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Biomedical subjects

Donna Berry

Publications and source records attributed to Donna Berry.

7 recordsLinked to original sources

Design and progress of a trial of selenium to prevent prostate cancer among men with high-grade prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia (HGPIN) is generally regarded as a premalignant lesion that progresses toward prostate cancer. In light of the significant sequelae of prostate cancer treatment, prevention is desirable, and men with HGPIN would be suitable, high-risk subjects. There is in vitro, in vivo, epidemiologic, and human experimental evidence that selenium supplementation may protect against prostate cancer. This article introduces the rationale for, and progress to date, of a double-blind, randomized, placebo-controlled trial of selenium supplementation (200 mug/d in the form of selenomethionine), to prevent the development of prostate cancer among men with HGPIN. The trial, Southwest Oncology Group Protocol 9917, funded by a National Cancer Institute program supporting pivotal prevention trials has registered 537 patients and has randomized >380 to date. Subject accrual is expected to be completed by the fall of 2006, with trial completion in 2009.

Adult↗

Authoring tools for web based surveys: A descriptive study.

Researchers utilizing web-based survey in their data collection have increased in the past decade. In parallel, the number of web-based survey tools offered by commercial vendors also have increased. This study was conducted to establish and define the critical success criteria for evaluation of a survey authoring tool and to review the top five most commonly used commercial tools.

Data Collection↗

Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer.

BACKGROUND: Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive androgen-independent prostate cancer. We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic, hormone-independent prostate cancer. METHODS: We randomly assigned 770 men to one of two treatments, each given in 21-day cycles: 280 mg of estramustine three times daily on days 1 through 5, 60 mg of docetaxel per square meter of body-surface area on day 2, and 60 mg of dexamethasone in three divided doses before docetaxel, or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily. The primary end point was overall survival; secondary end points were progression-free survival, objective response rates, and post-treatment declines of at least 50 percent in serum prostate-specific antigen (PSA) levels. RESULTS: Of 674 eligible patients, 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone. In an intention-to-treat analysis, the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone (17.5 months vs. 15.6 months, P=0.02 by the log-rank test), and the corresponding hazard ratio for death was 0.80 (95 percent confidence interval, 0.67 to 0.97). The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone (P<0.001 by the log-rank test). PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients, respectively (P<0.001), and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease, respectively (P=0.30). Grade 3 or 4 neutropenic fevers (P=0.01), nausea and vomiting (P<0.001), and cardiovascular events (P=0.001) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone. Pain relief was similar in both groups. CONCLUSIONS: The improvement in median survival of nearly two months with docetaxel and estramustine, as compared with mitoxantrone and prednisone, provides support for this approach in men with metastatic, androgen-independent prostate cancer.

Adenocarcinoma↗

Structural basis for specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition.

The SH3 domain, which normally recognizes proline-rich sequences, has the potential to bind motifs with an RxxK consensus. To explore this novel specificity, we have determined the solution structure of the Gads T cell adaptor C-terminal SH3 domain in complex with an RSTK-containing peptide, representing its physiological binding site on the SLP-76 docking protein. The SLP-76 peptide engages four distinct binding pockets on the surface of the Gads SH3 domain and upon binding adopts a unique structure characterized by a right-handed 3(10) helix at the RSTK locus, in contrast to the left-handed polyproline type II helix formed by canonical proline-rich SH3 ligands. The structure, and supporting mutagenesis and peptide binding data, reveal a novel mode of ligand recognition by SH3 domains.

Adaptor Proteins, Signal Transducing↗

Gads/Grb2-mediated association with LAT is critical for the inhibitory function of Gab2 in T cells.

