- A pooled analysis of two phase II trials evaluating metformin plus platinum-based chemotherapy in advanced non-small cell lung cancer. [Journal Article]
- CTCancer Treat Res Commun 2019 May 10; 20:100150
- CONCLUSIONS: Our results confirm the previously shown efficacy and tolerability of metformin in combination with chemotherapy and highlight encouraging activity in key molecular cohorts. Future efforts should build on this work by prospectively studying metformin in these molecular subgroups.
- GATA2-deficient mast cells limit IgE-mediated immediate hypersensitivity reactions in humans. [Journal Article]
- JAJ Allergy Clin Immunol 2019 May 15
- GATA2 deficient patients have a low prevalence of allergic disease resulting from impaired IgE-mediated mast cell activation; thus, GATA2 represents a novel therapeutic target for clinical allergy.
GATA2 deficient patients have a low prevalence of allergic disease resulting from impaired IgE-mediated mast cell activation; thus, GATA2 represents a novel therapeutic target for clinical allergy.
- Transcriptional versus metabolic control of cell fitness during cell competition. [Review]
- SCSemin Cancer Biol 2019 May 15
- The maintenance of tissue homeostasis and health relies on the efficient removal of damaged or otherwise suboptimal cells. One way this is achieved is through cell competition, a fitness quality cont…
The maintenance of tissue homeostasis and health relies on the efficient removal of damaged or otherwise suboptimal cells. One way this is achieved is through cell competition, a fitness quality control mechanism that eliminates cells that are less fit than their neighbours. Through this process, cell competition has been shown to play diverse roles in development and in the adult, including in homeostasis and tumour suppression. However, over the last few years it has also become apparent that certain oncogenic mutations can provide cells with a competitive advantage that promotes their expansion via the elimination of surrounding wild-type cells. Thus, understanding how this process is initiated and regulated will provide important insights with relevance to a number of different research areas. A key question in cell competition is what determines the competitive fitness of a cell. Here, we will review what is known about this question by focussing on two non-mutually exclusive possibilities; first, that the activity of a subset of transcription factors determines competitive fitness, and second, that the outcome of cell competition is determined by the relative cellular metabolic status.
- Medical Malpractice Involving Pulmonary/Critical Care Physicians. [Journal Article]
- ChestChest 2019 May 15
- CONCLUSIONS: Malpractice claims involving PCC physicians were distinct from claims involving internal medicine physicians. Although only a quarter of claims was paid, the indemnity per claim was high among specialties. Specialty-specific prevention strategies must be developed to mitigate both patient harm and provider malpractice risk.
- Three-Dimensional Dose Prediction for Lung IMRT Patients with Deep Neural Networks: Robust Learning from Heterogeneous Beam Configurations. [Journal Article]
- MPMed Phys 2019 May 18
- CONCLUSIONS: The AO model, which does not use beam configuration as input, can still predict dose distributions with reasonable accuracy in high dose regions but introduces large errors in low and medium dose regions for IMRT cases with variable beam numbers and orientations. The proposed AB model outperforms the AO model substantially in low and medium dose regions and slightly in high dose regions by considering beam setup information through a cumulative non-modulated beam's eye view ray-tracing dose distribution. This new model represents a major step forward towards predicting 3D dose distributions in real clinical practice, where beam configuration could vary from patient to patient, from planner to planner, and from institution to institution. This article is protected by copyright. All rights reserved.
- Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease. [Journal Article]
- EHEur Heart J 2019 May 18
- CONCLUSIONS: Metabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclerosis.
