Biomedical subjects

Gilson S Baia

Publications and source records attributed to Gilson S Baia.

3 recordsLinked to original sources

PubMed2007

Expression of the hypoxia marker carbonic anhydrase 9 is associated with anaplastic phenotypes in meningiomas.

PURPOSE: Hypoxia in the tumor microenvironment triggers a variety of genetic and adaptive responses that regulate tumor growth. Tumor hypoxia is often associated with more malignant phenotypes, resistance to therapy, and poor survival. The purpose of this study was to evaluate the prevalence of hypoxia in meningiomas using the endogenous hypoxia marker carbonic anhydrase 9 (CA9) and to relate the expression of CA9 to tumor vascularity, histopathologic grade, and clinical variables, such as recurrent tumor status. EXPERIMENTAL DESIGN: Expression of CA9 and CD34, an endothelial cell marker, was examined in serial paraffin-embedded sections by immunohistochemistry in 25 grade 1, 17 grade 2, and 20 grade 3 meningiomas. Areas of immunoreactivity were semiquantitatively scored and correlated to clinical variables using Statistical Analysis System statistical software. RESULTS: Approximately 50% (29 of 62) of all meningiomas contained regions of hypoxia as judged by expression of CA9, and this expression was significantly associated with higher-grade histology (P = 0.001). In contrast, vascularity, as assessed by the percentage of vascular hotspots, was inversely associated with tumor grade (P = 0.023) and was not associated with CA9 expression. Among lower-grade meningiomas, CA9 expression tended to be more common in recurrent tumors. CONCLUSIONS: Tumor hypoxia is an endogenous feature of meningiomas, and therapeutic regimens should include strategies to target the subpopulation of hypoxic as well as the normoxic cells within the tumor. Hypoxia in meningiomas is associated with an aggressive phenotype. Further studies to define the contribution of hypoxia to meningioma pathophysiology are warranted.

Adult↗

PubMed2006

A genetic strategy to overcome the senescence of primary meningioma cell cultures.

Even though meningiomas are the second most common brain tumor in adults, little is known about the molecular basis of their growth and development. The lack of suitable cell culture model systems is an impediment to this understanding. Most studies on meningiomas rely on primary, early passage cell lines that eventually senesce or a few established cell lines that have been derived from aggressive variants of meningiomas. We have isolated three primary meningioma cell lines that are negative for telomerase activity. We can overcome the senescence of a Grade III derived meningioma cell line by expressing the telomerase catalytic subunit (hTERT), whereas Grade I meningioma cell lines require the expression of the human papillomavirus E6 and E7 oncogenes in conjunction with hTERT. Meningioma cell lines, immortalized in this manner, maintain their pre-transfection morphology and form colonies in vitro. We have confirmed the meningothelial origin of these cell lines by assessing expression of vimentin and desmoplakin, characteristic markers for meningiomas. Additionally, we have karyotyped these cell lines using array CGH and shown that they represent a spectrum of the genetic diversity seen in primary meningiomas. Thus, these cell lines represent novel cellular reagents for investigating the molecular oncogenesis of meningiomas.

Biomarkers, Tumor↗

PubMed2004

A transcript finishing initiative for closing gaps in the human transcriptome.

We report the results of a transcript finishing initiative, undertaken for the purpose of identifying and characterizing novel human transcripts, in which RT-PCR was used to bridge gaps between paired EST clusters, mapped against the genomic sequence. Each pair of EST clusters selected for experimental validation was designated a transcript finishing unit (TFU). A total of 489 TFUs were selected for validation, and an overall efficiency of 43.1% was achieved. We generated a total of 59,975 bp of transcribed sequences organized into 432 exons, contributing to the definition of the structure of 211 human transcripts. The structure of several transcripts reported here was confirmed during the course of this project, through the generation of their corresponding full-length cDNA sequences. Nevertheless, for 21% of the validated TFUs, a full-length cDNA sequence is not yet available in public databases, and the structure of 69.2% of these TFUs was not correctly predicted by computer programs. The TF strategy provides a significant contribution to the definition of the complete catalog of human genes and transcripts, because it appears to be particularly useful for identification of low abundance transcripts expressed in a restricted set of tissues as well as for the delineation of gene boundaries and alternatively spliced isoforms.

Alternative Splicing↗