Introduction
Lung cancer is formerly the highest cause of mortality among tumor pathologies worldwide. There are no validated techniques for an early detection of pulmonary cancer lesions other than low-dose helical CT-scan. Unfortunately, this method have some downside effects.
Recent studies have laid the basis for development of exosomes-based techniques to screen/diagnose lung cancers. As the isolation of circulating exosomes is a minimally invasive procedure, this technique opens new possibilities for diagnostic applications.
Methods
We used a first set of 30 plasma samples from as many patients, including 10 patients affected by Lung Adenocarcinomas, 10 with Lung Granulomas and 10 healthy smokers matched for age and sex as negative controls. Wide range microRNAs analysis (742 microRNAs) was performed by quantitative RT-PCR. Data were compared by lesion characteristics using WEKA software for statistics and modeling. Subsequently, selected microRNAs were evaluated on an independent larger group of samples (105 specimens: 50 Lung Adenocarcinomas, 30 Lung Granulomas and 25 healthy smokers).
Results
This analysis led to the selection of 4 microRNAs to perform a screening test (miR-378a, miR-379, miR-139-5p and miR-200b-5p), useful to divide population into 2 groups: nodule (lung adenocarcinomas+carcinomas) and non-nodule (healthy former smokers). Six microRNAs (miR-151a-5p, miR-30a-3p, miR-200b-5p, miR-629, miR-100 and miR-154-3p) were selected for a second test on the “nodule” population to discriminate between lung adenocarcinoma and granuloma.
Conclusions
“Screening test” has shown 97.5% sensitivity, 72.0% specificity, AUC ROC of 90.8%. “Diagnostic test” had 96.0% sensitivity, 60.0% specificity, AUC ROC of 76.0%.
Further evaluation is needed to confirm the predictive power of those models on higher cohorts of samples.
In this study, high ARV of daytime systolic BP resulted in an independent predictor of cardiovascular risk in hypertensive patients, while high s.d. did not. Our data suggest that, in comparison to s.d., ARV could be a more appropriate index of BP variability and a more useful predictor of outcomes.
Key Points• Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation.• Haploidentical hematopoietic stem cell transplantation for hematologic malignancies.Eighty patients with high-risk hematologic malignancies underwent unmanipulated, G-CSF-primed BM transplantation from an haploidentical family donor. Patients were transplanted in first or second complete remission (CR, standard-risk: n ؍ 45) or in > second CR or active disease (high-risk: n ؍ 35). The same regimen for GVHD prophylaxis was used in all cases. The cumulative incidence (CI) of neutrophil engraftment was 93% ؎ 0.1%. The 100-day CIs for II-IV and III-IV grade of acute GVHD were 24% ؎ 0.2% and 5% ؎ 0.6%, respectively. The 2-year CI of extensive chronic GVHD was 6% ؎ 0.1%. The 1-year CI of treatment-related mortality was 36% ؎ 0.3%. After a median follow-up of 18 months, 36 of 80 (45%) patients are alive in CR. The 3-year probability of overall and disease-free survival for standard-risk and high-risk patients was 54% ؎ 8% and 33% ؎ 9% and 44% ؎ 8% and 30% ؎ 9%, respectively. In multivariate analysis, disease-free survival was significantly better for patients who had standard-risk disease and received transplantations after 2007. We conclude that unmanipulated, G-CSF-primed BM transplantation from haploidentical family donor provides very encouraging results in terms of engraftment rate, incidence of GVHD and survival and represents a feasible, valid alternative for patients with high-risk malignant hematologic diseases, lacking an HLA identical sibling and in need to be urgently transplanted. (Blood. 2013;121(5): 849-857)
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