Genetic architecture of ALS in Sardinia.

Conserved populations, such as Sardinians, displaying elevated rates of familial or sporadic amyotrophic lateral sclerosis (ALS) provide unique information on the genetics of the disease. Our aim was to describe the genetic profile of a consecutive series of ALS patients of Sardinian ancestry. All ALS patients of Sardinian ancestry, identified between 2008 and 2013 through the Italian ALS Genetic Consortium, were eligible to be included in the study.

MicroRNA-425-3p predicts response to sorafenib therapy in patients with hepatocellular carcinoma.

Background & Aims: Sorafenib is the standard of care in advanced hepatocellular carcinoma (HCC), however no criteria have been established to select patients likely to benefit from this therapy. In this study, we evaluated the predictive role of microRNAs (miRNAs) in this setting of patients.

Methods: We profiled 522 miRNA in a series of 26 HCC patients treated with sorafenib (training set) and validated the results in an independent series of 58 patients (validation set).

Antitumor activity of sorafenib and imatinib in a patient with thymic carcinoma harboring c-KIT exon 13 missense mutation K642E.

We report the case of a man with an advanced nonkeratinizing squamous cell thymic carcinoma harboring c-KIT exon 13 missense mutation K642E. This aberration is rare and has never been described previously in patients with thymic cancers. It has been found in a small number of cases of gastrointestinal stromal tumor and also in several cases of acral and mucosal melanomas.

A founder MLH1 mutation in Lynch syndrome families from Piedmont, Italy, is associated with an increased risk of pancreatic tumours and diverse immunohistochemical patterns.

The MLH1 c.2252_2253delAA mutation was found in 11 unrelated families from a restricted area south-west of Turin among 140 families with mutations in the mismatch repair genes. The mutation is located in the highly conserved C-terminal region, responsible for dimerization with the PMS2 protein.

Atypical primary pulmonary meningioma: a report of a case suspected of being a lung metastasis.

Primary extracranial and extraspinal meningiomas are very rare tumours, and primary pulmonary ones are even more uncommon. They present as a solitary pulmonary nodule, and most of them are benign, except for three cases. We describe a primitive atypical pulmonary meningioma first suspected of being a metastasis in a patient during follow-up ten years after therapy for breast cancer.

Prevalence and clinicopathologic correlates of O⁶-methylguanine-DNA methyltransferase methylation status in patients with triple-negative breast cancer treated preoperatively by alkylating drugs.

Background: Predictive factors of benefit from specific chemotherapy regimens are not currently available in triple-negative breast cancer (TNBC). MGMT (O(6)-methylguanine-DNA methyltransferase) controls DNA repair pathways, and its epigenetic silencing is used for predicting the response to the alkylating drug temozolomide in patients with glioma.

Materials And Methods: The study population was composed of 84 patients with TNBC treated with alkylating agents and evaluated for clinicopathologic parameters (tumor shrinkage and pathologic complete response [pCR]).

Phase ib of sorafenib in combination with everolimus in patients with advanced solid tumors, selected on the basis of molecular targets.

Background: Molecular alterations of the PI3K and Ras pathways often occur in human cancer. In this trial, the pharmacokinetics, toxicity, and activity of two drugs inhibiting these pathways-everolimus and sorafenib-were investigated.

Methods: Thirteen patients with progressing solid tumors were treated with everolimus and sorafenib, according to a 3+3 scheme.

Factors affecting distribution and abundance of Aspergillus section Nigri in vineyard soils from grapevine growing regions of Argentina.

Background: Aspergillus species belonging to section Nigri are the main fungi responsible for ochratoxin (OTA) contamination in grapes and wine. These species live as saprophytes in the superficial layer of the vineyard soil. We evaluated the biodiversity of potentially ochratoxigenic strains of Aspergillus section Nigri isolated from vineyard soils from different grapevine growing regions of Argentina.

Gene expression profiling reveals GC and CEACAM1 as new tools in the diagnosis of lung carcinoids.

Background: Classification of lung carcinoids into typical and atypical is a diagnostic challenge since no immunohistochemical tools are available to support pathologists in distinguishing between the two subtypes. A differential diagnosis is essential for clinicians to correctly discuss therapy, prognosis and follow-up with patients. Indeed, the distinction between the two typical and atypical subtypes on biopsies/cytological specimens is still unfeasible and sometimes limited also after radical surgeries.

De novo nonsense mutation of the FUS gene in an apparently familial amyotrophic lateral sclerosis case.

Mutations in C9ORF72, SOD1, TARDBP, and FUS genes account for approximately two-third of familial cases and 5% of sporadic amyotrophic lateral sclerosis (ALS) cases. We present the first case of an ALS patient carrying a de novo nonsense mutation in exon 14 of the FUS gene (c.1483c>t; p.

Stem cell transplantation effectively occludes bronchopleural fistula in an animal model.

Background: Bronchopleural fistula after lung resection still represents a challenging life-threatening complication for thoracic surgeons. Considering its extremely high mortality rate, an effective treatment is urgently required. Our project investigated the hypothesis of experimental bronchopleural fistula closure by bronchoscopic injection of autologous bone marrow-derived mesenchymal stem cells into the cavity of the fistula, evaluating its feasibility and safety in a large animal model.

A case of NUT midline carcinoma with no HPV infection, slight EWSR1 rearrangement and strong expression of EGFR.

NUT midline carcinoma (NMC) is a rare neoplasm with a poor prognosis and involving mostly young patients. Here we describe a classic NMC with a BRD4-NUT fusion gene in a middle-aged woman. We also analyzed some biological features that could potentially influence its clinical behavior such as HPV infection, EWSR1 rearrangement, and the status of the EGFR gene.

