Biomedical subjects

Darue A Prieto

Publications and source records attributed to Darue A Prieto.

3 recordsLinked to original sources

PubMed2006

Increased serum levels of complement C3a anaphylatoxin indicate the presence of colorectal tumors.

BACKGROUND & AIMS: Late diagnosis of colorectal carcinoma results in a significant reduction of average survival times. Yet despite screening programs, about 70% of tumors are detected at advanced stages (International Union Against Cancer stages III/IV). We explored whether detection of malignant disease would be possible through identification of tumor-specific protein biomarkers in serum samples. METHODS: A discovery set of sera from patients with colorectal malignancy (n = 58) and healthy control individuals (n = 32) were screened for potential differences using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Candidate proteins were identified and their expression levels were validated in independent sample sets using a specific immunoassay (enzyme-linked immunosorbent assay). RESULTS: By using class comparison and custom-developed algorithms we identified several m/z values that were expressed differentially between the malignant samples and the healthy controls of the discovery set. Characterization of the most prominent m/z values revealed a member of the complement system, the stable form of C3a anaphylatoxin (ie, C3a-desArg). Based on a specific enzyme-linked immunosorbent assay, serum levels of complement C3a-desArg predicted the presence of colorectal malignancy in a blinded validation set (n = 59) with a sensitivity of 96.8% and a specificity of 96.2%. Increased serum levels were also detected in 86.1% of independently collected sera from patients with colorectal adenomas (n = 36), whereas only 5.6% were classified as normal. CONCLUSIONS: Complement C3a-desArg is present at significantly higher levels in serum from patients with colorectal adenomas (P < .0001) and carcinomas (P < .0001) than in healthy individuals. This suggests that quantification of C3a-desArg levels could ameliorate existing screening tests for colorectal cancer.

Adenoma↗

PubMed2004

Proteomic patterns for early cancer detection.

The advent of proteomics has brought with it the hope of discovering novel biomarkers that can be used to diagnose diseases, predict susceptibility, and monitor progression. Much of this effort has focused on the mass spectral identification of the thousands of proteins that populate complex biosystems such as serum and tissues. A revolutionary approach in proteomic pattern analysis has emerged as an effective method for the early diagnosis of diseases such as ovarian, breast, and prostate cancer. This technology is capable of analyzing hundreds of clinical samples per day and has the potential to be a novel, highly sensitive diagnostic tool for the early detection of diseases, or as a predictor of response to therapy.

Biomarkers, Tumor↗

PubMed2002

Increased peripheral expansion of naive CD4+ T cells in vivo after IL-2 treatment of patients with HIV infection.

Intermittent interleukin-2 (IL-2) therapy has been shown to increase the number of CD4+ T cells, preferentially cells with a naive phenotype, in patients with HIV infection. For this report we investigated the mechanism underlying this expansion by studying the relative roles of peripheral expansion and thymic output. In a cohort of six patients receiving IL-2 over a period of 1 year, the mean number of naive CD4+ T cells increased from 139 to 387 cells per microl while levels of T cell receptor rearrangement excision circles (TRECs) declined from 47,946 to 26,510 copies per 10(6) naive T cells, thus making it unlikely that the CD4+ T cell count increases were secondary to increase in thymic output. To examine directly the impact of IL-2 on peripheral expansion, peripheral blood mature, naive CD4+ T cells were labeled ex vivo with 5-bromodeoxyuridine as well as stained directly for Ki67. These studies revealed a 7-fold increase in the percentage of 5-bromodeoxyuridine-positive cells and a 20-40-fold increase in Ki67 staining in the naive CD4+ T cell pool in the setting of IL-2 administration. This degree of increase in mature CD4+ T cell turnover induced by IL-2 does not compromise the future replicative potential of these cells, because longitudinal measurements of telomere length went from 6,981 to 7,153 bp after 1 year of IL-2 therapy. These data strongly suggest that much of the increase in CD4+ cells associated with IL-2 treatment is caused by peripheral expansion of existing naive CD4+ T cells rather than increased thymic output and that these increases occur without compromising the potential of these cells for further cell division.

Adult↗