DDB2 expression lights the way for precision radiotherapy response in PDAC cells, with or without olaparib.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Therapeutic options for PDAC are primarily restricted to surgery in the early stages of the disease or chemotherapy in advanced disease. Only a subset of patients with germline defects in BRCA1/2 genes can potentially benefit from personalized therapy, with the PARP inhibitor olaparib serving as a maintenance treatment for metastatic disease.

CRISPR/Cas9-mediated knock-in of BRCA1/2 mutations restores response to olaparib in pancreatic cancer cell lines.

Pancreatic cancer is one of the most aggressive diseases with a very poor outcome. Olaparib, a PARP inhibitor, as maintenance therapy showed benefits in patients with metastatic pancreatic adenocarcinoma bearing germline BRCA1/2 mutations. However, germline BRCA mutation has been described in only 4-7% of patients with pancreatic adenocarcinoma.

Validation of the Idylla GeneFusion assay to detect fusions and MET exon-skipping in non-small cell lung cancers.

Gene fusions and MET exon skipping drive oncogenesis in 8-9% and 3% of non-small cell lung cancers (NSCLC) respectively. Their detection are essential for the management of patients since they confer sensitivity to specific targeted therapies with significant clinical benefit over conventional chemotherapy. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) account for historical reference techniques however molecular-based technologies (RNA-based sequencing and RT-PCR) are emerging as alternative or complementary methods.

DDB2 represses epithelial-to-mesenchymal transition and sensitizes pancreatic ductal adenocarcinoma cells to chemotherapy.

Introduction: Damage specific DNA binding protein 2 (DDB2) is an UV-indiced DNA damage recognition factor and regulator of cancer development and progression. DDB2 has dual roles in several cancers, either as an oncogene or as a tumor suppressor gene, depending on cancer localization. Here, we investigated the unresolved role of DDB2 in pancreatic ductal adenocarcinoma (PDAC).

A NGS-based Blood Test For the Diagnosis of Invasive HPV-associated Carcinomas with Extensive Viral Genomic Characterization.

Purpose: Use of circulating tumor DNA (ctDNA) for diagnosis is limited regarding the low number of target molecules in early-stage tumors. Human papillomavirus (HPV)-associated carcinomas represent a privileged model using circulating viral DNA (ctHPV DNA) as a tumor marker. However, the plurality of HPV genotypes represents a challenge.

Evaluation of the Idylla ctEGFR mutation assay to detect EGFR mutations in plasma from patients with non-small cell lung cancers.

The assessment of EGFR mutations is recommended for the management of patients with non-small cell lung cancer (NSCLC). Presence of EGFR mutation is associated with response or resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI). Liquid biopsy is nowadays widely used for the detection of resistance to EGFR-TKI.

Evaluation of 3 molecular-based assays for microsatellite instability detection in formalin-fixed tissues of patients with endometrial and colorectal cancers.

Microsatellite instability (MSI) status is routinely assessed in patients with colorectal and endometrial cancers as it contributes to Lynch syndrome initial screening, tumour prognosis and selecting patients for immunotherapy. Currently, standard reference methods recommended for MSI/dMMR (deficient MisMatch Repair) testing consist of immunohistochemistry and pentaplex PCR-based assays, however, novel molecular-based techniques are emerging. Here, we aimed to evaluate the performance of a custom capture-based NGS method and the Bio-Rad ddPCR and Idylla approaches for the determination of MSI status for theranostic purposes in 30 formalin-fixed paraffin embedded (FFPE) tissue samples from patients with endometrial (n = 15) and colorectal (n = 15) cancers.

Evaluation of KRAS, NRAS and BRAF mutations detection in plasma using an automated system for patients with metastatic colorectal cancer.

Background: Cell-free DNA detection is becoming a surrogate assay for tumor genotyping. Biological fluids often content a very low amount of cell-free tumor DNA and assays able to detect very low allele frequency mutant with a few quantities of DNA are required. We evaluated the ability of the fully-automated molecular diagnostics platform Idylla for the detection of KRAS, NRAS and BRAF hotspot mutations in plasma from patients with metastatic colorectal cancer (mCRC).