A rare case of lung metastasis from a malignant adenomyoepithelioma of the breast: histological features and therapeutic implications.

We present a rare case of lung metastasis from a malignant adenomyoepithelioma of the breast. A 44-year-old woman was surgically treated in 2008 for a malignant adenomyoepithelioma of the breast. Shortly after, two lung nodules were detected through a CT scan, and a diagnosis of malignant adenomyoepithelioma was rendered.

Identification of an 18 bp deletion in the TWIST1 gene by CO-amplification at lower denaturation temperature-PCR (COLD-PCR) for non-invasive prenatal diagnosis of craniosynostosis: first case report.

Background: Non-invasive prenatal diagnosis has found application in a limited number of genetic diseases due to the difficulty in detecting a few copies of fetal mutated sequences in the presence of a large excess of wild-type maternal alleles, even in the case of single-base mutations.

Methods: We developed conditions for the enrichment of fetal mutated alleles in maternal plasma based on CO-amplification at lower denaturation temperature-PCR (COLD-PCR). In particular, we applied a full COLD-PCR protocol to the identification of a p.

Targeting ALK in patients with advanced non small cell lung cancer: biology, diagnostic and therapeutic options.

The discovery of EML4-ALK fusion gene in a subgroup of patients with lung adenocarcinoma led to the development of a new class of agents, the ALK inhibitors, and dramatically improved the clinical outcome of these patients. The striking results from clinical trials with crizotinib, the first ALK inhibitor evaluated, allowed the accelerated approval of crizotinib from the USA Food and Drug Administration (FDA). Despite the high initial results, patients acquire resistance to crizotinib, and different next generation ALK kinase inhibitors have been developed.

Lymphoscintigraphy in clinical routine practice: reproducibility and accuracy in melanoma patients with a long-term follow-up.

Introduction: The sentinel node status is the most important single factor determining overall survival for patients with localized melanoma. Preoperative lymphoscintigraphy (LS) is essential in locating the correct sentinel lymph node (SN) and the reproducibility of the method determines the accuracy of the sentinel node biopsy (SNB). This study aims at determining the reproducibility and accuracy of LS in routine clinical practice after long-term follow-up.

Validation of a proliferation-based expression signature as prognostic marker in early stage lung adenocarcinoma.

Purpose: New prognostic markers to guide treatment decisions in early stage non-small cell lung cancer are necessary to improve patient outcomes. In this report, we assess the utility of a predefined mRNA expression signature of cell-cycle progression genes (CCP score) to define 5-year risk of lung cancer-related death in patients with early stage lung adenocarcinoma.

Experimental Design: A CCP score was calculated from the mRNA expression levels of 31 proliferation genes in stage I and stage II tumor samples from two public microarray datasets [Director's Consortium (DC) and GSE31210].

Tissue genotyping of 37 in situ and invasive cervical cancer with a concomitant negative HC2 HPV DNA test.

Objective: The rare occurrence of histology-proven cervical intraepithelial neoplasia grade 3 (CIN 3) or invasive cancer with a negative HC2 result is known. Tissue blocks of 37 cases of histology-diagnosed CIN 3+ with a concomitant negative HC2 test were genotyped to investigate the human papillomavirus (HPV) status within the lesion.

Methods: We considered 1,976 cervical excision specimens performed with concomitant HC2 test.

Fkh1 and Fkh2 associate with Sir2 to control CLB2 transcription under normal and oxidative stress conditions.

The Forkhead (Fkh) box family of transcription factors is evolutionary conserved from yeast to higher eukaryotes and its members are involved in many physiological processes including metabolism, DNA repair, cell cycle, stress resistance, apoptosis, and aging. In budding yeast, four Fkh transcription factors were identified, namely Fkh1, Fkh2, Fhl1, and Hcm1, which are implicated in chromatin silencing, cell cycle regulation, and stress response. These factors impinge transcriptional regulation during cell cycle progression, and histone deacetylases (HDACs) play an essential role in this process, e.

A variable fork rate affects timing of origin firing and S phase dynamics in Saccharomyces cerevisiae.

Activation (in the following referred to as firing) of replication origins is a continuous and irreversible process regulated by availability of DNA replication molecules and cyclin-dependent kinase activities, which are often altered in human cancers. The temporal, progressive origin firing throughout S phase appears as a characteristic replication profile, and computational models have been developed to describe this process. Although evidence from yeast to human indicates that a range of replication fork rates is observed experimentally in order to complete a timely S phase, those models incorporate velocities that are uniform across the genome.

EGFR tyrosine kinase inhibitors beyond focal progression obtain a prolonged disease control in patients with advanced adenocarcinoma of the lung.

Introduction: Recent data show that EGFR pathway and its inhibition maintain their role after progression of disease during EGFR TKI therapy in NSCLCs. We conducted a retrospective study with the aim of evaluating efficacy and feasibility of prosecution of EGFR TKI therapy beyond focal progression associated to locoregional radiotherapy.

Methods: We retrospectively analyzed the data of all NSCLC patients treated with EGFR TKIs in our institution from 2004 to 2012.

Positive compared with negative margins in a single-centre retrospective study on 3957 consecutive excisions of basal cell carcinomas. Associated risk factors and preferred surgical management.

The rate of margins involvement and the associated recurrence risk in basal cell carcinomas (BCCs) varies widely in published works (7%-25% and 26%-67%, respectively). This study investigated the risk factors associated with incomplete excision and their relevance in surgical management when positive margins occur in 3957 BCCs excised in 2358 patients. This study performed a multivariate analysis on the database collected from all patients operated for BCCs in the Plastic Surgery Department between 1 January 1992 and 1 September 2007.