Since combination therapy is key to improving cancer treat ment efficacy, these results may guide the development of novel therapeutic approaches to cancer. Background Survival following diagnosis of non small cell lung can cer is poor despite www.selleckchem.com/products/CP-690550.html therapy. Hypoxia is typ ically present in solid tumors like lung cancer and is known to enhance tumor progression and therapy resist ance. The effects of hypoxia are largely mediated by the hypoxia inducible factors HIF 1 and HIF 2. HIFs induce the expression of many differ ent proteins that are involved in key functions of cancer cells, including cell survival, metabolic reprogramming, angiogenesis, invasion, and metastasis. Under normoxic conditions, HIFs are rapidly degraded, while under hypoxia they are stabilized.

In addition to oxygen dependent regulation, HIFs can be up regulated by other mecha nisms, e. g. growth factor induced pathways. The biological response of tumors to hypoxia is influenced by the interplay of neoplastic cancer cells and the sur rounding Inhibitors,Modulators,Libraries stroma cells, e. g. cancer associated fibroblasts. Ex vivo human cancer models based on the short term culture of small tumor fragments or slices are suitable to study tumor responses within the nat ural in situ microenvironment, comprising a close con tact between tumor cells and the accompanying stroma cells. Such models have been used e. g. for the study of drug effects in lung cancer and other cancers. Here we used a human ex vivo lung cancer model involv ing culture of fresh tumor fragments in a hypoxic at mosphere to mimic in vivo tumor hypoxia and performed a comparative expression profiling study.

We found that hypoxia led to overexpression of a Inhibitors,Modulators,Libraries stem cell marker Inhibitors,Modulators,Libraries with elastase activity, membrane metallo endopeptidase, in tumor fragments, which was attributable to Inhibitors,Modulators,Libraries carcinoma associated fibroblasts, not the neoplastic can cer cells. Methods Inhibitors,Modulators,Libraries Lung cancer fragments Tumor tissue samples from 70 consecutive patients with NSCLC who were referred for surgical resection to the Division of Thoracic and Hyperbaric Surgery, Medical University of Graz, from May 2007 to May 2013, were included in the study. Patients with pre operative chemo therapy were excluded from the study. Surgical specimens were dissected into small fragments using a razor blade and fragments were incubated in 35 mm Petri dishes in 2 ml of DMEM F 12 growth medium containing 10% fetal calf serum, 2 mM L glutamine, 100 U ml penicillin, and 100 ug ml streptomycin.

The study protocol www.selleckchem.com/products/XL184.html was approved by the ethics review board of the Medical University of Graz. Signed informed consent was obtained from all patients prior to surgery. Cells The human NSCLC cell lines A549 and A427 were pur chased from Cell Lines Service and cultured in DMEM F 12 medium containing the sup plements described above.