Biomedical subjects

Aiyi Liu

Publications and source records attributed to Aiyi Liu.

8 recordsLinked to original sources

PubMed2003

Group sequential design for comparative diagnostic accuracy studies.

In the field of diagnostic medicine, comparative clinical trials are necessary for assessing the utility of one diagnostic test over another. The area under the receiver operating characteristic (ROC) curve, commonly referred to as AUC, is a general measure of a test's inherent ability to distinguish between patients with and without a condition. Standardized AUC difference is the most frequently used statistic for comparing two diagnostic tests. In therapeutic comparative clinical trials with sequential patient entry, fixed sample design (FSD) is unjustified on ethical and economical grounds and group sequential design (GSD) is frequently used. In this paper, we argue that the same reasoning exists for the comparative clinical trials in diagnostic medicine and hence GSD should be utilized in this field for designing trials. Since computation of the stopping boundaries of GSD and data analysis after a group sequential test rely heavily on Brownian motion approximation, we derive the asymptotic distribution of the standardized AUC difference statistic and point out its resemblance to the Brownian motion. Boundary determination and sample size calculation are then illustrated through an example from a cancer clinical trial.

Area Under Curve↗

PubMed2002

Block principal component analysis with application to gene microarray data classification.

We propose a block principal component analysis method for extracting information from a database with a large number of variables and a relatively small number of subjects, such as a microarray gene expression database. This new procedure has the advantage of computational simplicity, and theory and numerical results demonstrate it to be as efficient as the ordinary principal component analysis when used for dimension reduction, variable selection and data visualization and classification. The method is illustrated with the well-known National Cancer Institute database of 60 human cancer cell lines data (NCI60) of gene microarray expressions, in the context of classification of cancer cell lines.

DNA, Neoplasm↗

PubMed2002

Mediating mechanisms for the impact of bupropion in smoking cessation treatment.

Several studies have documented the effectiveness of bupropion for smoking cessation, yet little is known about the mechanisms by which it facilitates abstinence. In this placebo-controlled randomized trial. We examined whether bupropion's effects on cessation were mediated by changes in withdrawal and/or negative or positive affect (PA). Two hundred and fifty-one smokers received 10-week treatment with bupropion or placebo, plus behavioral counseling. Changes in affect and withdrawal symptoms from pre-quit to 1 week post quit were examined as mediating variables in structural equation models. Cotinine-verified 7-day point prevalence cessation rates at the end of treatment (8-weeks post quit date) were 48% for bupropion and 29% for placebo (P=0.001). There were significant treatment effects on withdrawal and negative affect (NA); however, only change in NA predicted cessation. In a path model, change in NA was a significant mediator of bupropion's effects on cessation. However, the proportion of variance accounted for by this mediator was small, suggesting that other unmeasured factors play an important role. Laboratory-based paradigms may be useful to identify other mediators of bupropion's effects, thereby pointing to mechanisms of effect that can be bolstered in future treatment studies.

Adult↗

PubMed2002

Sample size and power determination for clustered repeated measurements.

It is common in epidemiological and clinical studies that each subject has repeated measurements on a single common variable, while the subjects are also 'clustered'. To compute sample size or power of a test, we have to consider two types of correlation: correlation among repeated measurements within the same subject, and correlation among subjects in the same cluster. We develop, based on generalized estimating equations, procedures for computing sample size and power with clustered repeated measurements. Explicit formulae are derived for comparing two means, two slopes and two proportions, under several simple correlation structures.

Alveolar Bone Loss↗

PubMed2002

Association of interferon regulatory factor-1, nucleophosmin, nuclear factor-kappaB, and cyclic AMP response element binding with acquired resistance to Faslodex (ICI 182,780).

To identify genes associated with survival from antiestrogens, both serial analysis of geneexpression and gene expression microarrays were used to explore the transcriptomes of antiestrogen-responsive (MCF7/LCC1) and -resistant variants(MCF7/LCC9) of the MCF-7 human breast cancer cell line. Structure of the gene microarray expression data was visualized at the top level using a novel algorithm that derives the first three principal components,fitted to the antiestrogen-resistant and -responsive gene expression data, from Fisher's information matrix. The differential regulation of several candidate genes was confirmed. Functional studies of the basal expression and endocrine regulation of transcriptional activation of implicated transcription factors were studied using promoter-reporter assays. The putative tumor suppressor interferon regulatory factor-1 is down-regulated in resistant cells, whereas its nucleolar phosphoprotein inhibitor nucleophosmin is up-regulated. Resistant cells also up-regulate the transcriptional activation of cyclic AMP response element (CRE) binding and nuclear factor kappaB (NFkappaB) while down-regulating epidermal growth factor receptor protein expression. Inhibition of NFkappaB activity by ICI 182,780 is lost in resistant cells, but CRE activity is not regulated by ICI 182,780 in either responsive or resistant cells. Parthenolide, a potent and specific inhibitor of NFkappaB, inhibits the anchorage-dependent proliferation of antiestrogen-resistant but not antiestrogen-responsive cells. This observation implies a greater reliance on their increased NFkappaB signaling for proliferation in cells that have survived prolonged exposure to ICI 182,780. These data from serial analysis of gene expression and gene microarray studies implicate changes in a novel signaling pathway, involving interferon regulatory factor-1, nucleophosmin, NFkappaB, and CRE binding in cell survival after antiestrogen exposure. Cells can up-regulate some estrogen-responsive genes while concurrently losing the ability of antiestrogens to regulate their expression. Signaling pathways that are not regulated by estrogens also can be up-regulated. Thus, some breast cancer cells may survive antiestrogen treatment by bypassing specific growth inhibitory signals induced by antagonist-occupied estrogen receptors.

