Biologics Safety Assessment, 2 Acute Toxicology, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486, USA.
Published: May 2006
AI Article Synopsis
Article Abstract
Although there is a WHO guidance for a limit on residual DNA for parenterally administered vaccines produced on continuous cell lines, there is no corresponding guidance for oral vaccines. To help determine an oral limit, we performed a study of Vero cell DNA uptake in rats, in which the relative uptake and persistence of Vero cell DNA administered orally was compared to its uptake when delivered intramuscularly (IM). The results of this study allowed the generation of an empirically derived IM versus oral factor (10(6)) representing the relative inefficiency of DNA uptake by oral administration. This factor was then applied to the WHO recommended parenteral limit of 10 ng/dose to determine a corresponding upper limit on the level of residual Vero cell DNA for an oral vaccine of 10 mg. As a conservative approach, this empirically determined limit was reduced 100-fold to 100 microg. Thus, the results of this animal study, together with additional evidence in the literature, support a residual DNA safety limit of 100 microg per dose for an oral vaccine produced on a continuous cell line.
John P. Hussman Institute for Human Genomics, University of Miami, FL; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, FL.
Heterozygosity for loss-of-function alleles of the genes encoding the four subunits of succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD), as well as the SDHAF2 assembly factor predispose affected individuals to pheochromocytoma and paraganglioma (PPGL), two rare neuroendocrine tumors that arise from neural crest-derived paraganglia. Tumorigenesis results from loss of the remaining functional SDHx gene copy, leading to a cell with no functional SDH and a defective tricarboxylic acid (TCA) cycle. It is believed that the subsequent accumulation of succinate competitively inhibits multiple dioxygenase enzymes that normally suppress hypoxic signaling and demethylate histones and DNA, ultimately leading to increased expression of genes involved in angiogenesis and cell proliferation.
Background And Objective: Mitochondria are important organelles functioning in metabolic processes, inflammatory response and neurological disorders. Migraines are chronic and paroxysmal neurological disorders characterized by recurrent episodes of severe headache and other neurological symptoms. We explored whether mitochondria may be genetically and/or causally associated with migraine.
Introduction: Assessment of circulating tumor DNA (ctDNA) as means to monitor disease activity in translocation-associated tumors has become very popular in clinical practice. However, there are still few studies on its clinical application to date. Our study evaluates the clinical applicability of ctDNA as a biomarker for monitoring minimal residual disease (MRD) in patients with translocation-associated sarcomas.
Department of Obstetrics and Gynecology, National Clinical Research Centre for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background: Epithelial ovarian cancer (EOC) is a lethal form of gynecological malignancy. Some EOC patients experience relapse after standard primary debulking surgery (PDS) and adjuvant chemotherapy (ACT). Identifying molecular residual disease (MRD) by circulating tumor DNA (ctDNA) detection can timely signal the potential for relapse.
