Radiosensitization by Pan ErbB Inhibitor CI-1033 
 in Vitro
 and 
 in Vivo

Nyati, Mukesh K.; Maheshwari, Divya; Hanasoge, Sheela; Sreekumar, Arun; Rynkiewicz, Susan D.; Chinnaiyan, Arul M.; Leopold, Wilbur R.; Ethier, Stephen P.; Lawrence, Theodore S.

doi:10.1158/1078-0432.ccr-1041-03

Cited by 78 publications

(58 citation statements)

References 29 publications

(30 reference statements)

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“…Potential cancer therapies must not only inhibit cell growth in vitro but also must be able to inhibit tumor growth in the complex in vivo environment. Several researchers have reported that CI-1033 treatment of athymic nude mice bearing xenografts of epidermoid carcinoma, non-small cell lung carcinoma, glioblastoma, and breast and colon cancer results in highly significant suppression of tumor growth (26,27,50). Our study showed that treatment with CI-1033 completely prevents the growth of esophageal squamous cell carcinoma xenografts.…”

Section: Discussionsupporting

confidence: 63%

“…Since cisplatin is one of the most active chemotherapeutic agents for the treatment of esophageal cancer, enhanced antitumor activity by the combination of this drug and CI-1033 may be observed in clinical trials. In addition, some studies indicate that CI-1033 has synergistic effects when combined with ionizing radiation in breast, colon cancer and bile duct carcinoma (27,28,52). If CI-1033 is used in esophageal cancer therapy in the future, the concurrent use of other treatment strategies, such as chemoradiotherapy, should be included.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that CI-1033 inhibits the growth of cancer cells including glioblastoma, bile duct, breast and colon cancer (24,(26)(27)(28)(29). Treatment of athymic nude mice bearing xenografts of various tumors with CI-1033 results in highly significant suppression of tumor growth.…”

Section: Introductionmentioning

confidence: 99%

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The pan-erbB tyrosine kinase inhibitor CI-1033 inhibits human esophageal cancer cells in vitro and in vivo

Ako

Yamashita²,

Ohira³

et al. 2007

Oncol Rep

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Abstract. The epidermal growth factor receptor (EGFR) is a member of the EGFR family of receptors. EGFR and other members of the EGFR family have been shown to play significant roles in human cancer cell proliferation and therefore present important molecular targets for the treatment of cancer. The purpose of this study was to examine the effect of the pan-erbB tyrosine kinase inhibitor CI-1033 against esophageal squamous cell carcinoma in vitro and in vivo. We selected 4 human esophageal squamous cell carcinoma cell lines (TT, TE2, TE6, and TE10), and determined their expression of EGFR and HER2. We examined the ability of CI-1033 to inhibit cell growth in vitro and in vivo. EGFR and HER2 were overexpressed in all 4 esophageal cancer cells. We found that CI-1033 could inhibit the growth of esophageal cancer cell lines in a dose-dependent manner with the inhibition of phosphorylation of both MAPK and AKT. The oral administration of CI-1033 exerted a significant antitumor effect on esophageal cancer tumors in athymic nude mice. Our results suggest that CI-1033 effectively inhibits the growth of esophageal squamous cell carcinoma which co-expresses both EGFR and HER2 with the inhibition of phosphorylation of both MAPK and AKT. Furthermore, in vivo animal studies of CI-1033 suggest that CI-1033 holds significant clinical potential in esophageal cancer.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The pan-erbB tyrosine kinase inhibitor CI-1033 inhibits human esophageal cancer cells in vitro and in vivo

Ako

Yamashita²,

Ohira³

et al. 2007

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…1A). Consistent with our data, high expression of ErbB1 and/or ErbB2 in both cell lines was reported in previous studies (16)(17)(18). As expected based on the ErbB protein expression data, the proliferation of both cells was stimulated by heregulin in a concentration-dependent manner.…”

Section: Mitogenic Effect Of Heregulin In Erbb-expressing Colon Cancesupporting

confidence: 94%

Effect of butyrate on the heregulin/ErbB-mediated proliferation of human colorectal cancer cells

