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Diane E Milenic Karen J Wong Kwamena E Baidoo Tapan K Nayak Celeste AS Regino Kayhan Garmestani Martin W Brechbiel 《MABS-AUSTIN》2010,2(5):550-564
The potential of the HER2-targeting antibody trastuzumab as a radioimmunoconjugate useful for both imaging and therapy was investigated. Conjugation of trastuzumab with the acyclic bifunctional chelator CHX-A″-DTPA yielded a chelate:protein ratio of 3.4 ± 0.3; the immunoreactivity of the antibody unaffected. Radiolabeling was efficient, routinely yielding a product with high specific activity. Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian and prostate carcinomas. High uptake of the radioimmunoconjugate, injected intravenously (i.v.), was observed in each of the models and the highest tumor %ID/g (51.18 ± 13.58) was obtained with the ovarian (SKOV-3) tumor xenograft. Specificity was demonstrated by the absence of uptake of 111In-trastuzumab by melanoma (A375) s.c. xenografts and 111In-HuIgG by s.c. LS-174T xenografts. Minimal uptake of i.v. injected 111In-trastuzumab in normal organs was confirmed in non-tumor-bearing mice. The in vivo behavior of 111In-trastuzumab in mice bearing intraperitoneal (i.p.) LS-174T tumors resulted in a tumor %ID/g of 130.85 ± 273.34 at 24 h. Visualization of tumor, s.c. and i.p. xenografts was achieved by γ-scintigraphy and PET imaging. Blood pool was evident as expected but cleared over time. The blood pharmacokinetics of i.v. and i.p. injected 111In-trastuzumab was determined in mice with and without tumors. The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies, a Phase 0 imaging study in the Molecular Imaging Program of the National Cancer Institute and a Phase 1 radioimmunotherapy study at the University of Alabama.Key words: monoclonal antibody, HER2, trastuzumab, radioimmunodiagnosis, radioimmunotherapy 相似文献
63.
Background
Benchmarking algorithms in structural bioinformatics often involves the construction of datasets of proteins with given sequence and structural properties. The SCOP database is a manually curated structural classification which groups together proteins on the basis of structural similarity. The ASTRAL compendium provides non redundant subsets of SCOP domains on the basis of sequence similarity such that no two domains in a given subset share more than a defined degree of sequence similarity. Taken together these two resources provide a 'ground truth' for assessing structural bioinformatics algorithms. We present a small and easy to use API written in python to enable construction of datasets from these resources. 相似文献64.
FREE CHOICE PROFILING OF CHILEAN GOAT CHEESE 总被引:1,自引:0,他引:1
Different goat cheeses from Chile were studied by Free-Choice Profile (FCP) analysis. Generalized Procrustes Analysis (GPA) applied to FCP data permitted differentiation between samples and informed on the attributes responsible for the observed differences. Appearance was a dominant factor in discriminating samples and to a lesser degree textural variables were also correlated with GPA dimensions. In acceptability the fresh cheeses were significantly preferred over the ripened ones. 相似文献
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Patrick Martin Benjamin AS Van Mooy Abigail Heithoff Sonya T Dyhrman 《The ISME journal》2011,5(6):1057-1060
In low-phosphorus (P) marine systems, phytoplankton replace membrane phospholipids with non-phosphorus lipids, but it is not known how rapidly this substitution occurs. Here, when cells of the model diatom Thalassiosira pseudonana were transferred from P-replete medium to P-free medium, the phospholipid content of the cells rapidly declined within 48 h from 45±0.9 to 21±4.5% of the total membrane lipids; the difference was made up by non-phosphorus lipids. Conversely, when P-limited T. pseudonana were resupplied with P, cells reduced the percentage of their total membrane lipids contributed by a non-phosphorus lipid from 43±1.5 to 7.3±0.9% within 24 h, whereas the contribution by phospholipids rose from 2.2±0.1 to 44±3%. This dynamic phospholipid reservoir contained sufficient P to synthesize multiple haploid genomes, suggesting that phospholipid turnover could be an important P source for cells. Field observations of phytoplankton lipid content may thus reflect short-term changes in P supply and cellular physiology, rather than simply long-term adjustment to the environment. 相似文献
67.
Background
There are four widely used experimental strains of N. gonorrhoeae, one of which has been sequenced and used as the basis for the construction of a multi-strain, mutli-species pan-neisserial microarray. Although the N. gonorrhoeae population structure is thought to be less diverse than N. meningitidis, there are some recognized gene-complement differences between strains, including the 59 genes of the Gonococcal Genetic Island. In this study we have investigated the three experimental strains that have not been sequenced to determine the extent and nature of their similarities and differences. 相似文献68.
Gomes AC Miranda I Silva RM Moura GR Thomas B Akoulitchev A Santos MA 《Genome biology》2007,8(10):R206
Background
Genetic code alterations have been reported in mitochondrial, prokaryotic, and eukaryotic cytoplasmic translation systems, but their evolution and how organisms cope and survive such dramatic genetic events are not understood. 相似文献69.
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