Biomedical subjects

Carolina Belli

Publications and source records attributed to Carolina Belli.

5 recordsLinked to original sources

PubMed2005

Tumor transition zone: a putative new morphological and functional hallmark of tumor aggressiveness.

A small primary or secondary tumor load can occasionally induce more deleterious effects than a histologically identical larger one. In the four murine models studied herein this enhanced tumor aggressiveness could not be attributed to NRAS mutations or other hereditary changes, differential vascularization of live tumor tissues, or necrosis content. Instead, the main tumor feature associated with a more aggressive behavior was the presence of a high number of vessels, sometimes filled with inflammatory cells, inside a tumor area, which we have identified and designated as the transition zone between the live and the necrotic zones. Our experiments suggest that during tumor growth, different cachectic factors are produced within the transition and necrotic zones by dying tumor cells and by tumor infiltrating macrophages only reaching the general circulation through the vessels present in the transition zone. Therefore, a small tumor displaying high vascularization of its transition area could be harmful to its host, while, in contrast, a large tumor could behave as a relatively benign one if its transition zone exhibited little or no vascularization, and in consequence its cachectic factors remained "trapped." Similar histological images to those observed in mice were seen in a significant percentage of human cancer biopsies, raising the possibility that such images might have a prognostic value.

Animals↗

PubMed2004

A single, multiplex analysis for all relevant activating NRAS gene mutations using heteroduplex generators.

We describe a multiplex polymerase chain reaction (PCR)-based test that detected all relevant NRAS activating mutations using a single PCR followed directly by electrophoresis. The test uses a Universal Heteroduplex Generator (UHG) to detect exon-2 (codon 61) NRAS mutations in multiplex with an UHG for exon-1 (codons 12 and 13). The method differentiated all 19 relevant mutations in these exons and showed a mutation independent sensitivity of approximately 6%. The sensitive, specific detection of all NRAS activating mutations using this single rapid test represents a minimum workload and could be applied readily for large-scale screening and for routine analysis.

Base Sequence↗

PubMed2003

Rapid detection of exon 1 NRAS gene mutations using universal heteroduplex generator technology.

Specific NRAS oncogene missense mutations have been frequently found in some tumors and several hematological diseases, especially in those of myeloid origin. There is a wide range of PCR-based methods for screening and detection of NRAS exon 1 single-base substitutions. However, there are disadvantages and ambiguities associated with these techniques because all of them require either separate probes, separate PCR amplifications, or complicated post-PCR manipulations. This report describes a new approach for detection of NRAS gene mutations at codon 12 and 13 based on the DNA heteroduplex analysis method. The strategy relies upon differential electrophoretic behavior of induced heteroduplex molecules formed by cross-hybridization of two PCR-amplified species, the sample under analysis and the synthetic universal heteroduplex generator (UHG). The screening of a panel of all codon 12 and 13 NRAS mutant DNA variants indicated that this approach discriminates all 12 relevant mutations. The sensitivity of the method was estimated by a competitive assay where mutant alleles could be detected at a dilution level of 1 to 16 wild-type alleles. This UHG technology was tested on some clinical samples previously studied by PCR-ASO. This methodology is highly specific, sensitive, and achieves an appreciable reduction in workload and time because it requires one PCR amplification followed by polyacrylamide gel electrophoresis in standard conditions. We propose that this new approach may be applied as an alternative strategy for codon 12-13 NRAS mutations and it could be easily incorporated into the range of routine assays performed in oncology laboratories.

Codon↗

PubMed2002

Evaluation of constitutional chromosome aberrations in hematologic disorders.

We have reviewed 4164 patients with various hematologic disorders cytogenetically studied in our laboratory during the last 25 years to analyze the frequency of constitutional chromosome aberrations (CCA) and to evaluate their association with hematologic malignancies. Our population of patients included 1133 pediatric patients and 3031 adults. Twenty-four (0.58%) cases showed CCA. They included four patients with Robertsonian translocations, one patient with a balanced translocation, two patients with sex chromosome abnormalities, and 17 cases with Down syndrome (DS). Nonsignificant differences among the frequency of patients with CCA from our hematologic series and those observed in the two largest combined surveys of livebirth published (0.65-0.84%) were found. The incidence of DS patients in our population (0.41%) was approximately three times higher than of that observed at birth (0.12-0.17%; P<0.001). The total incidence of constitutional chromosome abnormalities in the non-DS hematologic patients was 0.168% (7 of 4164) lower than of that observed in the newborn population (0.51-0.67%; P<0.001). Nonsignificant differences were found when the incidences of structural aberrations and sex chromosome anomalies were individually compared with the data of the overall population. Our results suggest that the presence of a CCA, other than DS, would not predispose patients to hematologic malignancies.

Adolescent↗

PubMed2002

Detection of risk groups in myelodysplastic syndromes. A multicenter study.

BACKGROUND AND OBJECTIVES: Myelodysplastic syndromes (MDS) comprise a group of heterogeneous hematologic disorders with risk of leukemic evolution (LE). The French-American-British (FAB) co-operative group classifies them into five morphologic entities and the International Prognostic Scoring System (IPSS) proposes four groups of risk on the basis of clinical and cytogenetic variables. The aim of this study was to evaluate the application of the IPSS in our Argentine population, to test the prognostic value of its variables and to determine whether this score helps to associate prognostic subgroups of risk into FAB subtypes. DESIGN AND METHODS: Two hundred and thirty-four patients with primary MDS and a median follow-up of 28 months were evaluated using univariate analyses to determine median survival (SV) and the time to LE. The variables analyzed were FAB classification, IPSS, percentage of myeloblasts, cytogenetic groups of risk and number of cytopenias. RESULTS: Univariate analyses showed that all variables analyzed were predictive for SV and for LE in our MDS population. Application of the IPSS allowed discrimination into the 4 groups of risk and helped to identify prognostic subclasses among the FAB classification, associating 5%, 15% and 19% of cases with worse prognosis within the FAB classification of refractory anemia (RA), RA with ringed sideroblasts and RA with excess of blasts (RAEB), respectively. The IPSS was not informative for RAEB in transformation cases and would not be applied to patients with chronic myelomonocytic leukemia. INTERPRETATION AND CONCLUSIONS: This score could be applied to our MDS population, showing no geographic differences. Stratification of FAB patients according to IPSS would be helpful to develop risk-adapted therapeutic strategies.

Adolescent↗