Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Triazinate (Baker's Antifol, NSC 139105) was given to 28 patients as a single agent in the chemotherapy of advanced colerectal carcinoma. The dosage utilized was 250 mg/m2 intravenously, administered daily in three consecutive days. Patients were evaluated at three weeks, six weeks, and then monthly until progression was evident. Various immunologic determinants (i.e., DNCB sensitization, immunoglobulins, recall skin tests, lymphocyte blastogenesis, and circulating lymphocytes, T-cells and B-cells) were obtained prior to treatment and at each re-evaluation. The principal side effects were dermatitis, stomatitis, diarrhea, nausea, somnolence, and leukopenia. There was no discernable effect of Triazinate on the immunologic determinants tested. There was one complete response, and four partial responses, for an objective regression rate of 18%. This study suggests that Triazinate has a definite, though limited, effect on advanced colorectal carcinoma.
 ...
PMID:A phase II study of triazinate (NSC 139105) in advanced colorectal carcinoma. 14 77

The BAF-chromatin remodeling complex, with its mutually exclusive ATPases SMARCA2 and SMARCA4, is essential for the transcriptional activation of numerous genes, including a subset of interferon-stimulated genes (ISGs). Here, we show that C-terminally truncated forms of both SMARCA2 and SMARCA4 accumulate in cells infected with different RNA or DNA viruses. The levels of truncated SMARCA2 or SMARCA4 strongly correlate with the degree of cell damage and death observed after virus infection. The use of a pan-caspase inhibitor and genetically modified cell lines unable to undergo apoptosis revealed that the truncated forms result from the activity of caspases downstream of the activated intrinsic apoptotic pathway. C-terminally cleaved SMARCA2 and SMARCA4 lack potential nuclear localization signals as well as the bromo- and SnAC domain, with the latter two domains believed to be essential for chromatin association and remodeling. Consistent with this belief, C-terminally truncated SMARCA2 was partially relocated to the cytoplasm. However, the remaining nuclear protein was sufficient to induce ISG expression and inhibit the replication of vesicular stomatitis virus and influenza A virus. This suggests that virus-induced apoptosis does not occur at the expense of an intact interferon-mediated antiviral response pathway.IMPORTANCE Efficient induction of interferon-stimulated genes (ISGs) prior to infection is known to effectively convert a cell into an antiviral state, blocking viral replication. Additionally, cells can undergo caspase-mediated apoptosis to control viral infection. Here, we identify SMARCA2 and SMARCA4 to be essential for the efficient induction of ISGs but also to be targeted by cellular caspases downstream of the intrinsic apoptotic pathway. We find that C-terminally cleaved SMARCA2 and SMARCA4 accumulate at late stages of infection, when cell damage already had occurred. Cleavage of the C terminus removes domains important for nuclear localization and chromatin binding of SMARCA2 and SMARCA4. Consequently, the cleaved forms are unable to efficiently accumulate in the cell nucleus. Intriguingly, the remaining nuclear C-terminally truncated SMARCA2 still induced ISG expression, although to lower levels. These data suggest that in virus-infected cells caspase-mediated cell death does not completely inactivate the SMARCA2- and SMARCA4-dependent interferon signaling pathway.
 ...
PMID:Partial Inactivation of the Chromatin Remodelers SMARCA2 and SMARCA4 in Virus-Infected Cells by Caspase-Mediated Cleavage. 2984 89