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61.
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
62.
Sandra Desa Souza Sujata H. Gadkari 《Indian journal of otolaryngology and head and neck surgery》1995,47(1):22-25
The literature on Neuroendocrine carcinoma of the nasal cavity and paranasal sinuses contains a plethora of contradictions concerning their nomenclature, classification, pathogenesis, diagnosis, therapy and prognosis. The term neuroendocrine carcinoma is used for malignant epithelial tumours showing a characteristic microscopic pattern and cytologic features. The idea of presenting this case of neuroendocrine malignancy, which itself is a very rare entity is to emphasise the role of electron microscopy in arriving at a diagnosis and the necessity of adequate surgical excision followed by radiotherapy for a longer tumour free survival. 相似文献
63.
The purpose of this study was to determine the accuracy of FirstTemp (Intelligent Medical Systems, Carlsbad, CA) tympanic thermometer readings compared with core body temperatures obtained via pulmonary artery catheter (PAC). Five measurements were obtained on 19 cardiovascular surgery patients. Tympanic thermometer measurements tended to be higher than PAC measurements. However, most of the differences were not clinically significant. Differences found between right and left ear measurements were most likely due to poor measurement technique. When the correct technique is used, nurses can be confident that tympanic temperature readings are clinically accurate. 相似文献
64.
Selecting antibodies to detect HER2 overexpression by immunohistochemistry in invasive mammary carcinomas. 总被引:1,自引:0,他引:1
Agostinho Pinto Gouvêa Fernanda Milanezi Sandra Jean Olson Dina Leitao Fernando Carlos Schmitt Helenice Gobbi 《Applied immunohistochemistry & molecular morphology》2006,14(1):103-108
There is an increasing clinical demand for HER2 analysis in breast cancer, especially since the release of trastuzumab. The authors assessed the ability of immunohistochemistry to detect HER2 overexpression in invasive mammary carcinomas (IMC) using five antibodies. Paraffin-embedded samples of 86 IMCs (T2N0) were used to compare the immunohistochemical overexpression of HER2 using two polyclonal antibodies (HercepTest [DAKO] and A0485 [DAKO]) and three monoclonal antibodies (CB11 from two different laboratories, Biogenex and Novocastra, and 4D5 [Genentech]). All immunostainings were scored according to the FDA-approved HercepTest recommendations. The HercepTest-positive cases were compared with gene amplification by FISH (Oncor Inform, Ventana). The HercepTest was positive in 31 of the 86 cases (36.1%). The DAKO antibody A0485 was positive in 25 of the 66 (37.8%). Monoclonal antibody 4D5 was positive in only 15 of the 86 cases (17.4%). There was almost total agreement in results between the two CB11 antibodies: 25 of the 86 positive cases (29.1%). All cases positive for CB11 or 4D5 were HercepTest positive. Most of the HercepTest 2+ cases were negative when using either monoclonal antibody. FISH was positive in 19 of the 20 HercepTest 3+ cases and negative in 5 HercepTest 2+ cases. Three CB11-2+ cases showed no amplification by FISH. In three FISH-positive cases the immunohistochemistry showed no overexpression by all antibodies used. These findings suggest that immunohistochemistry may be used reliably as a primary methodology for evaluating HER2; however, the use of polyclonal antibodies may not be adequate to assess HER2 overexpression. CB11, regardless of the manufacturer (Biogenex or Novocastra), showed better concordance with FISH (kappa=0.83) than did the polyclonal antibodies. 相似文献
65.
Jean-Pierre Lindenmayer M.D. Ruth Bernstein-Hyman Ph.D. Sandra Grochowski B.A. 《The Psychiatric quarterly》1994,65(4):299-322
Schizophrenic psychopathology is heterogeneous and multidimensional. Various strategies have been developed over the past
several years to assess and measure more accurately discrete domains of psychopathology. One of the more fruitful strategies
to investigate more homogenous domains of psychopathology has been the positive-negative syndrome approach. However, this
approach is unable to address a number of important issues. Most schizophrenics present a mixed syndrome; the criteria for
what constitutes a positive and negative syndrome are variable; distinguishing primary from secondary negative symptoms can
be difficult. In order to address some of these problems, we propose the introduction of a five syndrome model based on a
reanalysis of factor analytic procedures used on 240 schizophrenics assessed with the Positive and Negative Syndrome Scale
(PANSS). We present data on a 5-factor solution which appears to best fit the psychopathological data and which is supported
by three independent and comparable factor analyses; negative, positive, excitement, cognitive and depression/anxiety domains
of psychopathology give patients their individual mark. Data on internal consistency of the five factors and on initial validation
using demographic and clinical variables are presented. 相似文献
66.
Sandra Lobo Jaroslav Cervenka Arnold London Mary Ella M. Pierpont 《American journal of medical genetics. Part A》1992,43(4):701-703
We report on a patient with interstitial deletion of 10q and compare her to 8 previously described patients, 2 of whom have chromosomal breakpoints similar to our patient. Minor anomalies including broad forehead, hypertelorism, strabismus, prominent philtrum, and “dysplastic” pinnae are present in our patient. Psychomotor retardation and hypotonia are universal findings in 10q interstitial deletion. Growth retardation, not present in our patient, is seen in some. These clinical findings are sufficiently distinct to suggest early chromosome studies. © 1992 Wiley-Liss, Inc. 相似文献
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70.
S Sandra Carvalho-Bos Rixt F Riemersma-van der Lek Jim Waterhouse Thomas Reilly Eus J W Van Someren 《The American journal of geriatric psychiatry》2007,15(2):92-100
OBJECTIVE: The objective of this study is to investigate the association between actigraphic estimates of the sleep-wake rhythm and a range of functional domains that contribute to well-being in demented elderly patients. METHOD: Eighty-seven women aged 85.5 +/- 5.9 years (mean +/- standard deviation) wore an actigraph for two weeks. Activity profiles were analyzed using nonparametric variables, including dichotomy indices, interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA). The associations between these variables and cognitive, functional, behavioral, and emotional states (obtained from standardized neuropsychologic assessments and questionnaires administered to caregivers) were investigated by partial correlations and stepwise regressions. RESULTS: Cognitive, functional, behavioral, and emotional states showed medium to strong correlations with multiple rhythm variables. Partial correlations indicated that this could not be attributed to a uniform worsening with advancing cognitive decline. Stepwise regressions indicated three most distinctive rhythm variables: 1) the interdaily stability of the 24-hour rhythm was most strongly, negatively, related to cognitive decline and depression; 2) the median level of daytime activity was most strongly, negatively, related to impairments of function, of activities of daily living, and of social interaction; and 3) nocturnal restlessness was secondarily, positively, related to impairments of function and social interaction. CONCLUSION: Especially the interdaily stability and median daytime activity level, and secondarily nocturnal restlessness, showed a strong relationship with the functional status and well-being of demented elderly. This raises the possibility that treatments that enhance daytime activity and the stability of the rest-activity rhythm may improve well-being. 相似文献