Lim

Choi²,

Kim³

et al. 2009

Mol Med Rep

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Abstract. The expression of ErbB proteins, together with heregulin, was found to be increased in colon cancer cells compared with normal mucosa, and heregulin-stimulated activation of ErbB signaling was observed to contribute to the proliferation of colon cancer cells. Butyrate produced during the fermentation of fiber by intestinal bacteria is known to exert diverse anticancer effects, including the induction of differentiation, cell cycle arrest and growth suppression in human colon cancer cells. In this study, we investigated whether butyrate affects the heregulin/ErbB-mediated proliferation of colon cancer cells. The growth of human CaCo-2 and SNU-C4 colon cancer cells, which express ErbB1-4 proteins, was stimulated by heregulin in a concentrationdependent manner. Pretreatment with sodium butyrate abolished heregulin-stimulated proliferation in both cell lines. Although butyrate did not alter ErbB protein expression and activation, it did block the prolonged activation of Akt and Erk1/2, which are known to be important ErbB downstream molecules mediating heregulin-stimulated proliferation. Our data suggest that the inhibitory effects of butyrate on the heregulin-stimulated proliferation of colorectal cancer cells are, in part, associated with the suppression of the Akt and Erk signaling pathway. Butyrate may act as a preventive and therapeutic agent in the progression of colorectal cancer through the regulation of heregulin-stimulated mitogenic signaling.

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“…After cells were harvested in TRIzol (Invitrogen Co., Carlsbad, CA, USA), RNA was extracted and reverse transcribed into cDNA as described previously (Nyati et al, 2004). Quantitative PCR (QPCR) was then performed using SYBR Green dye on an Applied Biosystems 7300 Real-time PCR system (Applied Biosystems, Foster City, CA, USA) as described previously (Tomlins et al, 2005).…”

Section: Rna Isolation and Quantitative Pcrmentioning

confidence: 99%

Role of epidermal growth factor receptor degradation in gemcitabine-mediated cytotoxicity

et al. 2006

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We have recently reported that treatment with gemcitabine, a potent chemotherapeutic agent and radiation sensitizer, stimulates phosphorylation of the epidermal growth factor receptor (EGFR). Because phosphorylation of EGFR is known to precede receptor degradation, we hypothesized that gemcitabine treatment may also result in EGFR degradation. In two human head and neck cancer cell lines, UMSCC-1 and UMSCC-6, we demonstrated an approximately 80% decrease in total EGFR levels at 72 h after a 2-h treatment with 1 lM gemcitabine. Neither cisplatin nor 5-fluorouracil, which are used to treat head and neck cancer, caused EGFR degradation. EGFR downregulation did not occur at the level of transcription, as assessed by reverse transcription-polymerase chain reaction (RT-PCR), but instead occurred via phosphorylation and ubiquitination of the receptor along a proteosome/lysosome-mediated pathway. Inhibition of EGFR degradation, by either pretreatment with the EGFR tyrosine kinase inhibitor gefitinib or by exposure to the proteosome/lysosome inhibitor MG132, significantly reduced gemcitabine-induced cell death. These results suggest that EGFR degradation may be a novel mechanism for gemcitabine-mediated cell death. These findings also indicate that caution should be exercised when combining gemcitabine with agents that may prevent EGFR degradation, such as EGFR tyrosine kinase inhibitors administered in a suboptimal sequence or proteosome inhibitors.

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Radiosensitization by Pan ErbB Inhibitor CI-1033 in Vitro and in Vivo

Cited by 78 publications

References 29 publications

The pan-erbB tyrosine kinase inhibitor CI-1033 inhibits human esophageal cancer cells in vitro and in vivo

The pan-erbB tyrosine kinase inhibitor CI-1033 inhibits human esophageal cancer cells in vitro and in vivo

Effect of butyrate on the heregulin/ErbB-mediated proliferation of human colorectal cancer cells

Role of epidermal growth factor receptor degradation in gemcitabine-mediated cytotoxicity

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