A docking protein, Gab2, is recruited to the vicinity of the TCR complex and inhibits downstream signaling by interaction with negative regulators. However, the molecular mechanisms of this recruitment remain unclear. We have found that Gab2 associates with LAT upon TCR stimulation and that LAT is essential for Gab2 phosphorylation. By analysis of several Gab2 mutants, the c-Met binding domain (MBD) of Gab2 was found to be both necessary and sufficient for stimulation-induced LAT binding. Within the MBD domain, a novel Grb2 SH3 binding motif, PXXXR, is critical for constitutive association with Gads/Grb2. Through this association, Gab2 is recruited to the lipid raft after TCR ligation and exerts inhibitory function. The in vivo significance of this association is illustrated by the fact that T-cell responses are impaired in transgenic mice expressing wild-type Gab2 but not in mice expressing mutant Gab2 lacking the motif. Furthermore, T cells from Gab2-deficient mice showed enhanced proliferative responses upon TCR stimulation. These results indicate that Gads/Grb2-mediated LAT association is critical for the inhibitory function of Gab2, implying that Gab2 induced in stimulated T cells may exert an efficient negative feedback loop by recruiting inhibitory molecules to the lipid raft and competing with SLP-76 through Gads binding.

Adaptor Proteins, Signal Transducing↗

Psychometric testing of the translated McGill Quality of Life Questionnaire-Taiwan version in patients with terminal cancer.

BACKGROUND AND PURPOSE: Quality of life (QOL) is the paramount goal of end-of-life care. However, there is no Chinese language instrument for measuring QOL that has been shown to have adequate psychometric properties for Taiwanese patients with terminal cancer. The purpose of this study was to examine the psychometric properties of a Chinese language version of the McGill Quality of Life questionnaire (MQOL-Taiwan version) in this population. METHODS: The original English version of the MQOL questionnaire was translated into Chinese, and administered to 64 Taiwanese patients with terminal cancer for psychometric testing (factor structures and various types of reliability and validity). The cultural equivalence of the translation was tested by content validity index. Statistical analysis included exploratory factor analysis, Pearson's product moment correlation coefficient, and the calculation of Cronbach's alpha (alpha). RESULTS: Findings on the validity and reliability of the MQOL-Taiwan version were as follows. The value of content validity was 0.98. The range of the correlations between an item and its domain was 0.59 to 0.96 (all p < 0.05), and for inter-domain was 0.28 to 0.52 (all p < 0.05). The 4 domains of the original MQOL emerged as the 4 dominant factors (64% total variance explained) in the MQOL-Taiwan version, namely the domains of physical symptoms, psychological symptoms, existential well-being, and support. The internal consistency (Cronbach's alpha) coefficient of the whole MQOL-Taiwan version was 0.83, and those for the 4 domains ranged from 0.69 to 0.90. For the convergent and divergent validity, the MQOL-Taiwan version physical domain was moderately and significantly (r = -0.44, p < 0.05) correlated with the performance status rating of the Eastern Cooperative Oncology Group-Performance Status Rating (ECOG-PSR). The MQOL-Taiwan version psychological, existential, and support domains were not significantly correlated to the ECOG-PSR. CONCLUSIONS: The MQOL-Taiwan version demonstrated an acceptable level of reliability, validity and equivalency in the initial cross-cultural validation. These findings indicate the suitability of this QOL measure for clinical and research use in Taiwanese patients with terminal cancer.

Adult↗

Developing a computerized data collection and decision support system for cancer pain management.

Contemporary nursing practice needs reengineering to deliver its service effectively and efficiently. Using computer technology to support clinicians' decision making may be a parsimonious way to provide high-quality, patient-centered, efficient care. The process of developing the PAINReportIt and PAINConsultN system is described, and the results of two pilot studies in which the system was tested are summarized. The feasibility of using the system to assess pain and provide decision support for clinicians is demonstrated. The findings show PAINReportIt to be promising as an effective, efficient way for patients to report their pain. Whether PAINConsultN is an effective answer to cancer pain management barriers warrants further evaluation with larger samples. The advantages of using the system, as compared with use of the traditional pain management process, are discussed.

Decision Support Systems, Clinical↗