Animals↗

PubMed2002

Estrogen receptor beta splice variant mRNAs are differentially altered during breast carcinogenesis.

We previously identified 10 exon deletion ERbeta variant mRNAs in various human tissues [FEBS Lett. 516 (2002) 133]. In the current study, we have investigated the expression of these variant mRNAs in normal breast tissues and their alterations in cancer tissues. A total of 43 cancer tissues in comparison with their matched normal tissues were analyzed by RT PCR using the newly developed 'Splice Targeted Primer Approach'. The data presented here show that normal breast tissues express 9 of the 10 identified variant mRNAs. Of the nine variants, the mRNAs with exons 5-6 deletions were significantly decreased ( approximately 80%) in a large majority of cancer tissues (two-sided paired t-test, n=43 patients, P<0.00001). The expression of ERbeta exon 5Delta, that could potentially have transactivating property in the absence of hormone, was changed differently among different grade tumors (analysis of variance F-test, n=43 patients, P=0.0452; Kruskal-Wallis test, n=43 patients, P=0.0356). When change in expression of ERbeta exon 5Delta mRNA levels was used as a categorical variable, a significant association was found between the change status (increase, no change, decrease) of this variant and grade of the tumor (Fischer's exact test, n=43 patients, P=0.0129). In particular, it was significantly increased in grade III tumors and decreased in grade II tumors. This variant was also changed differently in pre- and post-menopausal women. Its expression levels were increased in the tumors of post-menopausal women (mean change=3.6685), while they were decreased in pre-menopausal women (mean change=-24.3662). Thus a significant association was observed between the expression of this variant and menopausal status (a two-sided paired t-test, n=43 patients, P=0.03). Other variants were either expressed at very low frequency or not significantly altered.

Adult↗

PubMed2002

Development and validation of a method for using breast core needle biopsies for gene expression microarray analyses.

PURPOSE: Gene expression microarray technologies have the potential to define molecular profiles that may identify specific phenotypes(diagnosis), establish a patient's expected clinical outcome (prognosis), and indicate the likelihood of a beneficial effect of a specific therapy (prediction). We wished to develop optimal tissue acquisition, processing, and analysis procedures for exploring the gene expression profiles of breast core needle biopsies representing cancer and noncancer tissues. EXPERIMENTAL DESIGN: Human breast cancer xenografts were used to evaluate several processing methods for prospectively collecting adequate amounts of high-quality RNA for gene expression microarray studies. Samples were assessed for the preservation of tissue architecture and the quality and quantity of RNA recovered. An optimized protocol was applied to a small study of core needle breast biopsies from patients, in which we compared the molecular profiles from cancer with those from noncancer biopsies. Gene expression data were obtained using Research Genetics, Inc. Named Genes cDNA microarrays. Data were visualized using simple hierarchical clustering and a novel principal component analysis-based multidimensional scaling. Data dimensionality was reduced by simple statistical approaches. Predictive neural networks were built using a multilayer perceptron and evaluated in an independent data set from snap-frozen mastectomy specimens. RESULTS: Processing tissue through RNALater preserves tissue architecture when biopsies are washed for 5 min on ice with ice-cold PBS before histopathological analysis. Cell margins are clear, tissue folding and fragmentation are not observed, and integrity of the cores is maintained, allowing optimal pathological interpretation and preservation of important diagnostic information. Adequate concentrations of high-quality RNA are recovered; 51 of 55 biopsies produced a median of 1.34 microg of total RNA (range, 100 ng to 12.60 microg). Snap-freezing or the use of RNALater does not affect RNA recovery or the molecular profiles obtained from biopsies. The neural network predictors accurately discriminate between predominantly cancer and noncancer breast biopsies. CONCLUSIONS: The approaches generated in these studies provide a simple, safe, and effective method for prospectively acquiring and processing breast core needle biopsies for gene expression studies. Gene expression data from these studies can be used to build accurate predictive models that separate different molecular profiles. The data establish the use and effectiveness of these approaches for future prospective studies.

Animals↗

PubMedDate not supplied

Intergenerational transmission of pathogenic heteroplasmic mitochondrial DNA.

PURPOSE: To study the pattern of intergenerational transmission of pathogenic mitochondrial DNA with heteroplasmic A3243G, G8363A, A8344G, T8993G, and T8993C mutations. METHODS: The mutant load in the carrier mother and her offspring was measured in a total of 79 transmissions. Statistical analysis was performed to determine whether the intergenerational change in heteroplasmic mutant mtDNA is significant. RESULTS: Our results demonstrate that A3243G and T8993G mutant mtDNAs are significantly increased in blood, hair follicles, and buccal mucosal cells, during intergenerational transmission, whereas the intergenerational increase in T8993C and A8363G mutant mtDNA is not significant. Unlike previous reports, in one large family with A8344G mutation, the mutant load was slightly increased, instead of decreased, during transmission. There is no significant difference in the intergeneration transmission of mutant mtDNA to male or female offspring. CONCLUSION: Intergenerational transmission of heteroplasmic A3243G and T8993G mtDNA results in significant increase of mutant mtDNA in the offspring. Transmission of T8993C, G8363A, and A8344G does not result in significant intergenerational change in mutant load. Tissue specificity and genetic background may play important roles in the transmission of pathogenic heteroplasmic mtDNA.

DNA Mutational Analysis↗