For cell survival studies, each treatment concentration was examined three times and in triplicate samples. The effect of saposin C or other effec tors in the presence of etoposide on cell growth, apopto sis, or caspase 3/7 activity was studied in Nilotinib msds twelve replicates and repeated three times. Statistical significance was set at p 0. 05 or 0. 01. Statistical analyses were performed using GraphPad Inhibitors,Modulators,Libraries Prism version 3. 00 for Windows. Background Vitamin A containing cells were first reported in 1982 by Watari et al. in vitamin A loaded mice using fluorescence and electron microscopy. This cell type was subse quently identified by electron microscopy in normal rat and human pancreatic tissues. These cells were identi fied as pancreatic stellate cells by Apte et al and Bachem et al in 1998.

In the normal pancreas, stel late cells are quiescent and can be identified by the pres ence of vitamin Inhibitors,Modulators,Libraries A containing lipid droplets in the cytoplasm. In response to pancreatic injury or inflamma tion, PSCs are transformed from quiescent phenotypes into highly proliferative myofibroblast like cells which express the cytoskeletal protein smooth including PGs, prostacyclin, and thromboxanes. Two iso zymes are found in mammalian tissues, COX 1 and COX 2. COX 1 is expressed constitutively in a wide variety of tissues, Inhibitors,Modulators,Libraries where it is involved in the maintenance of tissue homeostasis. In contrast, COX 2, which is not expressed in resting cells, is the inducible form of the enzyme responsible for PG production at sites of inflammation. Growth factors, cytokines, tumor promoters, and other inflammatory mediators can induce COX 2 expression.

COX 2 expression and activity is up regulated in pancreatic cancer, but Inhibitors,Modulators,Libraries absent in normal pancreatic acinar and duct cells. Some scattered cells in normal pan creatic tissues express COX 2. The current study revealed that COX 2 is expressed in pri mary cultured PSC. Furthermore, conditioned media from pancreatic cancer stimulates PSC proliferation and COX 2 expression. The increase in PSC proliferation in response to conditioned media is prevented by inhibition of COX 2. Results COX 2 in primary cultured PSCs In early primary PSCs, cytoplasmic COX 2 staining was muscle actin, and produce type I collagen and other extracellular matrix components. Many of the mor phological and metabolic changes associated with the activation of PSCs in animal models of fibrosis also occur when these cells are cultured on plastic in serum contain ing medium.

Activated PSCs have also been Inhibitors,Modulators,Libraries implicated in the deposi tion of extracellular matrix components in pancreatic ade nocarcinoma. In patients with pancreatic cancer, an intense, interstitial, fibrillar staining for PSCs is evident in the peritumoral fibrous regions. Procollagen I staining colocalized with SMA to these fibroblast shaped cells suggests that http://www.selleckchem.com/products/BAY-73-4506.html they are responsible for the deposition of matrix components and the desmoplastic reaction that surrounds the pancreatic tumor.