Search results for "A2"
showing 10 items of 1101 documents
Hereditary prostate cancer – Primetime for genetic testing?
2019
Prostate cancer (PCa) remains the most common cancer in men. The proportion of all PCa attributable to high-risk hereditary factors has been estimated to 5-15%. Recent landmark discoveries in PCa genetics led to the identification of germline mutations/alterations (eg. BRCA1, BRCA2, ATM or HOXB13), single nucleotide polymorphisms or copy number variations associated with PCa incidence and progression. However, offering germline testing to men with an assumed hereditary component is currently controversial. In the present review article, we provide an overview about the epidemiology and the genetic basis of PCa predisposition and critically discuss the significance and consequence in the cli…
CAMKIIγ suppresses an efferocytosis pathway in macrophages and promotes atherosclerotic plaque necrosis
2017
Atherosclerosis is the underlying etiology of cardiovascular disease, the leading cause of death worldwide. Atherosclerosis is a heterogeneous disease in which only a small fraction of lesions lead to heart attack, stroke, or sudden cardiac death. A distinct type of plaque containing large necrotic cores with thin fibrous caps often precipitates these acute events. Here, we show that Ca2+/calmodulin-dependent protein kinase gamma (CaMKII gamma) in macrophages plays a major role in the development of necrotic, thin-capped plaques. Macrophages in necrotic and symptomatic atherosclerotic plaques in humans as well as advanced atherosclerotic lesions in mice demonstrated activation of CaMKII. We…
Functional display of an alpha2 integrin-specific motif (RKK) on the surface of baculovirus particles.
2005
The use of baculovirus vectors shows promise as a tool for gene delivery into mammalian cells. These insect viruses have been shown to transduce a variety of mammalian cell lines, and gene transfer has also been demonstrated in vivo. In this study, we generated two recombinant baculovirus vectors displaying an integrin-specific motif, RKK, as a part of two different loops of the green fluorescent protein (GFP) fused with the major envelope protein gp64 of Autographa californica M nucleopolyhedrovirus. By enzyme linked immunosorbent assays, these viruses were shown to bind a peptide representing the receptor binding site of an α2 integrin, the α2I-domain. However, the interaction was not st…
Auxiliary α2δ1 and α2δ3 Subunits of Calcium Channels Drive Excitatory and Inhibitory Neuronal Network Development
2020
VGCCs are multisubunit complexes that play a crucial role in neuronal signaling. Auxiliary α2δ subunits of VGCCs modulate trafficking and biophysical properties of the pore-forming α1 subunit and trigger excitatory synaptogenesis. Alterations in the expression level of α2δ subunits were implicated in several syndromes and diseases, including chronic neuropathic pain, autism, and epilepsy. However, the contribution of distinct α2δ subunits to excitatory/inhibitory imbalance and aberrant network connectivity characteristic for these pathologic conditions remains unclear. Here, we show that α2δ1 overexpression enhances spontaneous neuronal network activity in developing and mature cultures of …
Recommendations for the implementation of BRCA testing in the care and treatment pathways of ovarian cancer patients
2016
In the last 20 years, following the identification of the BRCA1 and BRCA2 genes (hereinafter referred to as the BRCA genes), preventive pathways have been developed for the identification and clinical management of individuals at high risk of developing breast and ovarian cancer due to the presence of a pathogenic variant in either of these genes. These pathways are aimed at educating high-risk subjects on programs targeted toward early diagnosis and cancer risk reduction. The approval of a novel class of drugs, the PARP enzyme inhibitors, for the treatment of ovarian cancer patients carrying high-risk BRCA pathogenic variants has changed this scenario. BRCA testing, in addition to providin…
Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants i…
2020
Simple Summary Many bilateral breast cancer patients with increased hereditary susceptibility to breast cancer result negative for BRCA1 or BRCA2 pathogenic variants and, thus, need a further genetic testing through a broader gene panel. Some patients with negative test result for BRCA1/2 pathogenic variants may harbor pathogenic variants in other breast cancer susceptibility genes, including ATM, CHEK2, PALB2, PTEN, TP53. Of course, the use of a multi-gene panel provides clinicians more information through a single test. Therefore, we focused on potential clinical impact of a NGS-based multi-gene panel testing in bilateral breast cancer patients, in order to evaluate the utility of perform…
Prevalence and Spectrum of Germline BRCA1 and BRCA2 Variants of Uncertain Significance in Breast/Ovarian Cancer: Mysterious Signals From the Genome
2021
About 10–20% of breast/ovarian (BC/OC) cancer patients undergoing germline BRCA1/2 genetic testing have been shown to harbor Variants of Uncertain Significance (VUSs). Since little is known about the prevalence of germline BRCA1/2 VUS in Southern Italy, our study aimed at describing the spectrum of these variants detected in BC/OC patients in order to improve the identification of potentially high-risk BRCA variants helpful in patient clinical management. Eight hundred and seventy-four BC or OC patients, enrolled from October 2016 to December 2020 at the “Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of University Hospital Policlini…
Recurrent Mutations in BRCA1, BRCA2, RAD51C, PALB2 and CHEK2 in Polish Patients with Ovarian Cancer
2021
The aim of the study was to analyze the frequency and magnitude of association of 21 recurrent founder germline mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 genes with ovarian cancer risk among unselected patients in Poland. We genotyped 21 recurrent germline mutations in BRCA1 (9 mutations), BRCA2 (4 mutations), RAD51C (3 mutations), PALB2 (2 mutations), and CHEK2 (3 mutations) among 2270 Polish ovarian cancer patients and 1743 healthy controls, and assessed the odds ratios (OR) for developing ovarian cancer for each gene. Mutations were detected in 369 out of 2095 (17.6%) unselected ovarian cancer cases and 117 out of 1743 (6.7%) unaffected controls. The ovarian cancer risk was ass…
Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives
2019
The current availability of new Poly(ADP-ribose) Polymerase (PARP)-inhibitors for the treatment of ovarian cancer patients independently of the presence of a BRCA pathogenic variant, together with the validation of somatic test for the analysis of BRCA1/2 genes, involves the need to optimise the guidelines for BRCA testing. The AIOM-SIGU-SIBIOC-SIAPEC-IAP Italian Scientific Societies, in this position paper, recommend the implementation of BRCA testing with 2 main objectives: the first is the identification of ovarian cancer patients with higher probability of benefit from specific anticancer treatments (test for response to therapy); the second goal, through BRCA testing in the family memb…
Prevalence and Clinicopathological Characteristics of Moderate and High-Penetrance Genes in Non-BRCA1/2 Breast Cancer High-Risk Spanish Families
2021
(1) Background: Over the last decade, genetic counseling clinics have moved from single-gene sequencing to multigene panel sequencing. Multiple genes related to a moderate risk of breast cancer (BC) have emerged, although many questions remain regarding the risks and clinical features associated with these genes. (2) Methods: Ninety-six BC index cases (ICs) with high-risk features for hereditary breast and ovarian cancer (HBOC) and with a previous uninformative result for BRCA1/2 were tested with a panel of 41 genes associated with BC risk. The frequency of pathogenic variants (PVs) was related to the clinical characteristics of BC. (3) Results: We detected a PV rate of 13.5% (excluding two…