Identification of Specific Tumor Markers in Vulvar Carcinoma Through Extensive Human Papillomavirus DNA Characterization Using Next Generation Sequencing Method.

Objectives: A subset of vulvar carcinomas (VC) are associated with human papillomavirus (HPV) DNA. This trait can be used to identify tumor markers for patient's follow-up. A large diversity of HPV prevalence in VC has been reported, but no data are available concerning the insertional HPV status in this tumor type.

Evaluation of KRAS, NRAS and BRAF hotspot mutations detection for patients with metastatic colorectal cancer using direct DNA pipetting in a fully-automated platform and Next-Generation Sequencing for laboratory workflow optimisation.

Background: Assessment of KRAS, NRAS (RAS) and BRAF mutations is a standard in the management of patients with metastatic colorectal cancer (mCRC). Mutations could be assessed using next-generation sequencing (NGS) or real-time PCR-based assays. Times to results are 1 to 2 weeks for NGS and 1 to 3 days for real-time PCR-based assays.

Uncommon mutational profiles of metastatic colorectal cancer detected during routine genotyping using next generation sequencing.

RAS genotyping is mandatory to predict anti-EGFR monoclonal antibodies (mAbs) therapy resistance and BRAF genotyping is a relevant prognosis marker in patients with metastatic colorectal cancer. Although the role of hotspot mutations is well defined, the impact of uncommon mutations is still unknown. In this study, we aimed to discuss the potential utility of detecting uncommon RAS and BRAF mutation profiles with next-generation sequencing.

Integrated routine workflow using next-generation sequencing and a fully-automated platform for the detection of KRAS, NRAS and BRAF mutations in formalin-fixed paraffin embedded samples with poor DNA quality in patients with colorectal carcinoma.

Background: KRAS and NRAS mutations are identified resistance mutations to anti-epidermal growth factor receptor monoclonal antibodies in patients with metastatic colorectal cancer. BRAF status is also routinely assessed for its poor prognosis value. In our institute, next-generation sequencing (NGS) is routinely used for gene-panel mutations detection including KRAS, NRAS and BRAF, but DNA quality is sometimes not sufficient for sequencing.

Usefulness of a quantitative analysis of the recovery phase patterns of the ST-segment depression in the diagnosis of coronary artery disease.

Purpose: To assess the diagnostic value of the recovery phase patterns of the ST-segment depression in patients referred for chest pain.

Patients And Methods: Continuous plots of ST-segment depression against heart rate during exercise and recovery were constructed within a population of 160 consecutive symptomatic patients who all had undergone catheterization (80 with > or = 1 stenosis > or = 50%). We used a new quantitative method of measurement allowing all kinds of rate recovery loops (even the so-called "intermediate" loops) to be considered for analysis.

[Short term blood pressure variability and baroreflex sensitivity in mild and moderate hypertensive patients "dipper and non dipper"].

Aim Of The Study: To compare heart rate (HR) and blood pressure (BP) variability in hypertensive patients with or without a fall in BP during the night.

Methods: 33 mild to moderato hypertensive patients, mean age 45 +/- 15 years, underwent an echocardiogram, a 24-hr ambultory BP monitoring (ABPM), and a 24-hr ECG monitoring. In addition, a continuous BP recording over 15 minutes was performed between 9 and 11 a.

[Heart rate and blood pressure variabilities in mild to moderate hypertensive patients with or without left ventricular hypertrophy].

Aim Of The Study: To compare heart rate (HR) and blood pressure (BP) variability in hypertensives with or without left ventricular hypertrophy (LVH).

Methods: Thirty-three mild to moderate hypertensive patients, mean age 45 +/- 15 years, underwent an echocardiogram, a 24 hr ambulatory BP monitoring (ABPM), a 24 hr ECG monitoring and a continuous BP recording over 15 minutes both in supine and standing positions, by using digital plethysmography (Finapres device).

Statistical Analysis: non parametric tests.

[Reproducibility of the blood pressure variability parameters by plethysmographic method (FINAPRES) in normotensive subject].

Aim Of The Study: to assess the reproducibility of blood pressure and heart rate variability measurements in time and frequency domain, by using a Finapres device in healthy volunteers.

