Inhibitors of the epidermal growth factor receptor family, such as erlotinib, cetuximab, and lapatinib were recently investigated. Bortezomib, an inhibitor of the proteasome; imatinib mesylate, an inhibitor of c-kit; bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF); and Sorafenib (BAY 43-9006), a multiple kinase inhibitor that blocks not only Sorafenib Tosylate Sigma receptor tyrosine kinases but also serine/threonine kinases along the RAS/RAF/MEK/ERK pathway, have also been studied. Although early evidence of antitumor activity was seen, the results are still preliminary and require further investigations. Applications The aim of the authors�� study was to investigate the in vitro treatment with NVP-AEW541, a small molecule inhibitor of insulin-like growth factor-1 receptor (IGF-1R), in BTC.

Their findings suggested that cell growth supression was successful in seven human BTC cell lines. Combined with gemcitabine, NVP-AEW541 exerted synergistic effects, particularly at low concentrations, while effects of combinations with 5-fluorouracil or Polo-like kinase 1 inhibitor BI 2536 were only additive. Terminology The IGF-1R system has emerged as an interesting target for cancer therapy, as it represents an important promoter of tumor transformation and survival of malignant cells, but is only partially involved in normal cell growth. This is in part attributed to interactions with oncogenes. Moreover, activation of IGF-1R may contribute to tumor angiogenesis by up-regulation of VEGF expression in certain cancer entities.

In the past, different strategies were used to inhibit IGF-1R function, among them monoclonal antibodies and anti-sense RNA directed against the receptor, or recombinant IGF binding proteins and IGF-specific antibodies to reduce levels of ligands. Peer review The strength of this manuscript is that it characterized a highly-resistant BTC cell line in comparison with an extrahepatic CC cell line. Also, to some extent, the mechanism leading to the resistance was examined. Acknowledgments The authors thank Annett Kluge and Ines Sommerer for technical assistance, Novartis Pharma for the provision of NVP-AEW541 and Boehringer-Ingelheim for the provision of BI 2536. Footnotes Supported by Grant No.

934000-258 from Novartis Oncology (to Wiedmann M) Peer reviewer: Shiu-Ming Kuo, MD, University at Buffalo, 15 Farber Hall, 3435 Main Street, Buffalo, NY 14214, United States S- Editor Tian L L- Editor Logan S E- Editor Zheng XM
AIM: To determine the frequency and clinical impact of incidental findings detected with magnetic resonance imaging (MRI)-enterography in patients with suspected or known Crohn��s disease (CD). METHODS: Incidental findings were defined as unexpected lesions outside the small intestine, not previously known or suspected at the time of referral, GSK-3 and not related to inflammatory bowel disease.