PubMed Health⌕ Search

Biomedical subjects

Jianhua Hu

Publications and source records attributed to Jianhua Hu.

10 recordsLinked to original sources

Profile of Ets gene expression in human breast carcinoma.

BACKGROUND: Ets genes encode a family of transcription factors that play key roles in cell proliferation, differentiation and apoptosis. Fusions of Ets genes with other targets have been described in Ewing's sarcoma, chronic myelomonocytic leukemia and more recently prostate carcinoma. Ets expression in breast carcinoma has not been comprehensively studied, and is the focus of this study. METHODS: RT-Q-PCR was used to determine the expression of Ets genes in a panel of ten common breast cancer cell lines, two immortalized normal breast epithelial cell lines, and one primary culture of human mammary epithelial cells. Ets with altered expression in cancer cell lines were verified in primary breast tumors. RESULTS: Transcripts of 21 of the 27 Ets genes were detected in either normal or cancer cells. Of the 21 detectable genes, 14 were expressed at a similar level in both normal and breast cancer cell lines. Four genes, Ehf, Elf3, Elf5 and Pdef, were expressed at higher levels in breast cancer cells than normal epithelials. Surprisingly, the expression of Elk3, Etsl and Flil was repressed in breast cancer cells. The protein status of Ehf, Elf3, Pdef, Elk3, Etsl and Flil, strongly correlated with the transcript data, suggesting that Ets expression is regulated primarily at the transcriptional level. Similarly, Elf3, Pdef and Tel2 were overexpressed, while Elk3, Etsl and Flil were under-expressed in primary breast tumor specimens in comparison with normal mammary tissues. CONCLUSIONS: Our study identified a subset of Ets genes with altered expression in breast carcinoma, implicating their roles in mammary tumorigenesis. While the Ets over-expression pattern is useful to uncover recurrent genetic alterations involving Ets genes, the repressed expression of several Ets genes suggests that some Ets proteins may play suppressor roles during breast cancer progression. Our results warrant detailed studies of individual Ets activity during mammary gland neoplasia.

Breast Neoplasms↗

Growth and characterization of highly branched nanostructures of magnetic nanoparticles.

Magnetite nanoparticles of Fe(3)O(4) have been found to grow into large highly branched nanostructures including nanochains and highly branched nanotrees in the solid state through a postannealing process. By varying the preparation conditions such as annealing time and temperature, the nanostructures could be easily manipulated. Changing the starting concentration of the magnetic nanoparticle solution also caused significant changes of the nanoarchitectures. When the magnetic nanoparticle concentration is low, the nanoparticles formed straight rods mainly with an average diameter of 80 nm and a length of several microns. With increasing concentration of the nanoparticles, treelike structures began to form. With further increase of the concentration, well-ordered nanostructures with the appearance of snowflakes were generated. The driving force for the formation of the highly ordered nanostructures includes interaction between the nanoparticles and interaction through surface-capping molecules. This experiment demonstrates that novel nanostructures can be generated by self-assembly of magnetic nanoparticles under the solid state.

Chemistry, Physical↗

Analysis of dose-response effects on gene expression data with comparison of two microarray platforms.

MOTIVATION: The problems of analyzing dose effects on gene expression are gaining attention in biomedical research. A specific challenge is to detect genes with expression levels that change according to dose levels in a non-random manner, but nonetheless may be considered as potential biomarkers. METHOD: We are among the first to formally apply a tool that uses an isotonic (monotonic) regression approach to this area of study. We introduce a test statistic to select genes with significant dose-response expression in a monotonic fashion based on a permutation procedure. We then compare the results with those achieved from the application of a likelihood ratio-based test. RESULTS: We apply the isotonic regression approach to a study of gene expression in the RKO colon carcinoma cell line in response to varying dosage levels of the chemotherapeutic agent 5-fluorouracil. A feature of both Affymetrix and printed 75mer oligomer cDNA arrays produced from the same samples provides an opportunity to compare the two microarray platforms. AVAILABILITY: Statistical software S-plus Code to implement the method is available from the authors. CONTACT: kcoombes@mdanderson.org

Algorithms↗

Practical FDR-based sample size calculations in microarray experiments.

MOTIVATION: Owing to the experimental cost and difficulty in obtaining biological materials, it is essential to consider appropriate sample sizes in microarray studies. With the growing use of the False Discovery Rate (FDR) in microarray analysis, an FDR-based sample size calculation is essential. METHOD: We describe an approach to explicitly connect the sample size to the FDR and the number of differentially expressed genes to be detected. The method fits parametric models for degree of differential expression using the Expectation-Maximization algorithm. RESULTS: The applicability of the method is illustrated with simulations and studies of a lung microarray dataset. We propose to use a small training set or published data from relevant biological settings to calculate the sample size of an experiment. AVAILABILITY: Code to implement the method in the statistical package R is available from the authors.