Methods: 16 normotensive subjects aged 22 to 51 years underwent within a 5-day interval two non-invasive blood pressure recordings by a Finapres device over 15 minutes both in supine and standing positions, at the same time of the day.

Statistical Analysis: non parametric tests, relative errors, and intraclass correlation coefficient.

Drug-induced changes in ambulatory blood pressure and pulse pressure in patients with or without sustained hypertension.

We retrospectively studied 216 mild to moderate hypertensive patients receiving either an angiotensin converting enzyme inhibitor (ACEI) or a calcium antagonist (CA), as a once-a-day monotherapy; their blood pressure had been measured using both a sphygmomanometer and an ambulatory blood pressure recorder. Numerous discrepancies were found between the two methods of blood pressure measurement with respect to systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as pulse pressure (PP). Clinic blood pressure measurement did not show any significant differences between the effects of ACEI and those of CA, whereas ambulatory blood pressure measurements (ABPM) showed that in patients with normal ambulatory blood pressure (so-called 'white coat' hypertensive patients), ACEI only (but not CA) significantly lowered SBP, DBP and PP.

Comparison of the diagnostic accuracy of different methods of measurement of heart rate-adjusted ST-segment depression during exercise testing for identification of coronary artery disease.

Within a population of 160 consecutive symptomatic patients who all had undergone catheterization (80 with > or = 1 stenosis > or = 50%), we compared the accuracy of different computerized measurements of the exercise-induced changes in ST-segment: (1) the standard criterion (> or = 0.1 mV flat/downsloping ST depression or > or = 0.15 mV upsloping depression, both 60 ms after the J point); (2) heart rate (HR)-adjusted ST-segment depression (ST/HR index measured at 0, 20, 40, 60, and 80 ms from the J point); (3) the HR-adjusted ST integral (ST/HR integral measured from 0 to 40 ms and from 40 to 80 ms after the J point).

[Regression towards the mean and repeated echocardiographic measurements of the left ventricular mass].

The selection of a group of patients based on a high value of a clinical or biological parameter leads to the finding of a tendency to a reduction of this value when remeasured, known as "regression towards the mean". The amplitude of this phenomenon is greater when the selected subjects are far from normal values and the intra-individual variability of the parameter under consideration is very high. Measurement of left ventricular mass is very affected by this statistical phenomenon.

[Coronary artery disease in hypertensive patients: improvement of the diagnostic value of exercise test by heart rate adjusted ST segment depression].

Unlabelled: Hypertensive patients complaining of chest pain often have a normal coronary angiogram despite a pathological exercise tolerance test. The aim of the present study was to establish whether the prevalence of these "false-positive" tests could be lowered by adjusting ST segment depression for exercise-induced increase in heart rate.

Methods: 60 hypertensive patients, mean age 59 years, with typical or atypical chest pain, underwent both a symptom-limited exercise test and a coronary angiogram within a median period of 1 day.

Effect of regression to the mean in serial echocardiographic measurements of left ventricular mass. Quantification and clinical implications.

When a study sample is selected on the basis of an increased value of a given parameter, subsequent serial measurements are likely to show a decrease in this measured parameter, that is, the "regression to the mean." This statistical phenomenon undoubtedly affects the results of echocardiographic follow-up studies. Its magnitude is linked to that of the intraindividual variability of the measurements.

[Comparative effects of angiotensin converting enzyme inhibitors and calcium antagonists on pulse pressure and blood pressure variability, based on ambulatory measurements in 236 mild to moderate hypertensive patients].

Objective: this retrospective study was aimed: at comparing the effects of angiotensin converting enzyme inhibitors (ACEI) and those of calcium antagonists (CA) on the pulse pressure of mild to moderate hypertensive patients; at assessing whether these effects were associated with some modifications of blood pressure variability or not.

Methods: the ambulatory blood pressure (ABP) recordings of 236 patients who previously entered clinical trials with a mean run-in placebo period of 2 weeks and a mean active treatment phase of 6 weeks (ACEI, n = 115; CA, n = 121) were reviewed. Baseline ABP has been analysed both as a continuous variable and as a categorical one (high when > 139/87 mmHg, low otherwise).