Ribosome inhibiting proteins are a group of highly potent plant lectins, which can kill tumor cells at nano- to picomolar concentrations. This includes modification of established therapies and testing of new substances. It was shown that chemo-radiation is superior to best supportive care and to radiotherapy alone, but more toxic and equally effective in comparison to chemotherapy alone ( 7).Īltogether, the relatively poor efficacy of chemotherapy and chemo-radiation against this devastating disease indicates that the development of new therapeutic strategies is a crucial step to improve the survival of advanced PDAC. The efficacy of chemo-radiation in advanced PDAC has been evaluated in many randomised trials. 6.7 months following gemcitabine alone ( 6). This combination was even superior to the recently published combination of gemcitabine with nab-paclitaxel, which resulted in a median survival time of 8.5 months vs.
Rpx report file stands for trial#
In addition, a recent randomized trial with FOLFIRINOX has enhanced the median overall survival, when compared with GEM (11.1 months vs. However, many trials with other drugs in combination with GEM were investigated in the last decade a combination of GEM and oxaliplatin has shown a benefit in a phase II study ( 5). 5-Fluorouracil has also some clinical activity against advanced PDACA with a median overall survival of 4.4 months ( 2). GEM has significantly improved the median overall survival of PDAC patients by 1.2 months over patients treated with 5-fluorouracil and became the reference drug for this disease ( 4). The most effective single chemotherapy intervention against advanced PDAC has been achieved with gemcitabine (GEM).
Despite radical surgical intervention (R0 resection) and chemo-radiation, the survival for all stages at 5 years is about 6% in Europe and the United States ( 2, 3). The incidence of PDAC continues to increase and ranks as fourth cause of cancer related mortality. Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses of all malignancies worldwide ( 1). Further experiments are required in order to elucidate its affinity for certain cancer cells and to optimize the combination therapy with other antineoplastic agents. These results suggest that Rpx has an evident potential for use in pancreatic cancer treatment. In addition, DIN was ineffective, and in combination, reduced the activity of Rpx. The standard drug GEM alone was less effective compared with Rpx. Higher doses of Rpx caused no further reduction in tumor size when compared with the low dose of Rpx or a combination of Rpx with GEM, or DIN. The survival rate of rats was significantly increased (21.8 days for Rpx treated vs. Rpx inhibited ASML cell proliferation at IC 50-values of 0.8–172 pM, caused apoptosis and reduced tumor growth significantly by 90% (P<0.05). Rpx was administered intraperitoneally at doses of 1.7–5.4 µg/kg, three times/week, GEM was administered intravenously (50 mg/kg/week) and DIN perorally (10 mg/kg, 5 times/week). Tumor-bearing nude rats were treated with Rpx, gemcitabine (GEM) or dinaline (DIN) as single agents, or a combination of Rpx with GEM, or DIN. The modulation of proteins involved in apoptosis was evaluated using western blotting. The antiproliferative effect of Rpx was assessed using an MTT assay.
The rat PDAC cell line ASML was used for in vitro and in vivo studies. The ribosome inactivating protein of type II exhibits potent anticancer activity as recently demonstrated. Riproximin (Rpx) is a newly identified plant lectin, which was isolated from Ximenia americana. To improve the survival of patients with PDAC, the development of novel anticancer agents is warranted. Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses of all malignancy types.
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