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Jose Costa

Publications and source records attributed to Jose Costa.

9 recordsLinked to original sources
PubMed2007

Technology insight: will systems pathology replace the pathologist?

By using systems pathology, it might be possible to provide a predictive, personalized therapeutic recommendation for patients with prostate cancer. Systems pathology integrates quantitative data and information from many sources to generate a reliable prediction of the expected natural course of the disease and response to different therapeutic options. In other words, through the integration of relatively large data sets and the use of knowledge engineering, systems pathology aims at predicting the future behavior of tumors and their interaction with the host. In this Review, we introduce the methods used in systems pathology and summarize a recent study providing the first evidence of a concept for this strategy. The results show that systems pathology can provide a personalized prediction of the risk of recurrence after prostatectomy for cancer.

Humans↗
PubMed2005

Carotenoid, tocopherol, phenolic acid, and antioxidant properties of Maryland-grown soft wheat.

Consumers' desires to either reduce the risk of or manage a specific health condition through improved diet have stimulated the research of agricultural products for their potential health beneficial components such as tocopherols and natural antioxidants. Soft wheat is one of the major crops in Maryland, with little information available about its potentially beneficial components. This study examined eight selected Maryland-grown soft wheat varieties or experimental lines for their potential beneficial components including tocopherols, carotenoids, total phenolics and phenolic acids and their antioxidant properties, including Fe(2+) chelating capacity and free radical scavenging activities against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(*) ), radical cation ABTS(*)(+), and oxygen radical (ORAC). The results showed that all tested soft wheat grain samples contained alpha-tocopherol, with a range of 3.4-10.1 microg/g. Lutein was the primary carotenoid present in the grain samples at a level of 0.82-1.14 microg/g, along with significant amounts of zeaxanthin and beta-carotene. Vanillic, syringic, p-coumaric, and ferulic acids were found in soluble free, soluble conjugated, and insoluble bound forms in the grain extracts, with ferulic acid as the predominant phenolic acid. The eight soft wheat varieties differed in their antioxidant properties. The tested wheat grain samples exhibited ED(50) values against DPPH(*) of 23-27 mg of grain equiv/mL, ORAC of 32.9-48 micromol of Trolox equiv (TE)/g, and ABTS(*)(+) scavenging capacity of 14.3-17.6 micromol of TE/g. These data suggest the possibility of producing soft wheat varieties rich in selected health beneficial factors for optimum human nutrition though breeding programs.

Antioxidants↗
PubMed2005

Optimized normalization for antibody microarrays and application to serum-protein profiling.

The measurements of coordinated patterns of protein abundance using antibody microarrays could be used to gain insight into disease biology and to probe the use of combinations of proteins for disease classification. The correct use and interpretation of antibody microarray data requires proper normalization of the data, which has not yet been systematically studied. Therefore we undertook a study to determine the optimal normalization of data from antibody microarray profiling of proteins in human serum specimens. Forty-three serum samples collected from patients with pancreatic cancer and from control subjects were probed in triplicate on microarrays containing 48 different antibodies, using a direct labeling, two-color comparative fluorescence detection format. Seven different normalization methods representing major classes of normalization for antibody microarray data were compared by their effects on reproducibility, accuracy, and trends in the data set. Normalization with ELISA-determined concentrations of IgM resulted in the most accurate, reproducible, and reliable data. The other normalization methods were deficient in at least one of the criteria. Multiparametric classification of the samples based on the combined measurement of seven of the proteins demonstrated the potential for increased classification accuracy compared with the use of individual measurements. This study establishes reliable normalization for antibody microarray data, criteria for assessing normalization performance, and the capability of antibody microarrays for serum-protein profiling and multiparametric sample classification.

Adenocarcinoma↗
PubMed2004

Two-color, rolling-circle amplification on antibody microarrays for sensitive, multiplexed serum-protein measurements.

The ability to conveniently and rapidly profile a diverse set of proteins has valuable applications. In a step toward further enabling such a capability, we developed the use of rolling-circle amplification (RCA) to measure the relative levels of proteins from two serum samples, labeled with biotin and digoxigenin, respectively, that have been captured on antibody microarrays. Two-color RCA produced fluorescence up to 30-fold higher than direct-labeling and indirect-detection methods using antibody microarrays prepared on both polyacrylamide-based hydrogels and nitrocellulose. Replicate RCA measurements of multiple proteins from sets of 24 serum samples were highly reproducible and accurate. In addition, RCA enabled reproducible measurements of distinct expression profiles from lower-abundance proteins that were not measurable using the other detection methods. Two-color RCA on antibody microarrays should allow the convenient acquisition of expression profiles from a great diversity of proteins for a variety of applications.