- Effects of Ketoconazole on ACTH-Producing and Non-ACTH-Producing Neuroendocrine Tumor Cells. [Journal Article]
- HCHorm Cancer 2019 May 18
- Prolonged remission of hypercortisolism with steroidogenesis inhibitors has been described in patients with ectopic adrenocorticotropic hormone (ACTH) syndrome. The anti-proliferative and pro-apoptot…
Prolonged remission of hypercortisolism with steroidogenesis inhibitors has been described in patients with ectopic adrenocorticotropic hormone (ACTH) syndrome. The anti-proliferative and pro-apoptotic effect of ketoconazole in human cancer cells was previously suggested. The aim of this study was to explore the effects of ketoconazole on ACTH-producing and non-ACTH-producing neuroendocrine tumor (NET) cell lines. The effects of ketoconazole alone, and in combination with somatostatin analogs, were evaluated in two human cell lines: DMS-79 (ectopic ACTH-producing small cell lung carcinoma) and BON-1 (human pancreatic NET). Total DNA measurement, apoptosis, cell cycle, chromogranin A (CgA)/proopiomelanocortin (POMC) expression by qRT-PCR, serotonin, CgA, and ACTH secretion assays were performed. In both cell lines, ketoconazole significantly suppressed cell growth and colony formation in a dose and time-dependent manner. The effect in DMS-79 was primarily cytotoxic, while it was more apoptotic in BON-1 cells. Ketoconazole also induced increase in G0/G1 phase in both cell lines and arrest in phase G2/M of BON-1 cells. Ketoconazole did not affect the secretion of serotonin, CgA, ACTH, or the mRNA expression of CgA and POMC. Decreased serotonin secretion was observed after the combination treatment with pasireotide. These results suggest a direct effect of ketoconazole on cell proliferation, apoptosis, and cell cycle in both ACTH- and non-ACTH-producing NET cells.
- Estimating Lifetime Benefits Associated with Immuno-Oncology Therapies: Challenges and Approaches for Overall Survival Extrapolations. [Journal Article]
- PPharmacoeconomics 2019 May 18
- CONCLUSIONS: Standard parametric models fitted to the initial ATLANTIC DCO generally underestimated longer-term OS, compared with the later DCO. Cure, parametric mixture and response-based landmark models predicted that larger proportions of patients with metastatic non-small cell lung cancer receiving IO treatments may experience long-term survival, which was more in keeping with the observed data. Further research using more mature OS data for IO treatments is needed.
- Investigation of Low-Dose CT Lung Cancer Screening Scan "Over-Range" Issue Using Machine Learning Methods. [Journal Article]
- JDJ Digit Imaging 2019 May 17
- Low-dose computed tomography (CT) lung cancer screening is recommended by the US Preventive Services Task Force for high lung cancer-risk populations. In this study, we investigated an important fact…
Low-dose computed tomography (CT) lung cancer screening is recommended by the US Preventive Services Task Force for high lung cancer-risk populations. In this study, we investigated an important factor affecting the CT dose-the scan length, for this CT exam. A neural network model based on the "UNET" framework was established to segment the lung region in the CT scout images. It was trained initially with 247 chest X-ray images and then with 40 CT scout images. The mean Intersection over Union (IOU) and Dice coefficient were reported to be 0.954 and 0.976, respectively. Lung scan boundaries were determined from this segmentation and compared with the boundaries marked by an expert for 150 validation images, resulting an average 4.7% difference. Seven hundred seventy CT low-dose lung screening exams were retrospectively analyzed with the validated model. The average "desired" scan length was 252 mm with a standard deviation of 28 mm. The average "over-range" was 58.5 mm or 24%. The upper boundary (superior) on average had an "over-range" of 17 mm, and the lower boundary (inferior) on average had an "over-range" of 41 mm. Further analysis of this data showed that the extent of "over-range" was independent of acquisition date, acquisition time, acquisition station, and patient age, but dependent on technologist and patient weight. We concluded that this machine learning method could effectively support quality control on the scan length for CT low-dose screening scans, enabling the eliminations of unnecessary patient dose.
New Search Next
- [The national Network Genomic Medicine (nNGM) : Model for innovative diagnostics and therapy of lung cancer within a public healthcare system]. [Review]
- PPathologe 2019 May 17
- CONCLUSIONS: Interdisciplinary teams are essential for the success of a broad implementation of molecular-pathological diagnostics. nNGM addresses a severe deficit in German lung cancer care and in the future will be expanded to further network centers while meeting the defined quality criteria.