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The significance of LIM domain only 2 expression in the progression of adenoid cystic carcinoma
Free Papers—Poster Presentations (VEGFR), AEE788 in a subcutaneous (ectopic) and a mouth floor (orthotopic) tumour models. Nude mice with subcutaneous tumours were randomised to receive C225 alone, paclitaxel alone, C225 plus paclitaxel, or a placebo. And nude mice with orthotopic tumours were randomised to receive AEE788, paclitaxel, a combination of AEE788 and paclitaxel, or control. Antitumour mechanisms were determined by immunohistochemical assays. Results: Tumours of mice treated with C225 demonstrated down-regulation of activated EGFR, decreased proliferative index, decreased microvessel density (MVD), which slowed growth of the murine tumour. Furthermore, the inhibitory effect on the tumour growth was potentiated by paclitaxel. Tumours of mice treated with AEE788 exhibited down-regulation of activated EGFR and VEGFR-2, and their downstream mediators, decreased proliferative index, decreased MVD. As a result, growth of the orthotopic tumour and metastatic potentials were inhibited by AEE788. Conclusion: These data show that EGFR and VEGFR can be molecular targets for the treatment of OSCC. Acknowledgement. This study was supported by a grant of the Korea Healthcare technology R and D Project, Ministry of Health and Welfare, Republic of Korea. (A080293)
Further, stable introduction of LMO2 into Acc-M which lacked this protein was performed to evaluate the role of LMO2 by investigating the change of cell proliferation, cell migration and tumour formation, and the effect of LMO2 in tumour-induced angiogenesis was tested by endothelial cells tube formation assay, chicken chorioallantoic membrane (CAM) assay and the Matrigel plug angiogenesis assay. In addition, the expression level of vascular endothelial growth factor (VEGF) was examined by Real time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Immunoreactivity for LMO2 was detected in all ACCs with specific location in the nucleus and cytoplasm, and its expression level had significant correlation with MVD (P < 0.01). Overexpression of LMO2 in Acc-M promoted tumourinduced angiogenesis while it could not influence the proliferation, migration and tumour formation of tumour cells, accompanied by up-regulation of VEGF. Conclusions: These results first demonstrated that LMO2 may play a critical role in angiogenesis through up-regulating VEGF expression, and consequently influence tumour metastasis of ACCs, suggesting that LMO2 may be a new anti-angiogenesis drug target in ACCs. doi:10.1016/j.ijom.2009.03.486
doi:10.1016/j.ijom.2009.03.485
P13 The significance of LIM domain only 2 expression in the progression of adenoid cystic carcinoma Y. Cai ∗ , Z.J. Sun, J. Jia, Y.F. Zhao Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Background and Objectives: Angiogenesis played an important role in tumour growth and tumour metastasis of adenoid cystic carcinomas (ACCs). Recent research found that LIM domain only 2 (LMO2) was essential for angiogenesis in normal tissue and tumour. The objective of this study was to explore the expression and effect of LMO2 in ACCs. Methods: In a retrospective study, immunoreactivity for LMO2 were assessed in 50 surgically resected ACCs and microvessel density (MVD) was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters.
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Methods: ACC-M (high metastasis) and ACC-2 (low metastasis) cell lines were set up to investigate the effects of curcumin on cell proliferation, apoptosis, invasion and tumour-induced angiogenesis, as well as the possible underlying mechanisms. Furthermore, the in vivo effects of curcumin were examined using nude mouse xenograft models. Results: Curcumin dose-dependently decreased the survival of ACC cells via G2-M arrest and induction of apoptosis. The ability of ACC cells to invade and induce angiogenesis was also significantly inhibited in the presence of curcumin, accompanied by down-regulation of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2, and MMP-9 expression. In addition, the data also showed that the inhibitory effects of curcumin on ACC cells were due to the dual inhibition of both mTOR and nuclear factor-kappaB pathway through a PI3K/Akt/IKKbeta signalling axis. Most importantly, curcumin significantly prevented in vivo growth and angiogenesis as revealed by induction of cell apoptosis and reduction of microvessel density (MVD) in tumour tissues. Conclusion: Our results implicated that further clinical investigation should be warranted to apply curcumin as a novel prevention regimen for ACC progression. doi:10.1016/j.ijom.2009.03.487
P14 Curcumin prevents tumour growth, angiogenesis, and invasion in adenoid cystic carcinoma by dual inhibition of both mTOR and nuclear factor-kappaB pathway through a PI3K/Akt/IKKbeta signalling axis Z.J. Sun ∗ , G. Chen, X. Hu, W. Zhang Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei Province, China
Background and Objectives: Adenoid cystic carcinoma (ACC) is a highly malignant tumour that is generally unresponsive or only weakly responsive to the currently available antineoplastic agents. Thus novel therapeutic strategies and agents are urgently needed to treat this incurable cancer. Curcumin, a component of turmeric (Curcuma longa), has been shown to have a diversity of anti-tumour activities. Here, we explored the effects of curcumin on tumour growth, angiogenesis, and invasion of ACC.
