Cleaved bands greater than 5 fold over the control were shown at 3. 5M with all incubation periods. PARP can release apoptosis inducing factor, which induces chromatin condensation and large scale DNA fragmentation when released into the cytosol. Simi lar to PARP, AIF cleavage was shown at concentrations www.selleckchem.com/products/Nilotinib.html greater than 0. 35M. Cleaved bands Inhibitors,Modulators,Libraries of AIF greater than 2 fold and were shown at 3. 5M at 24 hrs. Determination of Anti lymphoma Effect of ApoG2 in SCID Mice Previous studies in this laboratory indicated that the MTD for ApoG2 could not be determined. We tested up to 800 mg/kg iv of ApoG2. testing beyond 800 mg/kg were not attempted, due to cost and other logistical issues. For this efficacy trial, 5 106 WSU FSCCL cells were injected into the intraperitoneal cavity of 7 mice per group.

Seven days post WSU FSCCL inoculation, 25 mg/kg of ApoG2 was injected into each animal either Inhibitors,Modulators,Libraries intravenously or intraperitoneally over 5 days. After 105 days, 42% of the i. v. treated Inhibitors,Modulators,Libraries animals, and 60% of the i. p. treated ani mals had died from FL. Statistical comparison of survival curves for i. v. treatment and untreated control show a chi square of 8. 005 and P 0. 0047. Statistical comparison of survival curves for i. p. treatment and untreated control show a chi square of Inhibitors,Modulators,Libraries 4. 397 and P 0. 0360. Pathological evaluation showed that ret roperitoneal lymph nodes were diffusely replaced by tumor cells in mice that died. The effec tiveness of ApoG2 was further demonstrated by bone marrow examination which was completely replaced by tumor cells by day 34 in control animals.

In Inhibitors,Modulators,Libraries con trast, ApoG2 treated mice showed normal bone marrow with no apparent tumor infiltration. Discussion FL has been increasing in incidence over the past three decades and is now the fifth most common malignancy in the United States. There are many approaches to the treatment of FL, but the goal of therapy has been to main tain the best quality of life and treat when a patient is at high risk or the disease progresses. Standard chemother apy regimens directed towards these low grade lympho mas still lack complete curative effects. This may be in part due to the overexpression of Bcl 2, a key molecule of resistance in indolent lymphoma. Overexpression of Bcl 2 has been implicated to play a significant role in the clin ical outcome of FL patients. A number of approaches have been sought to target overexpression of Bcl 2 in FL, e.

g. downregulation of Bcl 2 protein via antisense oligo nucleotides. Most recently, hydrophobic groove of the Bcl 2 family of anti apoptotic proteins has become a very attractive target for the design of SMIs. SMIs filling the hydrophobic groove mimic cognate proteins selleckchem such as Bax and Bid. SMIs directed against BH3 domains have been categorized into at least eight different chemi cal classifications. Laboratories, including this one, have been in the search to find novel small molecule inhibitors to Bcl 2.