Algorithms↗

Chitosan nanoparticles as a novel delivery system for ammonium glycyrrhizinate.

The ammonium glycyrrhizinate-loaded chitosan nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP). The particle size and zeta potential of nanoparticles were determined, respectively, by dynamic light scattering (DLS) and a zeta potential analyzer. The effects, including chitosan molecular weight, chitosan concentration, ammonium glycyrrhizinate concentration and polyethylene glycol (PEG) on the physicochemical properties of the nanoparticles were studied. These nanoparticles have ammonium glycyrrhizinate loading efficiency. The encapsulation efficiency decreased with the increase of ammonium glycyrrhizinate concentration and chitosan concentration. The introduction of PEG can decrease significantly the positive charge of particle surface. These studies showed that chitosan can complex TPP to form stable cationic nanoparticles for subsequent ammonium glycyrrhizinate loading.

Chitosan↗

The importance of experimental design in proteomic mass spectrometry experiments: some cautionary tales.

Proteomic expression patterns derived from mass spectrometry have been put forward as potential biomarkers for the early diagnosis of cancer and other diseases. This approach has generated much excitement and has led to a large number of new experiments and vast amounts of new data. The data, derived at great expense, can have very little value if careful attention is not paid to the experimental design and analysis. Using examples from surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) and matrix-assisted laser desorption-ionisation/time-of-flight (MALDI-TOF) experiments, we describe several experimental design issues that can corrupt a dataset. Fortunately, the problems we identify can be avoided if attention is paid to potential sources of bias before the experiment is run. With an appropriate experimental design, proteomics technology can be a useful tool for discovering important information relating protein expression to disease.

Biomarkers, Tumor↗

Two simulation methods for constructing confidence bands under the additive risk model.

With right-censored failure time data, we propose procedures to construct simultaneous confidence bands for the survival curve of a given subject under the additive risk model. The distribution of the subject-specific cumulative hazard function can be approximated with a zero-mean Gaussian process, which can be generated through simulation methods. We propose two different simulation schemes to obtain the distribution of the supremum of the cumulative hazard process over the entire time range. The two simulation approaches are asymptotically equivalent, whereas the numerical forms are different. We construct two types of confidence bands, namely the equal precision band and the Hall-Wellner type band, through choosing suitable weight functions. Monte Carlo simulation studies show that both of the proposed confidence bands are appropriate for finite sample sizes. We illustrate the new proposal with a real example.

Computer Simulation↗

An efficient resampling method for assessing genome-wide statistical significance in mapping quantitative trait Loci.

Assessing genome-wide statistical significance is an important and difficult problem in multipoint linkage analysis. Due to multiple tests on the same genome, the usual pointwise significance level based on the chi-square approximation is inappropriate. Permutation is widely used to determine genome-wide significance. Theoretical approximations are available for simple experimental crosses. In this article, we propose a resampling procedure to assess the significance of genome-wide QTL mapping for experimental crosses. The proposed method is computationally much less intensive than the permutation procedure (in the order of 10(2) or higher) and is applicable to complex breeding designs and sophisticated genetic models that cannot be handled by the permutation and theoretical methods. The usefulness of the proposed method is demonstrated through simulation studies and an application to a Drosophila backcross.

Animals↗

Tracking of physical activity and aerobic power from childhood through adolescence.

PURPOSE: To evaluate the tracking of physical activity levels (PA) and aerobic power (VO2max) in African-American (AA) and Caucasian (CA) youth as they age from 8 to 16 yr. METHODS: Subjects were 529 girls and 535 boys for whom data were obtained at least three times over 7 yr and a subset of 387 girls and 404 boys who participated in all years. PA levels were obtained from a survey. VO2max was predicted from a cycle ergometer test. RESULTS: Spearman correlation for VO2max for years 1-7 for AA boys and girls were similar (rho approximately 0.53). Year 1-7 correlations for VO2max for the CA boys and girls were similar (rho approximately 0.50-0.53). The year 2-7 correlations for PA were similar for the AA and CA girls but higher for the AA than the CA boys. The kappa (kappa) statistics for VO2max indicated substantial year-to-year agreement on categorization (high, moderate, and low), with AA girls having the highest agreement and AA boys the lowest. The kappa statistic for high, moderate, and low PA groupings in girls of either ethnicity was quite low, whereas the kappa statistics for the boys were somewhat better. The general estimating equation (GEE) stability coefficients for tracking of VO2max were similar between the sexes and ethnicities (P<0.0001). The GEE stability coefficient for PA was better for the boys than girls and slightly better for the AA than CA. CONCLUSION: Although aerobic power and physical activity levels decline from childhood through adolescence, aerobic power tracks better than physical activity levels. Because tracking within the cohort is only moderate, change is possible if we intervene early in these youth.

Adolescent↗