Prognostic significance of proliferation rate and DNA ploidy in astrocytic gliomas treated with radiotherapy

AimThe proliferative potential, and DNA ploidy in 50 brain tumours (15 grade I & II, and 35 grade III & IV astrocytomas) were investigated using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry.Materials/MethodsTumour samples taken from each patient during surgery were incubated in vitro for one hour at 37°C with bromodeoxyuridine (BrdUrd), using the high pressure oxygen method. The percentage of BrdUrd-labelled cells (BrdUrd Labelling index, BrdUrd LI), and the total DNA content were evaluated. After surgery, 21 patients received conventionally fractionated radiotherapy (RT), 11 patients received accelerated RT, and 18 patients underwent hypofractionated RT.ResultsThe tumours showed variability in BrdUrd LI values, which ranged from 0.3 to 15.8%. A significantly higher mean value for BrdUrd LI was shown in grades AIII & IV (3.5%), than in astrocytomas of grades AI & II (1.5%, p=0.005). A lower though not statistically significant percentage of DNA aneuploidy was observed in low-grade (40.2%) glioma than was seen in high-grade (65.7%) glioma. Univariate analysis showed that younger (≤50 years) patients (p=0.001), those with AI & II glioma (p=0.000), low tumour proliferation rate (BrdUrd LI ≤2.1%, p=0.006) and conventional or hypofractionated RT (p=0.000) had a significantly higher 5-year survival rate. Tumour ploidy had no influence on patients’ survival (p=0.261). However, a Cox multivariate analysis showed that only the patients’ age (>50 years), high grade tumours (AIII & IV) and accelerated RT were significantly unfavourable prognostic factors in terms of survival.ConclusionsTo improve RT results, younger patients (≤50 years) with fast proliferating tumours should receive more aggressive treatment

Gene expression profiling of blood in ruptured intracranial aneurysms : in search of biomarkers

The molecular mechanisms underlying the systemic response to subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms (RAs) are not fully understood. We investigated whether the analysis of gene expression in peripheral blood could provide clinically relevant information regarding the biologic consequences of SAH. Transcriptomics were performed using Illumina HumanHT-12v4 microarrays for 43 RA patients and 18 controls (C). Differentially expressed transcripts were analyzed for overrepresented functional groups and blood cell type-specific gene expression. The set of differentially expressed transcripts was validated using quantitative polymerase chain reaction in an independent group of subjects (15 RA patients and 14 C). There were 135 differentially expressed genes (false discovery rate ⩽1%, absolute fold change ⩾1.7): the abundant levels of 78 mRNAs increased and 57 mRNAs decreased. Among RA patients, transcripts specific to T lymphocyte subpopulations were downregulated, whereas those related to monocytes and neutrophils were upregulated. Expression profiles of a set of 16 genes and lymphocyte-to-monocyte-and-neutrophil gene expression ratios distinguished RA patients from C. These results indicate that SAH from RAs strongly influences the transcription profiles of blood cells. A specific pattern of these changes suggests suppression in lymphocyte response and enhancements in monocyte and neutrophil activities. This is probably related to the immunodepression observed in SAH

Gene Expression Profiling of Blood in Ruptured Intracranial Aneurysms: in Search of Biomarkers

The molecular mechanisms underlying the systemic response to subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms (RAs) are not fully understood. We investigated whether the analysis of gene expression in peripheral blood could provide clinically relevant information regarding the biologic consequences of SAH. Transcriptomics were performed using Illumina HumanHT-12v4 microarrays for 43 RA patients and 18 controls (C). Differentially expressed transcripts were analyzed for overrepresented functional groups and blood cell type-specific gene expression. The set of differentially expressed transcripts was validated using quantitative polymerase chain reaction in an independent group of subjects (15 RA patients and 14 C). There were 135 differentially expressed genes (false discovery rate ⩽1%, absolute fold change ⩾1.7): the abundant levels of 78 mRNAs increased and 57 mRNAs decreased. Among RA patients, transcripts specific to T lymphocyte subpopulations were downregulated, whereas those related to monocytes and neutrophils were upregulated. Expression profiles of a set of 16 genes and lymphocyte-to-monocyte-and-neutrophil gene expression ratios distinguished RA patients from C. These results indicate that SAH from RAs strongly influences the transcription profiles of blood cells. A specific pattern of these changes suggests suppression in lymphocyte response and enhancements in monocyte and neutrophil activities. This is probably related to the immunodepression observed in SAH