Search

Alexandra Capellini,1,* Matthew Williams,1,* Kenan Onel,1– 3 Kuan-Lin Huang1– 3 1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, USA, New York, NY, 10029, USA; 2Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, USA, New York, NY, 10029, USA; 3Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, USA, New York, NY, 10029, USA*These authors contributed equally to this workCorrespondence: Kenan Onel; Kuan-Lin HuangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, Box 1498, New York, NY, 10029, USATel +1 212-824-6134Email kenan.onel@mssm.edu; kuan-lin.huang@mssm.eduAbstract: The canonical model for hereditary cancer predisposition is a cancer predisposition gene (CPG) that drives either one or both of two fundamental hallmarks of cancer, defective genomic integrity and deregulated cell proliferation, ultimately resulting in the accumulation of mutations within cells. Thus, the genes most commonly associated with cancer-predisposing genetic syndromes are tumor suppressor genes that regulate DNA repair (eg, BRCA1, BRCA2, MMR genes) and/or cell cycle (eg, APC, RB1). In recent years, however, the spectrum of high-penetrance CPGs has expanded considerably to include genes in non-canonical pathways such as oncogenic signaling, metabolism, and protein translation. We propose here that, given the variety of pathways that may ultimately affect genome integrity and cell proliferation, the model of cancer genetic predisposition needs to be expanded to account for diverse mechanisms. This synthesis calls for modeling and multi-omic studies applying novel experimental and computational approaches to understand cancer genetic predisposition.Keywords: cancer, genetics, predisposition, multi-omics, genomics, oncogenesis

Cheng-Yi Wang,1,* Yin-Lan Hu,2,* Ya-Hui Wang,3 Cheng-Hsin Chen,1 Chih-Cheng Lai,4 Kun-Lun Huang51Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu-jen Catholic University, New Taipei City, Taiwan; 2Department of Dentistry, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 3Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 4Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan; 5Division of Pulmonary Medicine, Tri-service General Hospital, Institute of Undersea and Hyperbaric Medicine, National Defense Medical Center, Taipei, Taiwan*These authors contributed equally to this workBackground: Latent tuberculosis infection (LTBI) is a precursor of active tuberculosis diseases and an important issue in the United States and worldwide. The association between vitamin D deficiency and LTBI is poorly understood.Methods: From 2011 to 2012, the National Health and Nutrition Examination Survey (NHANES) assessed LTBI (according to tuberculin skin testing and QuantiFERON®,-TB Gold In-Tube) and measured serum levels of vitamin D. We evaluated the association between LTBI and vitamin D using multivariate logistic regression models adjusted for known confounders.Results: The LTBI group had a lower 25-hydroxyvitamin D [25(OH)D] level than the non-LTBI group (p=0.0012). The adjusted risk of LTBI was significantly higher among participants with serum 25(OH)D levels

Baicalin is a flavonoid present in many traditional Chinese medicines. A number of studies show that baicalin has anti-inflammatory actions and protects against a variety of tissue and organ injuries. The effect of baicalin in lipopolysaccharide (LPS)-induced acute lung injury is not well studied. In this study, typically acute lung injury was induced in rat by intratracheal injection of LPS, which increased lactate dehydrogenase activity and protein content in bronchoalveolar lavage fluid, wet/dry lung weight ratio, Evan's blue dye leakage, and neutrophil infiltration. Baicalin (20 mg/kg) was administrated 1 hour before or 30 min after LPS injection. Both pre and post-treatment with baicalin attenuated the increase of these parameters and improved histological finding. Our results suggest that baicalin has a therapeutic effect on LPS-induced acute lung injury. [ABSTRACT FROM AUTHOR]

Study Objectives: We compared the clinical characteristics and imaging findings between immunocompetent and immunocompromised patients in whom pulmonary cryptococcosis had been diagnosed to define the role of serum cryptococcal antigen (sCRAG) and radiographs during a follow-up period of up to 1 year.Design: Retrospective cohort study.Setting: University hospital.Patients: The clinical records, chest radiographs, and CT scan findings of 13 immunocompetent and 16 immunocompromised patients with a diagnosis based on cerebrospinal fluid (CSF) culture, sCRAG titers, and cytologic or histologic confirmation of the presence of pulmonary cryptococcosis were reviewed during the course of the study. Two thoracic radiologists reviewed chest radiographs and CT scans for morphologic characteristics and the distribution of parenchymal abnormalities, and a final reading was reached by consensus. The correlation between serial radiographs and sCRAG titers was examined in 9 immunocompetent and 10 immunocompromised patients.Measurements: Serum or CSF cryptococcal antigen.Results: The most common clinical symptom was cough, which was present in 24 patients (82.8%). Pulmonary nodules were the most frequent radiologic abnormality. Cavitation within nodules and parenchymal consolidation were significantly less common in immunocompetent patients compared to immunocompromised patients (p = 0.02 and p = 0.05, respectively). Immunocompromised patients tended to have a larger extent of pulmonary involvement than immunocompetent patients, the changes seen on their serial radiographs were more variable, and their corresponding sCRAG titers were higher (> 1:256). In the immunocompetent patients, the radiographic characteristics of lesions usually improved with a corresponding decrease in sCRAG titers over time.Conclusions: Our study suggests that pulmonary cryptococcosis usually follows a benign clinical course in immunocompetent patients. Immunocompromised patients often undergo an evolution to cavitary lesions that represent a more aggressive disease nature. Serial radiographic changes and changes in sCRAG titers reliably reflect disease progression and the response to therapy. [ABSTRACT FROM AUTHOR]