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The frequency of metaphases without a Philadelphia chromosome was determined in mitogen-stimulated cultures of peripheral blood mononuclear cells (PBMC) and purified T lymphocytes (93% CD2-positive) from a patient with chronic myelogenous leukemia (CML) for 28 years. The PBMC cultures contained few Ph-negative cells (8%), but they constituted 92% of the metaphases in T cell cultures, indicating few if any Ph-positive T cells in the patient's circulation. The results demonstrate that T cells derived from the leukemic clone may fail to replace the non-neoplastic population even when CML arises in childhood and the patient survives for many years. This raises questions concerning the normal role of the bone marrow as a source of T cells after infancy, and also whether Ph-positive lymphocytes may be at a disadvantage for growth. 相似文献
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This literature review emphasizes the importance of teacher training, teaching strategies, parental involvement, curricular concerns, administrative support, and social/cultural factors on the impact of nutrition education programs at the elementary school level. The characteristics, implementation, and effectiveness of selected elementary nutrition education programs are reviewed, and instructional methods and materials shown effective through research are identified and discussed. 相似文献
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Tumor targeting by an aptamer. 总被引:10,自引:0,他引:10
Brian J Hicke Andrew W Stephens Ty Gould Ying-Fon Chang Cynthia K Lynott James Heil Sandra Borkowski Christoph-Stephan Hilger Gary Cook Stephen Warren Paul G Schmidt 《Journal of nuclear medicine》2006,47(4):668-678
Aptamers are small oligonucleotides that are selected to bind tightly and specifically to a target molecule. We sought to determine whether aptamers have potential for in vivo delivery of radioisotopes or cytotoxic agents. METHODS: TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in fluorescent and radiolabeled forms. After in vivo administration, uptake and tumor distribution of Rhodamine Red-X-labeled aptamer was studied by fluorescence microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor xenografts, biodistribution and imaging studies were performed using TTA1 radiolabeled with (99m)Tc. Tenascin-C levels and tumor uptake were studied in a variety of additional human tumor xenografts. To assess the effect of radiometal chelate on biodistribution, mercapto-acetyl diglycine (MAG(2)) was compared with diethylenetriaminepentaacetic acid and with MAG(2)-3,400-molecular-weight PEG (PEG(3,400)). RESULTS: Intravenous injection of fluorescent aptamer TTA1 produced bright perivascular fluorescence in a xenografted human tumor within 10 min. In the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with (99m)Tc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min, and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1 %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of 50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the (99m)Tc-labeled aptamer, images of glioblastoma and breast tumors were obtained by planar scintigraphy. Aptamer uptake, seen in several different human tumors, required the presence of the target protein, human tenascin-C. Modification of the MAG(2) radiometal chelator dramatically altered the uptake and clearance patterns. CONCLUSION: TTA1 is taken up by a variety of solid tumors including breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance from the blood and other nontarget tissues enables clear tumor imaging. As synthetic molecules, aptamers are readily modified in a site-specific manner. A variety of aptamer conjugates accumulate in tumors, suggesting imaging and potentially therapeutic applications. 相似文献
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R B Weiss 《Seminars in oncology》1992,19(5):458-477
All cancer chemotherapeutic agents, except altretamine, the nitrosoureas, and dactinomycin, have produced at least an isolated instance of a HSR. Certain drugs, such as L-asparaginase and mitomycin (administered intravesically), cause HSRs of significant degree in approximately 10% of patients. All four types of HSRs are represented in the reactions produced by antitumor drugs, although Type I is the most common. Some of the Type I reactions are IgE-mediated, and others are probably mediated by nonspecific release of vasoactive substances from targets such as mast cells. It is possible to continue therapy with some drugs, despite a prior HSR, if the prophylactic measures outlined in Table 2 are taken. An example of this is provided by taxol in which the lengthening of the infusion time and the administration of preventive medication allowed some patients to continue taxol therapy. The mechanisms of the HSRs have been carefully assessed in only a minority of patients who sustained such toxicity. Such evaluation would increase our understanding of this form of drug toxicity and perhaps lead to means of effectively reducing the risk and severity. 相似文献