Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel anti-tumour amphibian oocyte RNase, ONCONASER (ONC), previously known as P-30 Protein, is in the clinical trials. The effect of ONC alone and in combination with lovastatin (LVT), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of mevalonate (MVA) and cholesterol synthesis pathway, in three human tumour cell lines ASPC-1 pancreatic, A-549 lung, and HT-520 lung carcinomas, has been presently studied. A synergism between ONC and LVT in inducing the cytostatic and cytotoxic effects was observed. The cytostatic effect, seen during the early phase of the treatment with this combination of drugs was manifested as prolongation of the cell cycle duration, especially of the G1 phase; cell death was apparent after 72 h of treatment. The synergistic effect of ONC and LVT was also evident in the clonogenicity assays. Both LVT lactone and its in vitro activated beta-hydroxy acid form, alone and in respective combinations with ONC, exerted similar degree of growth suppression. The effects of both forms of LVT (used alone or in combination with ONC) were reversed by MVA, which suggests that HMG-CoA reductase inhibition is a primary mechanism of LVT action. The data indicate that the LVT lactone can be activated intracellularly by tumour cells studied, and that the combination of ONC with LVT can produce significantly enhanced anti-tumour activities.
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PMID:Synergism between a novel amphibian oocyte ribonuclease and lovastatin in inducing cytostatic and cytotoxic effects in human lung and pancreatic carcinoma cell lines. 150 3

Tryptophan hydroxylase (TPH) is the rate limiting enzyme in serotonin biosynthesis [D.G. Grahame-Smith, Tryptophan hydroxylation in brain, Biochem. Biophys. Res. Commun. 16 (1964) 586-592 [19]]. As such, the TPH gene is a likely target for modulation of serotonergic function, which has been associated with several psychiatric disorders [E.C. Azmitia, P.M. Whitaker-Azmitia, Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system, J. Clin. Psychiatry 52 (12, Suppl.) (1991) 4-16 [1]; R.P. Hart, R. Yang, L.A. Riley., T.L. Green, Post-transcriptional control of tryptophan hydroxylase gene expression in rat brain stem and pineal gland, Mol. Cell. Neurosci. 2 (1991) 71-77 [20]; M.J. Owens, C.B. Numeroff, Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter, Clin. Chem. 40 (1994) 288-295 [24]]. Unfortunately, it has been technically difficult to measure TPH mRNA levels in central serotonergic neurons due to its low levels. For example, detection with ribonuclease protection assays requires pooling of 5-10 dissected brainstems [M.C. Darmon, B. Guibert, V. Leviel, M. Ehret, M. Maitre, J. Mallet, Sequence of two mRNAs encoding active rat tryptophan hydroxylase, J. Neurochem. 51 (1988) 312-316 [15]; B.L. Jacobs, E.C. Azmitia, Structure and function of the brain serotonin system, Physiol. Rev. 72 (1992) 165-229 [21]]. This protocol describes the use of competitive RT-PCR to measure TPH mRNA levels from rat brain. First described in 1988, competitive RT-PCR has become an accepted method of measuring RNA abundance [M. Clementi, S. Menzo, P. Bagnarelli, A. Manzin, A. Valenza, P.E. Varaldo, Quantitative PCR and RT-PCR in virology, PCR Methods Appl. 2 (1994) 191-196 [12]; N.C.P. Cross, Quantitative PCR techniques and applications, Br. J. Haematol. 89 (1995) 693-697 [14]; K.P. Foley, M.W. Leonard, J.D. Engel, Quantitation of RNA using the polymerase chain reaction, Trends Genet. 9 (1993) 380-385 [17]; P.D. Siebert, J.W. Larrick, Competitive PCR, Nature 359 (1992) 558 [27]]. Competitive RT-PCR uses co-amplification with a known quantity of an in vitro transcribed RNA which amplifies using the same primers and thus competes for reactants with the product of interest. As the two products amplify with the same efficiency, the relative abundance of the two amplification products remains constant, and thus can be used to determine initial tissue TPH mRNA levels [G. Gilliland, S. Perrin, K. Blanchard, H.F. Bunn, Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction, Proc. Natl. Acad. Sci. U.S.A. 87 (1990) 2725-2729 [18]; A.M. Wang, M. V. Doyle, D.F. Mark, Quantitation of mRNA by the polymerase chain reaction, Proc. Natl. Acad. Sci. U.S.A. 86 (1989) 9717-9721 [31]]. We first demonstrate equivalent results between RNA slot blots and competitive RT-PCR using the CA77 thyroid C cell line [M.S. Clark, A. F. Russo, Tissue-specific glucocorticoid regulation of tryptophan hydroxylase mRNA levels, Mol. Brain Res. 48 (1997) 346-354 [9]]. We then describe the use of competitive RT-PCR to measure TPH mRNA levels in RNA isolated from rat brain poly-A+ RNA.
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PMID:Measurement of tryptophan hydroxylase mRNA levels by competitive RT-PCR. 963 Jun 72

A novel amphibian oocyte RNase, ONCONASE(R) (ONC), has been previously shown to have synergistic tumor cell growth inhibitory activity when combined with tamoxifen (TMX) and/or trifluoperazine (TFP) in human ASPC-1 pancreatic and A-549 lung carcinoma cells, respectively. It has recently been reported that several drugs known to bind to the intracellular antiestrogen binding site (AEBS)/histamine (H(IC)) receptors, including tricyclic (amitriptyline, AMT) and non-tricyclic (fluoxetine, FLX) antidepressants, TMX, phenothiazines and the prototype H(IC)-binder DPPE, can stimulate the in vitro and in vivo growth of rodent tumor cells, while having a normal cell growth inhibitory activity, as reflected by the inhibition of the DNA synthesis. It has been presently shown that while at the clinically relevant concentrations some of these H(IC)-binding drugs mildly stimulated (up to 15%) the cell growth in the human lines studied when used as single agents, in most instances this stimulation did not exceed 10% above the control values. When used in combination with ONC, neither of these H(IC)-binding drugs demonstrated any apparent synergistic activity as judged from the ED50 values. However, the combinations of DPPE+TFP and AMT+TFP, in both the ASPC-1 and COLO 320DM lines, demonstrated a significant cell growth inhibition, while there was no difference between the effects of AMT alone and the AMT+TFP combination in the U87MG line. The most effective cell growth inhibition was obtained when ONC was combined with DPPE+TFP and/or AMT+TFP, as reflected by the significantly decreased ED50 values.
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PMID:Human tumor-cell growth modulatory effects of the aebs/hic-binding drugs used as single agents and in combination with a novel amphibian oocyte rnase. 2157 30