1,721,215 research outputs found
The plodding diagnosis of monogenic autoinflammatory diseases in childhood: from the clinical scenery to laboratory investigation.
No full textAutoinflammatory diseases (AID) are inherited errors of innate immunity which, although individually uncommon, collectively set up an emerging chapter of medicine. Careful analysis and identification of AID is essential to prompt effective treatment and improve survival and quality of life in these patients. Research into pediatric AID is lagging behind studies in adults, though a better understanding of AID in infancy could lead to improved diagnostic protocols and reduce long-term disability. This review provides a detailed summary of monogenic AID in childhood to help pediatricians correctly recognize these conditions and also highlight recent developments in the laboratory diagnostic work-up
Main implications related to the switch to BRCA1/2 tumor testing in ovarian cancer patients: a proposal of a consensus
No full textSince the approval of the first poly (adenosine diphosphate [ADP]) ribose polymerase inhibitor (PARPi; olaparib [LynparzaTM]) for platinum-sensitive relapsed high grade ovarian cancer, with either germline or somatic BRCA1/2 deleterious variants, the strategies for BRCA1/2 are dynamically changing. Along with germline testing within the context of familial or sporadic ovarian cancer, patients are now being referred for BRCA1/2 genetic assay above all for treatment decisions: in this setting tumour BRCA assay can allow to identify an estimated 3-9% of patients with peculiar somatic BRCA1/2 mutations. These women could also benefit from PARPi therapy. This new type of approach is really challenging, in particular due to the technical and analytical difficulties regarding low quality DNA deriving from formalin-fixed, paraffin-embedded (FFPE) specimens.
Aim: in this manuscript, we try to a) underline many issues related to BRCA1/2 analysis by next generation sequencing technologies (NGS), b) provide some responses to many questions regarding this new paradigm related to OvCa patients' management. Some considerations for incorporating genetic analysis of ovarian tumour samples into the patient pathway and ethical requirements are also provided.
Methods: we used our retrospective data based on thousands of ovarian cancer women sequenced for BRCA1/2 genes.
Discussion: tumor BRCA1/2 assay should be rapidly introduced in routine laboratory practice as first line testing by using harmonized pipelines based on consensus guidelines
BRCA to the future: towards best testing practice in the era of personalised healthcare
No full textNo abstract Availabl
Insulin-like growth factor system and sporadic malignant melanoma.
No full textInsulin and insulin-like growth factors (IGFs) are important regulators of energy metabolism and growth. Several findings have outlined an important role played by this family of molecules in both tumor maintenance and development. Despite the established contribution of the IGF system in carcinogenesis, little and contrasting data have been reported concerning the intertwined relationships between melanoma and this family of molecules. The present minireview aims to summarize the main topics and evidence concerning this malignant skin cancer, with a focus on the following: i) melanoma and cell proliferation effects induced by the IGF system, ii) in vitro and in vivo experimental data, and iii) targeting studies. Because of consistent findings regarding the role of the IGF-1 receptor in the modulation of IGF-1 activity, possible therapeutic strategies combining the use of antisense oligonucleotides against IGF-1 receptor mRNA could be applied in the future
Respiratory care and Topics about serum levels of seven cytokines in premature newborns undergoing different ventilatory procedures
No full textMeta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers: a HuGE-GSEC review.
Full text linkThe association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a meta-analysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.edu/research/ccps/ccontrol/index.html ). Thirty publications used in the meta-analysis included a total of 7783 subjects (3177 cases and 4606 controls); 21 datasets, 9397 subjects (3130 cases and 6267 controls) were included in the pooled analysis. The GSTM1 deletion was 2-fold more likely to occur in African American and African cases than controls (odds ratio: 1.7, 95% confidence interval: 0.9-3.3), although this was not observed among whites (odds ratio: 1.0, 95% confidence interval: 0.9-1.1). The meta-analysis and pooled analysis showed a significant association between oral and pharyngeal cancer and the CYP1A1 MspI homozygous variant (meta-ORm2/m2: 1.9, 95% confidence interval: 1.4-2.7; Pooled ORm2m2: 2.0, 95% confidence interval: 1.3-3.1; ORm1m2 or [infi]m2m2: 1.3, 95% confidence interval: 1.1-1.6). The association was present for the CYP1A1 (exon 7) polymorphism (ORVal/Val: 2.2, 95% confidence interval: 1.1-4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. Our findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer
p.H282N and p.Y191H: 2 novel CYP21A2 mutations in Italian congenital adrenal hyperplasia patients
No full textMore than 90\% of all cases of congenital adrenal hyperplasia (CAH) result from steroid 21-hydroxylase gene (CYP21A2) mutations. The CYP21A2 gene is located in the human leukocyte antigen (HLA) class III region on the short arm of chromosome 6p21.3, along with an inactive pseudogene, CYP21A1P, that is 98\% homologous in its coding sequence with CYP21A2. Most CYP21A2 mutations result from intergenic recombinations between CYP21A2 and the closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for only 5\% to 10\% of 21-hydroxylase deficiency alleles. However, detection of these rare and spontaneous mutations has continued to expand worldwide. We identified 2 novel CYP21A2 missense mutations (p.H282N and p.Y191H) in 2 Italian patients with simple-virilizing and nonclassic CAH forms. Functional analysis of these CYP21A2 mutations was performed. Functional in vitro assay for mutagenized CYP21A2 enzymes was performed in transiently transfected mammalian cells to test the residual enzyme activity and the apparent kinetic values. The residual activities obtained allowed us to classify the p.H282N and p.Y191H variants as simple-virilizing and nonclassic CAH associated mutations, respectively. These results correlate with the rate of severity of the patients' disease. This finding provides a further contribution for assisting in the diagnosis of CAH patients
Circulating fetal cell-free DNA and prenatal molecular diagnostics: are we ready for consensus?
Full text linkAbstract Circulating fetal cell-free DNA (cffDNA) is emerging as the most reliable known target for prenatal molecular diagnostics. Different points of view are expressed in literature regarding the safe use of cffDNA for all types of molecular tests, above all those used to detect maternal DNA rather than fetal mutation. The aim of the present study was therefore to achieve consensus on guidelines conducive to standardizing current procedures, which differ between laboratories, and to design stringent technical protocols for the analysis of cffDNA
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