Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following the notification in the USA and England of four cases of Creutzfeldt-Jacob disease (MCJ) in patients previously treated with hGH, an epidemiological inquiry has been done in France to set up a clinical evaluation of all patients treated from 1959 to 1985. 1698 patients were registered for treatment. Current information (less than three months old) was obtained for 1622 patients (95.5%). Death was reported in 32 patients (2.0%), one is possibly related to a viral infection (malignant lymphoma), but none could be related to MCJ. Accidents were observed in 213 living patients (13.1%). Among them, 4 cases were classified as possibly related to a viral infection: acute lymphoid leukaemia, polyradiculoneuritis associated with hepatitis, acute encephalitis (2 cases). Even though the clinical symptomatology is not consistent with MCJ, a relationship with hGH therapy could not be completely excluded. Finally, six patients undertreatment developed malignancies. During the three last years, the question of side effects of hGH therapy has been raised in the literature two times running: risk of MCJ and risk of leukaemia. Then, the question of the long term vigilance of all treated patients with hGH deficiency should be done.
 ...
PMID:[Evaluation of risks related to human growth hormone (hGH) treatment. Results of an epidemiologic survey conducted in France of patients treated from 1959 to 1985]. 267 93

An epidemiological inquiry has been done in France after the notification in the USA and England of four cases of Creutzfeldt-Jakob disease in patients previously treated with hGH. Between 1959, when hGH treatment in France was started, and August 1985, the date the survey began, 1698 patients were registered for treatment. Current information (less than three months old) was obtained for 1620 patients (95.4%). Death was reported in 31 patients, but none could be related to Creutzfeldt-Jakob or similar disease. Pathological events were observed in 213 living patients (13.1%). Among them, four were diseases classified as possibly related to a viral infection. The first case had acute lymphoid leukaemia; the second case had polyradiculoneuritis associated with hepatitis. In both cases the disease resolved completely. Two other patients had acute encephalitis which started less than two years after the onset of treatment and which resolved spontaneously. Even though the acute evolution and the spontaneous clinical recovery are not consistent with Creutzfeldt-Jakob disease, a relationship with hGH therapy could not be completely excluded. Finally, five treated children had later malignancies which raises the question of the long-term secondary effects of hGH upon cellular proliferation.
 ...
PMID:Human pituitary growth hormone (hGH) and Creutzfeldt-Jakob disease: results of an epidemiological survey in France, 1986. 304 52

Replication fork stability during DNA replication is vital for maintenance of genomic stability and suppression of cancer development in mammals. ATR (ataxia-telangiectasia mutated [ATM] and RAD3-related) is a master regulatory kinase that activates the replication stress response to overcome replication barriers. Although many downstream effectors of ATR have been established, the upstream regulators of ATR and the effect of such regulation on liver cancer remain unclear. The ubiquitin conjugase BRUCE (BIR Repeat containing Ubiquitin-Conjugating Enzyme) is a guardian of chromosome integrity and activator of ATM signaling, which promotes DNA double-strand break repair through homologous recombination. Here we demonstrate the functions for BRUCE in ATR activation in vitro and liver tumor suppression in vivo. BRUCE is recruited to induced DNA damage sites. Depletion of BRUCE inhibited multiple ATR-dependent signaling events during replication stress, including activation of ATR itself, phosphorylation of its downstream targets CHK1 and RPA, and the mono-ubiquitination of FANCD2. Consequently, BRUCE deficiency resulted in stalled DNA replication forks and increased firing of new replication origins. The in vivo impact of BRUCE loss on liver tumorigenesis was determined using the hepatocellular carcinoma model induced by genotoxin diethylnitrosamine. Liver-specific knockout of murine Bruce impaired ATR activation and exacerbated inflammation, fibrosis and hepatocellular carcinoma, which exhibited a trabecular architecture, closely resembling human hepatocellular carcinoma (HCC). In humans, the clinical relevance of BRUCE down-regulation in liver disease was found in hepatitis, cirrhosis, and HCC specimens, and deleterious somatic mutations of the Bruce gene was found in human hepatocellular carcinoma in the Cancer Genome Atlas database. Conclusion: These findings establish a BRUCE-ATR signaling axis in accurate DNA replication and suppression of liver cancer in mice and humans and provides a clinically relevant HCC mouse model.
 ...
PMID:The BRUCE-ATR Signaling Axis Is Required for Accurate DNA Replication and Suppression of Liver Cancer Development. 3069 43