No-match ORESTES explored as tumor markers.

Sequencing technologies and new bioinformatics tools have led to the complete sequencing of various genomes. However, information regarding the human transcriptome and its annotation is yet to be completed. The Human Cancer Genome Project, using ORESTES (open reading frame EST sequences) methodology, contributed to this objective by generating data from about 1.2 million expressed sequence tags. Approximately 30% of these sequences did not align to ESTs in the public databases and were considered no-match ORESTES. On the basis that a set of these ESTs could represent new transcripts, we constructed a cDNA microarray. This platform was used to hybridize against 12 different normal or tumor tissues. We identified 3421 transcribed regions not associated with annotated transcripts, representing 83.3% of the platform. The total number of differentially expressed sequences was 1007. Also, 28% of analyzed sequences could represent noncoding RNAs. Our data reinforces the knowledge of the human genome being pervasively transcribed, and point out molecular marker candidates for different cancers. To reinforce our data, we confirmed, by real-time PCR, the differential expression of three out of eight potentially tumor markers in prostate tissues. Lists of 1007 differentially expressed sequences, and the 291 potentially noncoding tumor markers were provided.

Benefits in radical mastectomy protocol: a randomized trial evaluating the use of regional anesthesia.

Surgery is the first-line treatment for early, localized, or operable breast cancer. Regional anesthesia during mastectomy may offer the prevention of postoperative pain. One potential protocol is the combination of serratus anterior plane block (SAM block) with pectoral nerve block I (PECS I), but the results and potential benefits are limited. Our study compared general anesthesia with or without SAM block + PECS I during radical mastectomy with axillary node dissection and breast reconstruction using evaluations of pain, opioid consumption, side effects and serum levels of interleukin (IL)-1beta, IL-6 and IL-10. This is a prospective, randomized controlled trial. Fifty patients were randomized to general anesthesia only or general anesthesia associated with SAM block + PECS I (25 per group). The association of SAM block + PECS I with general anesthesia reduced intraoperative fentanyl consumption, morphine use and visual analog pain scale scores in the post-anesthetic care unit (PACU) and at 24 h after surgery. In addition, the anesthetic protocol decreased side effects and sedation 24 h after surgery compared to patients who underwent general anesthesia only. IL-6 levels increased after the surgery compared to baseline levels in both groups, and no differences in IL-10 and IL-1 beta levels were observed. Our protocol improved the outcomes of mastectomy, which highlight the importance of improving mastectomy protocols and focusing on the benefits of regional anesthesia.

Identification and characterization of a novel mouse gene encoding a Ras-associated guanine nucleotide exchange factor: expression in macrophages and myocarditis elicited by Trypanosoma cruzi parasites.

The ability of Trypanosoma cruzi to activate macrophages is, at least in part, attributed to the glycosylphosphatidylinositol-anchored mucin-like glycoproteins (GPI-mucins) expressed in the surface of the trypomastigote stage of the parasite. The differential display reverse transcriptase-polymerase chain reaction and the reverse Northern blot were used to study modulation of gene expression in murine macrophages exposed to GPI-mucins and in cardiac tissues from mice infected with T. cruzi. Among several cDNAs that were more abundant in lanes corresponding to macrophages stimulated with GPI-mucins as compared with resting cells, we confirmed the differential expression of A1, interleukin-18, and GPIgamma4. Some of these genes were also shown to have enhanced expression in the cardiac tissue (DAP-12, A1, and GPIgamma4) from infected animals. The expression of GPIgamma4 was also enhanced in human monocytes stimulated with GPI-mucins or bacterial lipopolysaccharides. The complete sequence of the GPIgamma4 transcript and its gene including the 5' upstream region was defined. GPIgamma4 was encoded by a novel, single copy gene present in mouse as well as human genomes and showed conserved homology to different members of the guanine nucleotide exchange factor family.