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1.
Sarah Gilgunn Keefe Murphy Henning Stckmann Paul J. Conroy T. Brendan Murphy R. William Watson Richard J. OKennedy Pauline M. Rudd Radka Saldova 《International journal of molecular sciences》2020,21(23)
The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies. 相似文献
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GA Masters AM Mauer PC Hoffman D Wyka BL Samuels SA Krauss S Watson H Golomb EE Vokes 《Canadian Metallurgical Quarterly》1998,9(6):677-680
PURPOSE: We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. PATIENTS AND METHODS: We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. RESULTS: Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. CONCLUSIONS: This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents. 相似文献
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14 medicated hypertensive, 15 nonmedicated mild hypertensive, 39 normotensive, and 13 hypotensive adults participated in a 1–2 hr laboratory experiment that assessed each S's symptoms, moods, and estimates of systolic blood pressure (SBP) relative to actual SBP levels. Several self-reports and autonomic measures were collected during and after each of 22 tasks. Within-S correlations indicated that all Ss could estimate SBP at levels greater than chance. Further, 68% of the Ss evidenced at least 1 significant symptom–SBP correlation. Although medicated hypertensives believed they could estimate their BP more accurately than other groups, they were actually no more accurate than the other Ss. They also evidenced far fewer empirically derived symptom–SBP and emotion–SBP correlations than any other group. Overall, blood pressure (BP) beliefs were largely inaccurate. If these erroneous beliefs can be eliminated, Ss may be able to estimate BP fluctuations more accurately. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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For users of an executive information system (EIS), the EIS interface is the system and is crucial to the EIS's success. These guidelines for designing EIS interfaces are based on studies of actual EIS interfaces that meet the unique information needs of executives. 相似文献
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Many current implementations of protocols such as the Transmission Control Protocol/Internet Protocol (TCP/IP) are inefficient because data are often accessed more frequently than necessary. Three techniques that reduce the need for memory bandwidth are proposed. The techniques are copy-on-write, page remapping, and single-copy. Afterburner, a network-independent card that provides the services that are necessary for a single-copy protocol stack, is described. The card has 1 MByte of local buffers and provides a simple interface to a variety of network link adapters, including HIPPI and asynchronous transfer mode (ATM). Afterburner can support transfers to and from the link adapter card at rates up to 1 Gbit/s. An implementation of TCP/IP that uses the features provided by Afterburner to reduce the movement of data to a single copy is discussed. Measurements of the end-to-end performance of Afterburner and the single-copy implementation of TCP/IP are presented 相似文献
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JH Meador-Woodruff KY Little SP Damask A Mansour SJ Watson 《Canadian Metallurgical Quarterly》1993,34(6):348-355
The effects of chronic cocaine exposure on dopamine D1 and D2 receptor gene expression in the human brain were studied in postmortem samples from chronic cocaine abusing and matched control subjects. Using in situ hybridization of receptor autoradiography to examine messenger ribonucleic acid (RNA) and binding sites, respectively, neither D1 nor D2 receptor expression was found to be changed in the nucleus accumbens, caudate, putamen, or substantia nigra of the cocaine-exposed subjects. Although chronic cocaine exposure can produce alterations in dopaminergic neurotransmission, sustained compensatory changes in dopamine receptor expression do not appear to occur in the human. 相似文献
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FM Apter P Michetti LS Winner JA Mack JJ Mekalanos MR Neutra 《Canadian Metallurgical Quarterly》1993,61(12):5279-5285
Secretory immunoglobulin A (IgA) antibodies (sIgA) directed against cholera toxin (CT) and surface components of Vibrio cholerae are associated with protection against cholera, but the relative importance of specific sIgAs in protection is unknown. A monoclonal IgA directed against the V. cholerae lipopolysaccharide (LPS), secreted into the intestines of neonatal mice bearing hybridoma tumors, was previously shown to provide protection against a lethal oral dose of 10(7) V. cholerae cells. We show here that a single oral dose of 5 to 50 micrograms of the monoclonal anti-LPS IgA, given within 2 h before V. cholerae challenge, protected neonatal mice against challenge. In contrast, an oral dose of 80 micrograms of monoclonal IgA directed against CT B subunit (CTB) failed to protect against V. cholerae challenge. A total of 80 micrograms of monoclonal anti-CTB IgA given orally protected neonatal mice from a lethal (5-micrograms) oral dose of CT. Secretion of the same anti-CTB IgA antibodies into the intestines of mice bearing IgA hybridoma backpack tumors, however, failed to protect against lethal oral doses of either CT (5 micrograms) or V. cholerae (10(7) cells). Furthermore, monoclonal anti-CTB IgA, either delivered orally or secreted onto mucosal surfaces in mice bearing hybridoma tumors, did not significantly enhance protection over that provided by oral anti-LPS IgA alone. These results demonstrate that anti-LPS sIgA is much more effective than anti-CT IgA in prevention of V. cholerae-induced diarrheal disease. 相似文献