Antibodies↗
PubMed2004

Somatic D-loop mitochondrial DNA mutations are frequent in uterine serous carcinoma.

The mitochondria plays a role in apoptosis. Its genome is also more susceptible to mutations because of high levels of reactive oxygen species and limited repair mechanisms. The D-loop of mitochondrial DNA (mtDNA) contains essential transcription and replication elements, and mutations in this region might alter the rate of DNA replication. We examined genetic alterations in the D-loop region of mtDNA in uterine serous carcinoma (USC) samples and their paired normal adjacent endometrium. DNA was extracted after laser-capture microdissection of paraffin-embedded tissues from eight patients with USC. The entire D-loop genome was amplified using nine pairs of overlapping primers. Denatured polymerase chain reaction (PCR) products were subjected to single-strand conformation polymorphism (SSCP) analysis. Somatic mtDNA alterations were detected in five tumours (63%). Our study indicates that mtDNA D-loop sequence alterations occur at a high frequency in USC suggesting that mtDNA mutations may play a role in the development of USC.

Aged↗
PubMed2003

ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer.

PURPOSE: ras oncogenic activation has long been demonstrated in thyroid carcinomas of follicular cell derivation, but no consistent relationship has been shown between mutations and clinicopathologic features. MATERIALS AND METHODS: We analyzed H-, K-, and N-ras mutations by polymerase chain reaction-single-strand conformational polymorphism followed by DNA sequencing in 125 thyroid carcinoma specimens from 107 patients, to include tumors covering the entire spectrum of thyroid tumor differentiation. RESULTS: Mutations were identified in four (8.2%) of 49 well-differentiated carcinomas (WDCs; two [6.7%] of 30 of the tumors were papillary carcinomas, two [10.5%] of 19 of them were follicular carcinomas), in 16 (55.2%) of 29 poorly differentiated carcinomas (PDCs), and in 15 (51.7%) of 29 undifferentiated carcinomas, with a significant association between ras mutation and poorly or undifferentiated tumors (P <.001). Twenty-six (74.3%) of 35 patients with ras-mutated tumors died as a result of disease as opposed to 23 (31.9%) of 72 patients with tumors lacking the mutations. Among patients with differentiated thyroid carcinomas (WDC and PDC), 11 (55.0%) of 20 patients with mutated tumors died as a result of disease as opposed to nine (15.5%) of 58 patients with wild-type ras tumors, and the correlation was independent of tumor differentiation and stage (P =.016). K-ras codon 13 mutations (all with G-A nucleotide transitions resulting in Gly>Asp substitution) and single activating mutations in any of the ras genes were also independent predictors of poor survival in differentiated thyroid carcinomas (P =.027 and P =.007, respectively). CONCLUSION: These findings demonstrate that ras mutations are a marker for aggressive cancer behavior and indicate a possible role of ras genotyping to identify thyroid carcinoma subsets associated with poor prognosis.

Carcinoma, Papillary, Follicular↗
PubMed2003

Whole genome analysis of genetic alterations in small DNA samples using hyperbranched strand displacement amplification and array-CGH.

Structural genetic alterations in cancer often involve gene loss or gene amplification. With the advent of microarray approaches for the analysis of the genome, as exemplified by array-CGH (Comparative Genomic Hybridization), scanning for gene-dosage alterations is limited only by issues of DNA microarray density. However, samples of interest to the pathologist often comprise small clusters of just a few hundred cells, which do not provide sufficient DNA for array-CGH analysis. We sought to develop a simple method that would permit amplification of the whole genome without the use of thermocycling or ligation of DNA adaptors, because such a method would lend itself to the automated processing of a large number of tissue samples. We describe a method that permits the isothermal amplification of genomic DNA with high fidelity and limited sequence representation bias. The method is based on strand displacement reactions that propagate by a hyperbranching mechanism, and generate hundreds, or even thousands, of copies of the genome in a few hours. Using whole genome isothermal amplification, in combination with comparative genomic hybridization on cDNA microarrays, we demonstrate the ability to detect gene losses in yeast and gene dosage imbalances in human breast tumor cell lines. Although sequence representation bias in the amplified DNA presents potential problems for CGH analysis, these problems have been overcome by using amplified DNA in both control and tester samples. Gene-dosage alterations of threefold or more can be observed with high reproducibility with as few as 1000 cells of starting material.

Breast Neoplasms↗