The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The use of polyethylene glycol-modified interleukin-2 (PEG- IL-2) in the treatment of patients with metastatic renal cell carcinoma and melanoma. A phase I study and a randomized prospective study comparing IL-2 alone versus IL-2 combined with PEG- IL-2.

BACKGROUND. Conjugation of polyethylene glycol to recombinant human interleukin-2 ( IL-2) results in a compound, polyethylene glycol-modified IL-2 (PEG- IL-2) that retains the in vitro and in vivo activity of IL-2, but exhibits a markedly prolonged circulating half-life. In mice, one dose of PEG- IL-2 results in tumor regression comparable to that achieved with multiple bolus doses of IL-2. Based on these preclinical studies, a Phase I study with PEG- IL-2 was undertaken in patients with metastatic renal cell carcinoma (RCC) and melanoma. Then, to exploit the higher peak levels attained with IL-2 and the improved trough levels of PEG- IL-2, a combination regimen beginning with bolus IL-2 followed by low dose maintenance PEG- IL-2 was devised and tested for efficacy. METHODS. Patients with measurable metastatic melanoma or RCC were entered in a Phase I dose escalation trial of PEG- IL-2 given once a week by intravenous bolus. This trial then was repeated using a twice-a-week schedule. After determining the maximum tolerated dose (MTD) and a safe outpatient regimen for PEG- IL-2, a hybrid regimen combining an initial high dose IL-2 cycle followed by chronic maintenance with weekly PEG- IL-2 was devised. This regimen was compared with a standard regimen consisting of two cycles of high dose unconjugated IL-2 in a randomized prospective clinical trial. RESULTS. When given by intravenous bolus once a week, the MTD of PEG- IL-2 was 12 million IU/m2, with toxicities similar to those of unconjugated IL-2. A twice-a-week schedule was less well tolerated. Of 28 patients given 32 treatment courses at varied dose levels, there were two partial responses and one minor response. A total of 124 patients with metastatic melanoma or RCC were randomized to either standard unconjugated IL-2 therapy or the hybrid regimen. There was no treatment-related mortality in either arm, and the use of PEG- IL-2 resulted in a significant decrease in the need for intensive-care-unit care. The response rates (partial response and complete response) for patients with RCC and melanoma were 19% and 15%, respectively, for IL-2 alone and 17% and 11%, respectively, for the IL-2 and PEG- IL-2 combination. CONCLUSIONS. The combination of high dose IL-2 followed by PEG- IL-2 is a well tolerated regimen with significant activity against RCC and melanoma, but it shows no significant increase in antitumor activity compared with high dose IL-2 alone.[1]


WikiGenes - Universities