Biomedical subjects

Fabrício F Costa

Publications and source records attributed to Fabrício F Costa.

6 recordsLinked to original sources

PubMed2006

Concise review: cancer/testis antigens, stem cells, and cancer.

In the multistep process of cancer development, the concept that cancer stem cells are derived from normal stem cells that have gradually accumulated various genetic and epigenetic defects is gaining strong evidence. A number of investigations have identified molecular markers that, under normal conditions, are responsible for stem cell homeostasis but are also expressed in tumor "stem cell-like" subpopulations. In this regard, it was recently reported that a group of tumor-specific antigens known as cancer/testis antigens (CTAs) are expressed in human MSCs. It has long been stated that in normal tissue these antigens are exclusively expressed in germ cell precursors; however, based on these results, we suggest that CTAs are expressed at earlier stages during embryogenesis. The tumor-restricted expression of CTAs has led to several immunotherapeutic trials targeting some of these proteins. The clinical implications that these trials may have on the normal stem cell pools, as well as the immunologic properties of these cells, is to date poorly studied and should be considered.

Antigens, Neoplasm↗

PubMed2006

Non-coding RNAs: lost in translation?

In the last ten years, several RNAs with no protein-coding potential have been accumulating in RNA databases and are in need of further molecular characterization. At the same time, examples of non-coding RNAs (ncRNAs) such as microRNAs, small RNAs, small interfering RNAs (siRNAs) and medium/large RNAs with various functions have been described in the literature. Recent evidence points to a widespread role of these molecules in eukaryotic cells, suggesting that the majority of the new ncRNA examples might have specific functions. The aim of this review is to describe several new functional ncRNAs that have been recently identified and characterized, providing some clues that these molecules might not be produced by chance or as by-products of transcription as has been speculated.

Animals↗

PubMed2006

SATR-1 hypomethylation is a common and early event in breast cancer.

Genome stability and normal gene expression are maintained by a fixed and predetermined DNA methylation pattern, which becomes abnormal in malignant cells. Hypomethylation of satellite DNA sequences is frequently found in tumors and has been associated with an increased frequency of DNA rearrangements and chromosome instability. In this work, we used methylation-sensitive arbitrarily primed polymerase chain reaction (MSAP-PCR) to identify differentially methylated DNA fragments in normal and tumor breast samples. We identified a novel differentially methylated fragment located on chromosome 5 with high similarity to a SATR-1 satellite sequence. This fragment was found to be hypomethylated in 63% of breast tumor cell lines and in 86% of breast tumors relative to normal breast tissue. We found that normal tissue adjacent to breast tumors displayed a variable decrease in methylation and that the decrease observed for most of these adjacent samples was higher than observed for normal breast tissue derived from reduction mammoplasty. The methylation decrease was, however, significantly higher in tumor samples than in adjacent tissue (chi2= 154, 1 df, P < 10(-4)), suggesting that SATR-1 hypomethylation frequently occurs in the early stages of tumor development. Our results highlight the importance of global DNA hypomethylation as a contributing factor in breast tumorigenesis.

Base Sequence↗

PubMed2005

Non-coding RNAs: new players in eukaryotic biology.

The completion of the human, mouse and other eukaryotic genomes were important scientific milestones, but they were just small steps towards the understanding of eukaryotic biology. Recent transcriptome analysis and different experimental approaches have identified a surprisingly large number of non-coding RNAs (ncRNAs) in eukaryotic cells. ncRNAs comprise microRNAs, anti-sense transcripts and other Transcriptional Units containing a high density of stop codons and lacking any extensive "Open Reading Frame". They have been shown to regulate gene expression by novel mechanisms such as RNA interference, gene co-suppression, gene silencing, imprinting and DNA demethylation. It is becoming clear that these novel RNAs perform critical functions during development and cell differentiation. There is also mounting evidence of their involvement in cancer and neurological diseases. Together, all this information indicates that ncRNAs are emerging as a new class of functional transcripts in eukaryotes. Therefore, great challenges lie in the years ahead: understanding the molecular biology of higher organisms will require revealing all proteins (Proteome), all ncRNAs (RNome) and their interactions (Interactome) in the complex molecular scenario within eukaryotic cells.

Animals↗

PubMed2005

ADAM23 methylation and expression analysis in brain tumors.

The ADAMs comprises a family of cell surface proteins with putative roles in cell-cell and/or cell-matrix interactions and in protease activities. In this work, we have examined the expression level and the methylation status of the 5' upstream region of the adhesion molecule ADAM23 in two brain tumor cell lines (A172 and T98G) as well as in three primary brain tumors (one grade II astrocytoma and two meningiomas) and 15 glioblastoma xenografts. Using bisulfite sequencing we verified that the percentage of methylated dinucleotides is higher in T98G when compared to A172 and that methylation significantly correlates with ADAM23 mRNA and protein expression. However, we were unable to detect methylation and down-regulation of the ADAM23 gene in brain tumors. Together, these results indicate that ADAM23 down-regulation by methylation in brain tumors is a rare event and it may help explain why brain tumor metastases are rarely found elsewhere in the body.

ADAM Proteins↗

PubMed2004

Epigenetic silencing of the adhesion molecule ADAM23 is highly frequent in breast tumors.

Altered cell adhesion is causally involved in tumor progression, and the identification of novel adhesion molecules altered in tumors is crucial for our understanding of tumor biology and for the development of new prognostic and therapeutic strategies. Here, we provide evidence for the epigenetic downregulation in breast tumors of the A Desintegrin And Metalloprotease domain 23 gene (ADAM 23), a member of a new family of surface molecules with roles in cell-cell adhesion and/or cell-matrix interactions. We examined the mRNA expression and methylation status of the 5' upstream region of the ADAM23 gene in different breast tumor cell lines as well as in primary breast tumors. We found ADAM23 5' hypermethylation in eight out of 12 (66.7%) tumor cell lines and in nine out of 13 (69.2%) primary tumors. Promoter hypermethylation was strongly associated with reductions in both mRNA and protein expression, with a threshold of 40-60% of modified CpG dinucleotides being required for the complete silencing of ADAM23 mRNA expression. Treatment of MCF-7 and SKBR-3 cell lines with 5'-Aza-2'-deoxycytidine led to a reactivation of ADAM23 mRNA expression and a marked decrease in the methylation level. It is worth noting that primary breast tumors with a more advanced grade showed a higher degree of methylation, suggesting that the adhesion molecule ADAM23 may be downregulated during the progression of breast cancer. Oncogene (2004) 23, 1481-1488. doi:10.1038/sj.onc.1207263 Published online 8 December 2003

ADAM Proteins↗