancer. 'Iressa' is a trademark of the AstraZeneca group of companies. We have previously demonstrated a synergistic interaction between ZD1839 and cisplatin/5-fluorouracil (5FU) in CAL33, a human head and neck cancer cell line that markedly expresses EGFR. This study examined the effects of this drug combination on the cell cycle, cell cycle regulators, apoptosis-related factors, EGFR-related signalling and DNA repair in CAL33 cells. The cells were incubated with ZD1839 alone for 48 h, then cisplatin and 5FU were added. Exposure to the drug combination continued for a further 48 h. ZD1839 alone induced accumulation of cells in the G0/G1 phase of the cell cycle at 24 h accompanied by a concomitant increase in p21, p27 and Bax, a significant decrease in Bcl2 and a decrease in Akt phosphorylation. A decrease in DNA-PK was observed at 48 h. ZD1839 alone had no effect on caspase-3 activity, but addition of ZD1839 to cisplatin-5FU led to a significant increase in caspase-3 activity at 96 h. Thus, ZD1839 affects key cellular pathways controlling cell proliferation, apoptosis and DNA repair. These data provide a rationale to support clinical trials combining ZD1839 and cisplatin -5FU and other protocols that combine EGFR-targeting agents with chemotherapy or radiotherapy.

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28 Synergistic antiproliferative effects of ionizing radiations with anti-epidermal growth factor receptor monoclonal antibody C225 and protein kinase a antisense oligonucleotide hyb 165

Cited by 37 publications

References 0 publications

EGF receptor uses SOS1 to drive constitutive activation of NFκB in cancer cells

EGF receptor uses SOS1 to drive constitutive activation of NFκB in cancer cells

ZD1839 (‘Iressa’), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model

Molecular mechanisms underlying the interaction between ZD1839 (‘Iressa’) and cisplatin/5-fluorouracil

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