Ga-68-PSMA ligand PET/CT in patients with prostate cancer: How we review and report

Recently, positron emission tomography (PET) imaging using PSMA-ligands has gained high attention as a promising new radiotracer in patients with prostate cancer (PC). Several studies promise accurate staging of primary prostate cancer and restaging after biochemical recurrence with Ga-68-PSMA ligand Positron emission tomography/computed tomography (PET/CT). However, prospective trials and clinical guidelines for this new technique are still missing. Therefore, we summarized our experience with Ga-68-PSMA ligand PET/CT examinations in patients with primary PC and biochemical recurrence. It focuses on the technical and logistical aspects of Ga-68-PSMA ligand PET/CT examination as well as on the specific background for image reading discussing also potential pitfalls. Further, it includes relevant issues on free-text as well as structured reporting used in daily clinical routine

Ga-68-PSMA ligand PET/CT in patients with prostate cancer: How we review and report

Recently, positron emission tomography (PET) imaging using PSMA-ligands has gained high attention as a promising new radiotracer in patients with prostate cancer (PC). Several studies promise accurate staging of primary prostate cancer and restaging after biochemical recurrence with Ga-68-PSMA ligand Positron emission tomography/computed tomography (PET/CT). However, prospective trials and clinical guidelines for this new technique are still missing. Therefore, we summarized our experience with Ga-68-PSMA ligand PET/CT examinations in patients with primary PC and biochemical recurrence. It focuses on the technical and logistical aspects of Ga-68-PSMA ligand PET/CT examination as well as on the specific background for image reading discussing also potential pitfalls. Further, it includes relevant issues on free-text as well as structured reporting used in daily clinical routine

Niacin Reverses Migratory Macrophage Foam Cell Arrest Mediated by oxLDL In Vitro

Introduction: Niacin reduces vascular oxidative stress and down regulates inducible nitric oxide synthase, an enzyme mediating proatherosclerotic effects in part by increasing oxidative stress. Here, we evaluate whether Niacin reverses the redox sensitive migratory arrest of macrophages in response to oxidised(ox) LDL uptake. Material and Methods: Migration of RAW264.7 cells, a murine macrophage cell line and bone marrow derived macrophages from wildtype and iNOS knockout mice was quantified using a modified Boyden chamber. Unstimulated cells or cells preincubated with oxLDL or non-oxidised (n)LDL were treated with Nicotinic acid or Nicotinamide. Nitric oxide, peroxynitrite and ROS production were assessed using electron paramagnetic resonance (ESR). Additionally, flow cytometry analysis of apoptosis, fokal adhesion kinase (FAK), phalloidin, CD36, F4/80 macrophage marker and iNOS gene expression (PCR) were assessed. Results: Migration of Nicotinic acid, Nicotinamide treated cells or unstimulated cells did not differ (P>0.05). oxLDL treatment significantly reduced migration vs. unstimulated cells (p, 0.05). In contrast, migratory arrest in response to oxLDL treatment was reversed by co-incubation with Nicotinic acid and Nicotinamide. The oxLDL-induced peroxynitrite formation in RAW264.7 cells was abolished by Niacin and glutathion (GSH) oxidation was significantly reduced. However, nitric oxide (NO)- and reactive oxygen species (ROS) production induced by oxLDL were not affected by Niacin treatment of RAW264.7 cells. In addition, Nicotinic acid and Nicotinamide reduced actin polymerization, a marker for migratory arrest. Discussion: Our data shows that oxLDL induced inhibition of macrophage migration in vitro can be reversed by Niacin. Furthermore, Niacin reduces peroxynitite formation and improves antioxidant GSH

Niacin Reverses Migratory Macrophage Foam Cell Arrest Mediated by oxLDL In Vitro

Introduction: Niacin reduces vascular oxidative stress and down regulates inducible nitric oxide synthase, an enzyme mediating proatherosclerotic effects in part by increasing oxidative stress. Here, we evaluate whether Niacin reverses the redox sensitive migratory arrest of macrophages in response to oxidised(ox) LDL uptake. Material and Methods: Migration of RAW264.7 cells, a murine macrophage cell line and bone marrow derived macrophages from wildtype and iNOS knockout mice was quantified using a modified Boyden chamber. Unstimulated cells or cells preincubated with oxLDL or non-oxidised (n)LDL were treated with Nicotinic acid or Nicotinamide. Nitric oxide, peroxynitrite and ROS production were assessed using electron paramagnetic resonance (ESR). Additionally, flow cytometry analysis of apoptosis, fokal adhesion kinase (FAK), phalloidin, CD36, F4/80 macrophage marker and iNOS gene expression (PCR) were assessed. Results: Migration of Nicotinic acid, Nicotinamide treated cells or unstimulated cells did not differ (P>0.05). oxLDL treatment significantly reduced migration vs. unstimulated cells (p, 0.05). In contrast, migratory arrest in response to oxLDL treatment was reversed by co-incubation with Nicotinic acid and Nicotinamide. The oxLDL-induced peroxynitrite formation in RAW264.7 cells was abolished by Niacin and glutathion (GSH) oxidation was significantly reduced. However, nitric oxide (NO)- and reactive oxygen species (ROS) production induced by oxLDL were not affected by Niacin treatment of RAW264.7 cells. In addition, Nicotinic acid and Nicotinamide reduced actin polymerization, a marker for migratory arrest. Discussion: Our data shows that oxLDL induced inhibition of macrophage migration in vitro can be reversed by Niacin. Furthermore, Niacin reduces peroxynitite formation and improves antioxidant GSH

