“We have published the dynamic extended folding (DEF) method which is a RNA secondary structure prediction approach to simulate the in vivo RNA co-transcriptional folding process In order to verify the reliability of the method we selected the X-ray-determined Tetrahymena group I intron as a sample to construct the framework of its Mocetinostat supplier folding secondary structure Our prediction coincides well with the secondary structure predicted by T R. Cech and the X-ray diffraction crystal structure determined by Lehnert V Our results show that the DEF framework structure of Tetrahymena
group I intron reflects its function sites in a concise and straightforward manner and the scope of the simulation was expanded (C) 2010 Elsevier Ltd All rights reserved”
Stimulating an immune response against cancer with the use of vaccines remains a challenge. Selleckchem Savolitinib We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2
We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA(star)A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose)
Idoxuridine or gp100: 209-217(210M) plus incomplete Freund’s adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end point was clinical response. Secondary end points included toxic effects and progression-free survival.
The treatment groups were well balanced with respect to baseline characteristics and received a similar amount of interleukin-2 per cycle. The toxic effects were consistent with those expected with interleukin-2 therapy. The vaccine-interleukin-2 group, as compared with the interleukin-2-only group, had a significant improvement in centrally verified overall clinical response (16% vs. 6%, P=0.03), as well as longer progression-free survival (2.2 months; 95% confidence interval [CI], 1.7 to 3.9 vs. 1.6 months; 95% CI, 1.5 to 1.8; P=0.008). The median overall survival was also longer in the vaccine-interleukin-2 group than in the interleukin-2-only group (17.8 months; 95% CI, 11.9 to 25.8 vs. 11.1 months; 95% CI, 8.7 to 16.3; P=0.06).
In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00019682.