Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.4 (RNase H)
 2,751 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood mononuclear cells (PBMNC) from 23 healthy subjects and 39 patients with B-cell chronic leukaemia (B-CLL) were assayed for ribonuclease H activity using as substrate the filter-immobilized synthetic homopolymer hybrid 3H-poly(rA):poly(dT). In 69% of the leukaemia patients examined enzyme activities were above those estimated in cells from the healthy controls. The mean enzyme levels for the normal and the leukaemic samples group were (per cent substrate hydrolysis): 8.1 +/- 8.9 and 58.7 +/- 40.8, respectively, their difference being statistically highly significant (P less than 0.0001). This result does not represent homogeneity within the cells but is due to a subclass of cells within the leukaemic clone containing the enzyme, thus contributing through pool size fluctuation to the wide variations of enzyme activity observed among the patients. These cells containing high activity could not be identified with either the prolymphocytes or the large lymphocytes. The activity of ribonuclease H in the examined CLL patients correlated with disease stage (Binet) (P = 0.011) and appeared to serve as a sensitive indicator of disease progression when compared with a number of other known prognostic parameters.
 ...
PMID:Activity of ribonuclease H in cells of chronic B-lymphocytic leukaemia: correlation with clinical stage. 284 80

Antisense oligonucleotides have been evaluated as antineoplastic agents in a series of clinical trials, with mixed results. However, phase III trials incorporating G3139, a phosphorothioate oligomer targeted to the initiation codon region of the bcl-2 mRNA, have recently been completed in advanced melanoma, myeloma, and chronic lymphocytic leukemia (CLL). This article discusses the mechanism of the antisense effect and its dependence on the cellular internalization of oligonucleotides and the activity of RNase H. It also describes the properties, specific and nonspecific, of phosphorothioate oligonucleotides, the predominant species in current clinical trials, and discusses pharmacokinetic data obtained from earlier phase I and II trials employing these molecules. While the application of antisense technology to the treatment of human cancer is conceptually straightforward, in practice there are many complicated, mechanistically based questions that must be considered.
 ...
PMID:Antisense strategies for oncogene inactivation. 1633 22