Search results for "LB"
showing 10 items of 5653 documents
Non-canonical NF-κB pathway activation predicts outcome in borderline oestrogen receptor positive breast carcinoma
2016
Background: NF-κB signalling appears deregulated in breast tumours. The purpose of this study was to determine whether the non-canonical NF-κB pathway, is activated in oestrogen receptor positive (ER+) breast cancer, to identify any correlation between its activity and the clinico-pathological phenotype and to explore whether NF-κB2 and RelB subunits and/or any of their target genes might be used as a predictive marker. Methods: Two independent cohorts of ER+ early breast cancer patients treated with adjuvant endocrine therapy were included in the study. Activation of RelB and NF-κB2 subunits was determined in a training set of 121 patients by measuring DNA-binding activities in nuclear ext…
Contribution of MUTYH variants to male breast cancer risk: results from a multicenter study in Italy
2018
Inherited mutations in BRCA1, and, mainly, BRCA2 genes are associated with increased risk of male breast cancer (MBC). Mutations in PALB2 and CHEK2 genes may also increase MBC risk. Overall, these genes are functionally linked to DNA repair pathways, highlighting the central role of genome maintenance in MBC genetic predisposition. MUTYH is a DNA repair gene whose biallelic germline variants cause MUTYH-associated polyposis (MAP) syndrome. Monoallelic MUTYH variants have been reported in families with both colorectal and breast cancer and there is some evidence on increased breast cancer risk in women with monoallelic variants. In this study, we aimed to investigate whether MUTYH germline v…
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…
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…
Metronomic oral vinorelbine in patients with advanced non-small cell lung cancer progressing after nivolumab immunotherapy: a retrospective analysis
2020
Purpose The availability of immune checkpoint inhibitors has deeply changed the therapeutic scenario of patients with advanced non-small cell lung cancer (NSCLC). Up until now, chemotherapy still represents the first-line treatment for patients with advanced NSCLC not harbouring genetic mutations or lacking high expression of programmed death ligand even if the addition of immunotherapy to first-line chemotherapy has recently been shown to improve clinical outcome. We carried out a multi-institutional retrospective analysis on third-line chemotherapy with metronomic oral vinorelbine (VNR) in a series of patients with metastatic NSCLC pre-treated with first-line chemotherapy and second-line …
Dose-Dense Chemotherapy in Metastatic Breast Cancer: Shortening the Time Interval for a Better Therapeutic Index
2015
Despite the advancement of targeted therapies in metastatic breast cancer, chemotherapy is still of pivotal importance. The concept of dose density is known to increase the efficacy of chemotherapy. In metastatic disease, preservation of the quality of life is equally important. Because of this, weekly regimens are a cornerstone in metastatic disease. Taxanes like paclitaxel or nab-paclitaxel as well as antracyclines are often used in palliative treatment. Further advances to increase dose density have led to the concept of daily metronomic schedules with oral chemotherapeutic drugs like cyclophosphamide, capecitabine, or vinorelbine. Metronomic chemotherapy affects tumor angiogenesis and a…
Overall survival results from the randomized phase II study of palbociclib (P) in combination with letrozole (L) vs letrozole alone for frontline tre…
2017
1001 Background: Preclinical data identified a synergistic role for P and hormone blockade in blocking growth of ER+ breast cancer (BC) cell lines. PALOMA-1 was an open-label phase II trial comparing progression-free survival (PFS) in patients (pts) with advanced ER+/HER2– BC treated with P+L or L alone. Median PFS increased with addition of P to L to 20.2 mos (vs 10.2 mos with L alone; HR = 0.488), with an acceptable safety profile, leading to accelerated approval by the US FDA. These results were confirmed in the phase 3 PALOMA-2 trial. At the time of the final PFS analysis, overall survival (OS) data were immature with only 61 events in both arms and a median follow-up of < 30 mos wi…
Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue
2018
Abstract Background Gene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Patients and methods Here, we applied the computational method CIBERSORT to generate a 1028-gene matrix incorporating signatures of 17 immune and stromal cytotypes. Then, we carried out a deconvolution on publicly available GEP data of 482 untreated DLBCLs to reveal associations between clinical outcomes and proportions of putative tumor-infiltrating cell types. Forty-five genes related to peculiar prognostic cytotypes were selected and their expression …
Therapeutic Plasmapheresis with Albumin Replacement in Alzheimer’s Disease and Chronic Progressive Multiple Sclerosis: A Review
2020
Background: Reducing the burden of beta-amyloid accumulation and toxic autoimmunity-related proteins, one of the recognized pathophysiological markers of chronic and common neurological disorders such as Alzheimer’s disease (AD) and multiple sclerosis (MS), may be a valid alternative therapy to reduce their accumulation in the brain and thus reduce the progression of these disorders. The objective of this review was to evaluate the efficacy of plasmapheresis (PP) in AD and chronic progressive MS patients (in terms of improving clinical symptoms) and to analyze its safety and protocols. Methods: Articles related to this topic and published without time limitations in the Medline, and C…
Palbociclib - from Bench to Bedside and Beyond.
2016
Endocrine therapy is the cornerstone in the treatment of hormone receptor-positive breast cancer. During the last decades, much has been learned about the subtle regulation of the cell cycle. In this tightly regulated network, cyclin-dependent kinases (CDKs) play a pivotal role. Especially CDK4/6 is the key regulator of the G1-S transition. Realizing its importance, specific inhibitors of CDK4/6 were developed. The drug most advanced in clinical development in this class is palbociclib (PD 0332991). This review highlights preclinical data and brings into focus early clinical trials that led to an accelerated approval by the US Food and Drug Administration (FDA) as first-line treatment in co…