P15 Increased salivary acetaldehyde levels in poor dental health status: a possible link to increased oral cancer risk H. Kocaelli 1,∗ , A. Apaydin 1 , A. Karadeniz 2 , S. Ozel 3 1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Istanbul University, Istanbul, Turkey 2 Department of Radiation Oncology, Faculty of Medicine, Istanbul University, Istanbul, Turkey 3 Department of Biostatistics and Demography, Faculty of Medicine, Istanbul University, Istanbul, Turkey
Background and Objectives: Acetaldehyde, the fist metabolite of alcohol, has been proposed to be carcinogenic substance behind ethanol-related oral cancers. In this study we investigated the factors that might alter the composition and quantities of the oral microflora and, consequently, influence salivary acetaldehyde production in healthy and oral cancer patients.
Further, stable introduction of LMO2 into Acc-M which lacked this protein was performed to evaluate the role of LMO2 by investigating the change of cell proliferation, cell migration and tumour formation, and the effect of LMO2 in tumour-induced angiogenesis was tested by endothelial cells tube formation assay, chicken chorioallantoic membrane (CAM) assay and the Matrigel plug angiogenesis assay. In addition, the expression level of vascular endothelial growth factor (VEGF) was examined by Real time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Immunoreactivity for LMO2 was detected in all ACCs with specific location in the nucleus and cytoplasm, and its expression level had significant correlation with MVD (P < 0.01). Overexpression of LMO2 in Acc-M promoted tumourinduced angiogenesis while it could not influence the proliferation, migration and tumour formation of tumour cells, accompanied by up-regulation of VEGF. Conclusions: These results first demonstrated that LMO2 may play a critical role in angiogenesis through up-regulating VEGF expression, and consequently influence tumour metastasis of ACCs, suggesting that LMO2 may be a new anti-angiogenesis drug target in ACCs. doi:10.1016/j.ijom.2009.03.486
doi:10.1016/j.ijom.2009.03.485
P13 The significance of LIM domain only 2 expression in the progression of adenoid cystic carcinoma Y. Cai ∗ , Z.J. Sun, J. Jia, Y.F. Zhao Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Background and Objectives: Angiogenesis played an important role in tumour growth and tumour metastasis of adenoid cystic carcinomas (ACCs). Recent research found that LIM domain only 2 (LMO2) was essential for angiogenesis in normal tissue and tumour. The objective of this study was to explore the expression and effect of LMO2 in ACCs. Methods: In a retrospective study, immunoreactivity for LMO2 were assessed in 50 surgically resected ACCs and microvessel density (MVD) was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters.
535
Methods: ACC-M (high metastasis) and ACC-2 (low metastasis) cell lines were set up to investigate the effects of curcumin on cell proliferation, apoptosis, invasion and tumour-induced angiogenesis, as well as the possible underlying mechanisms. Furthermore, the in vivo effects of curcumin were examined using nude mouse xenograft models. Results: Curcumin dose-dependently decreased the survival of ACC cells via G2-M arrest and induction of apoptosis. The ability of ACC cells to invade and induce angiogenesis was also significantly inhibited in the presence of curcumin, accompanied by down-regulation of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2, and MMP-9 expression. In addition, the data also showed that the inhibitory effects of curcumin on ACC cells were due to the dual inhibition of both mTOR and nuclear factor-kappaB pathway through a PI3K/Akt/IKKbeta signalling axis. Most importantly, curcumin significantly prevented in vivo growth and angiogenesis as revealed by induction of cell apoptosis and reduction of microvessel density (MVD) in tumour tissues. Conclusion: Our results implicated that further clinical investigation should be warranted to apply curcumin as a novel prevention regimen for ACC progression. doi:10.1016/j.ijom.2009.03.487
P14 Curcumin prevents tumour growth, angiogenesis, and invasion in adenoid cystic carcinoma by dual inhibition of both mTOR and nuclear factor-kappaB pathway through a PI3K/Akt/IKKbeta signalling axis Z.J. Sun ∗ , G. Chen, X. Hu, W. Zhang Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei Province, China
Background and Objectives: Adenoid cystic carcinoma (ACC) is a highly malignant tumour that is generally unresponsive or only weakly responsive to the currently available antineoplastic agents. Thus novel therapeutic strategies and agents are urgently needed to treat this incurable cancer. Curcumin, a component of turmeric (Curcuma longa), has been shown to have a diversity of anti-tumour activities. Here, we explored the effects of curcumin on tumour growth, angiogenesis, and invasion of ACC.
P15 Increased salivary acetaldehyde levels in poor dental health status: a possible link to increased oral cancer risk H. Kocaelli 1,∗ , A. Apaydin 1 , A. Karadeniz 2 , S. Ozel 3 1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Istanbul University, Istanbul, Turkey 2 Department of Radiation Oncology, Faculty of Medicine, Istanbul University, Istanbul, Turkey 3 Department of Biostatistics and Demography, Faculty of Medicine, Istanbul University, Istanbul, Turkey
Background and Objectives: Acetaldehyde, the fist metabolite of alcohol, has been proposed to be carcinogenic substance behind ethanol-related oral cancers. In this study we investigated the factors that might alter the composition and quantities of the oral microflora and, consequently, influence salivary acetaldehyde production in healthy and oral cancer patients.