Distinguishing between pre- and post-treatment in the speech of patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) causes lung inflammation and airflow blockage leading to a variety of respiratory symptoms; it is also a leading cause of death and affects millions of individuals around the world. Patients often require treatment and hospitalisation, while no cure is currently available. As COPD predominantly affects the respiratory system, speech and non-linguistic vocalisations present a major avenue for measuring the effect of treatment. In this work, we present results on a new COPD dataset of 20 patients, showing that, by employing personalisation through speaker-level feature normalisation, we can distinguish between pre- and post-treatment speech with an unweighted average recall (UAR) of up to 82% in (nested) leave-one-speaker-out cross-validation. We further identify the most important features and link them to pathological voice properties, thus enabling an auditory interpretation of treatment effects. Monitoring tools based on such approaches may help objectivise the clinical status of COPD patients and facilitate personalised treatment plans

Distinguishing between pre- and post-treatment in the speech of patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) causes lung inflammation and airflow blockage leading to a variety of respiratory symptoms; it is also a leading cause of death and affects millions of individuals around the world. Patients often require treatment and hospitalisation, while no cure is currently available. As COPD predominantly affects the respiratory system, speech and non-linguistic vocalisations present a major avenue for measuring the effect of treatment. In this work, we present results on a new COPD dataset of 20 patients, showing that, by employing personalisation through speaker-level feature normalisation, we can distinguish between pre- and post-treatment speech with an unweighted average recall (UAR) of up to 82\,\% in (nested) leave-one-speaker-out cross-validation. We further identify the most important features and link them to pathological voice properties, thus enabling an auditory interpretation of treatment effects. Monitoring tools based on such approaches may help objectivise the clinical status of COPD patients and facilitate personalised treatment plans.Comment: Accepted in INTERSPEECH 202

MiR-502 is the first reported miRNA simultaneously targeting two components of the classical non-homologous end joining (C-NHEJ) in pancreatic cell lines.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Acquired inherited and/or somaticmutations drive its development. In order to prevent the formation of these mutations, precise and immediaterepair of any DNA damage is indispensable. Non-homologous end-joining (NHEJ) is the key mechanism of DNAdouble-strand break repair. Here, we report that miR-502 targets two components in pancreatic cell lines, Ku70and XLF of the C-NHEJ. Interestingly, we also observed an attenuated cell cycle response to gamma ionizingradiation (γ-IR) via diminished phosphorylation of checkpoint kinase 1 (Chk1) on serine 345 in these cell lines.Altogether, pancreatic cells showed increased susceptibility toγ-IR via direct inhibition of DNA double-strandbreak repair and attenuation of the cell cycle response

DNA Polymerase Theta Plays a Critical Role in Pancreatic Cancer Development and Metastasis

Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers worldwide. The occurrence of oncogenic KRAS mutations is considered a signature event in PDAC, leading to genomic instability. The aim of our study was to evaluate the impact of the oncogenic KRAS G12D mutation on the activity of the error-prone alt-EJ repair mechanism, and to investigate the potential role of Polθ in the development of pancreatic cancer. We found that oncogenic KRAS increases the expression of key alt-EJ proteins in a mouse and human PDAC model. Using TLR assay, we also found increased alt-EJ activity in mouse and human cell lines upon the expression of KRAS D12D. The inactivation/impairment of alt-EJ by polymerase theta (Polθ) depletion delays the development of pancreatic cancer and prolongs the survival of experimental mice, though it does not prevent the PDAC development, which leads to full-blown PDAC with disseminated metastasis. Our studies provide a high-value target as a novel therapeutic candidate for the treatment of pancreatic and other cancers. Abstract Pancreatic ductal adenocarcinoma (PDAC), due to its genomic heterogeneity and lack of effective treatment, despite decades of intensive research, will become the second leading cause of cancer-related deaths by 2030. Step-wise acquisition of mutations, due to genomic instability, is considered to drive the development of PDAC; the KRAS mutation occurs in 95 to 100% of human PDAC, and is already detectable in early premalignant lesions designated as pancreatic intraepithelial neoplasia (PanIN). This mutation is possibly the key event leading to genomic instability and PDAC development. Our study aimed to investigate the role of the error-prone DNA double-strand breaks (DSBs) repair pathway, alt-EJ, in the presence of the KRAS G12D mutation in pancreatic cancer development. Our findings show that oncogenic KRAS contributes to increasing the expression of Polθ, Lig3, and Mre11, key components of alt-EJ in both mouse and human PDAC models. We further confirm increased catalytic activity of alt-EJ in a mouse and human model of PDAC bearing the KRAS G12D mutation. Subsequently, we focused on estimating the impact of alt-EJ inactivation by polymerase theta (Polθ) deletion on pancreatic cancer development, and survival in genetically engineered mouse models (GEMMs) and cancer patients. Here, we show that even though Polθ deficiency does not fully prevent the development of pancreatic cancer, it significantly delays the onset of PanIN formation, prolongs the overall survival of experimental mice, and correlates with the overall survival of pancreatic cancer patients in the TCGA database. Our study clearly demonstrates the role of alt-EJ in the development of PDAC, and alt-EJ may be an attractive therapeutic target for pancreatic cancer patients