True

Abstract

The receptor for epidermal growth factor (EGF) is a transmembrane glycoprotein with intrinsic tyrosine kinase activity (Ullrich and Schlessinger, 1990). Many human cancers of epithelial origin express high numbers of EGF receptors and are stimulated by activation of the receptor via a transforming growth factor-α (TGF-α)/EGF receptor autocrine loop (Ozanne et al, 1986;Cowley et al, 1986;Ishitoya et al, 1989;Hendler and Ozanne, 1984). The increased receptor levels are associated with poor clinical prognosis in patients with cancers of the bladder (Neal et al, 1985), breast , and lung (Veale et al, 1987) and others. Blockade of EGF receptor as an approach for anticancer therapy has been extensively studied over the past decade (Fan and Mendelsohn, 1998).Monoclonal antibody (mAb) 225 binds to EGF receptor with an affinity similar to that of the natural ligands EGF and TGF-α, competes with these natural ligands for receptor binding, and inhibits ligand-induced activation of the receptor tyrosine kinase (Sato et al, 1983;Gill et al, 1984). This antibody, along with other EGF receptor-blocking mAbs, inhibits the proliferation of a variety of cultured and xenografted tumour cell lines that are stimulated by the TGF-α/EGF receptor autocrine loop, including cell lines derived from cancers of the vulva (Fan et al, 1993a;1994), breast (Ennis et al, 1989), prostate (Peng et al, 1996;Hofer et al, 1991), ovary (Ye et al, 1999), bladder (Perrotte et al, 1999), kidney (Prewett et al, 1998), lung (Lee et al, 1992), colon (Karnes et al, 1992;Wu et al, 1996), brain (Wersall et al, 1997), and head and neck (Modjtahedi et al, 1993). It has been postulated that these antibodies inhibit tumour cell proliferation by an antibody-mediated interruption of the autocrine activation of EGF receptors in cancer cells (Van de Vijver et al, 1991;Fan et al, 1993b;Baselga et al, 1996). The antibody-mediated growth inhibition in most malignant cell lines has been attributed primarily to a reduced proliferation rate with an increased cell population in G1 phase of the cell cycle (Fan et al, 1997;Wu et al, 1996;Peng et al, 1996). In nonmalignant epithelial cells there was a prominent cytostatic effect with complete G1 arrest (Stampfer et al, 1993;Chou et al, 1999).DiFi colon cancer cells are unique in that exposure of these cells to mAb 225 resulted in not only G1 phase arrest of cell cycle, with a concomitant increase in the level of p27 Kip1 and a decrease in CDK activity, but also subsequent cell death through apoptosis (Wu et al, 1995;. When nude mice bearing well-established subcutaneous DiFi cell xenografts were treated with mAb 225, the tumour was completely eradicated, a result not normally seen with other cancer cells stimulated by the TGF-α/EGF receptor autocrine pathway (Masui et al, 1991). The EGF receptor gene in these cells was not found to be rearranged or genetically altered, but the gene was found to be amplified in the range of 60-80 copies per cell, which is approximately twice the copy number SummaryWe previously reported that e...

1, 9-Pyrazoloanthrones Downregulate HIF-1α and Sensitize Cancer Cells to Cetuximab-Mediated Anti-EGFR Therapy

“…We measured apoptosis using an enzyme-linked immunosorbent assay (ELISA) kit (Roche Diagnostics Corp., Indianapolis, IN) that quantitatively measures cytoplasmic histone-associated DNA fragments (mononucleosomes and oligonucleosomes) and by Western blotting with an antibody that recognizes both uncleaved and cleaved PARP after various treatments, as previously described [43] , [44] .…”

The Latest Battles Between EGFR Monoclonal Antibodies and Resistant Tumor Cells

“…Tumor cells with high expression of EGFR are often accompanied by a significant increase in the level of pro-angiogenic factors, resulting in increased angiogenesis. Cetuximab can significantly inhibit the expression of pro-angiogenic factors, thereby reducing tumor angiogenesis ( 21 – 23 ); (f). Cetuximab or other similar anti-EGFR antibody treatments alter Bcl-2 (anti-apoptosis) and Bax (pro-apoptosis) protein balance, promoting apoptosis in tumor cells ( 23 , 24 ); (g).…”

“…Cetuximab can significantly inhibit the expression of pro-angiogenic factors, thereby reducing tumor angiogenesis ( 21 – 23 ); (f). Cetuximab or other similar anti-EGFR antibody treatments alter Bcl-2 (anti-apoptosis) and Bax (pro-apoptosis) protein balance, promoting apoptosis in tumor cells ( 23 , 24 ); (g). In a recent study, cetuximab was shown to induce radiosensitization of A549 cells by increasing H2AX (H2A histone family, member X) levels and inhibiting DNA-pk ( 25 ).…”

The potential effect of Schisandrin‐B combination with panitumumab in wild‐type and mutant colorectal cancer cell lines: Role of apoptosis and autophagy

“…Our results are in line with a former study which reported that cetuximab induced DNA fragmentation and caspase-3 activation in WT colon cancer cells. [33] In addition, apoptotic cell death was not detected in HCT-116 or HT-29 cell lines treated with panitumumab or cetuximab as mono-treatments. [34] As previously reported, anti-EGFR inhibitors reduce the phosphorylated level of Akt [35] and increase the level of cleaved caspase-3, inducing apoptotic cell death.…”