Disease relevance of Ornidyl

• Hypertrophy caused by triiodothyronine was not prevented by DFMO [1].
• Treatment of recurrent gliomas with eflornithine [2].
• Ninety-eight patients were entered in the eflornithine arm; 80 patients (36 glioblastoma multiforme patients and 44 anaplastic glioma patients) were assessable for response [2].
• 26 patients with arseno-resistant Trypanosoma brucei gambiense trypanosomiasis were treated with difluoromethylornithine (eflornithine), an inhibitor of ornithine decarboxylase, given intravenously, then orally [3].
• Efficacy and toxicity of eflornithine for treatment of Trypanosoma brucei gambiense sleeping sickness [4].

Psychiatry related information on Ornidyl

• RESULTS: Predictable shifts in auditory thresholds occurred following administration of eflornithine [5].
• While having no influence per se on pain threshold, DFMO significantly inhibited the analgesic activity of morphine (15 mg/kg i.p.), this effect being obtained when brain ODC activity was reduced by at least 80% [6].
• Use of a self-assessment questionnaire to assess the effect of study treatment on 6 aspects of patient well-being showed that eflornithine reduced the mean level of overall discomfort and bother by 33 versus 15% in placebo recipients [7].

High impact information on Ornidyl

• There appear to be both ODC-dependent and ODC-independent processes contributing to the subcellular mechanisms associated with growth, which must be considered in the potential laboratory and clinical use of DFMO [1].
• Mechanisms of antitrypanosomal action of these drugs are mostly unknown, except for eflornithine, which is a suicide inhibitor of ornithine decarboxylase [8].
• METHODS: Noncancerous, preimmortal breast epithelial cells derived from a patient with LFS were treated for 3 months with nontoxic concentrations of the chemopreventive agents oltipraz, difluoromethylornithine, tamoxifen, and retinoic acid or with two different telomerase inhibitors [9].
• BACKGROUND: Oral eflornithine in combination with intravenous mitoguazone (methylbisguanylhydrazone) has shown activity against recurrent anaplastic gliomas [2].
• PURPOSE: This study compared the antitumor activity of oral eflornithine with that of oral eflornithine combined with intravenous mitoguazone in the treatment of patients with recurrent or progressive glioblastoma multiforme as well as nonglioblastoma anaplastic gliomas [2].

Chemical compound and disease context of Ornidyl

• Efficacy of combinations of difluoromethylornithine and bleomycin in a mouse model of central nervous system African trypanosomiasis [10].
• Inhibition of polyamine biosynthesis with alpha-difluoromethylornithine (DFMO) has been shown to inhibit proliferation of breast cancer cells although its mechanism of action has not been fully elucidated [11].
• Reduction of difluoromethylornithine-induced thrombocytopenia in rats with ornithine while maintaining antitumor activity [12].
• Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos [13].
• Nine patients with hematological malignancies were treated with difluoromethylornithine and methylglyoxal bis(guanylhydrazone) [14].

Biological context of Ornidyl

• Treatment of mouse lymphoma S49 cells with D,L-alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, depleted cellular polyamine levels and stopped cell growth [15].
• A pBR322 cDNA library was prepared from poly(A)+ RNA isolated from difluoromethylornithine-resistant cells, and the library was probed with [32P]cDNA representing mRNA sequences from resistant or parental (sensitive) cells [16].
• Under the influence of a selective irreversible inhibitor of ornithine decarboxylase (ODC), DL-alpha-difluoromethylornithine (DFMO), early hematopoiesis was enhanced [17].
• DFMO was also found to suppress cell proliferation in, and the growth of, the transplantable colon cancers [18].
• Although the rate of apoptosis in papillomas was unaffected by acute DFMO treatment, tumor cell proliferation was rapidly decreased after drug treatment [19].

Anatomical context of Ornidyl

• Repair of duodenal mucosa after stress was extensively delayed by administering 500 mg/kg DL-alpha-difluoromethylornithine (DFMO) IP [20].
• In the presence of DFMO, the HA-V14-RhoA cells lost stress fibers and gained the appearance of HA-N19-RhoA cells or wild-type cells treated with DFMO [21].
• RESULTS: DFMO caused a significant decrease in Rho levels in the cytoplasm and membranes of IEC-6 cells [21].
• This DFMO concentration did not inhibit colony formation in either cell line, but did reduce the growth rate of both cultures [22].
• Polyamine depletion using DL-alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, has been shown to suppress cell growth in a variety of settings, including those of tumor and lymphocyte proliferation [23].

Associations of Ornidyl with other chemical compounds

• The effect of oPRL and oGH was blocked by alpha-difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase, the rate-limiting enzyme of polyamine biosynthesis [24].
• An inhibitor of ornithine decarboxylase, difluoromethylornithine (DFMO), and two inhibitors of prostaglandin biosynthesis, piroxicam and menhaden fish oil, were examined for their effect on intestinal tumorigenesis in male Sprague-Dawley rats fed a 5% fat semisynthetic diet [25].
• Addition of putrescine (0.1-2.5 mM) to DFMO-treated cells repleted cellular PA levels and restored growth to approximately 80% of control in both cell lines [26].
• The stimulation of tyrosinase (EC 1.10.3.1) activity and melanin formation by DFMO was closely associated with intracellular depletion of putrescine and spermidine developed in response to the drug [27].
• In other tissues studied, i.e., brain, skeletal and cardiac muscle, liver, kidney, and spleen, a preceding treatment with DFMO had no effect on the accumulation of subsequently injected MGBG [28].

Gene context of Ornidyl

• Western blot analysis revealed that treatment of RASMC with NO or DFMO leads to activation of p42/p44 MAPK and induction of p21(waf1/cip1) [29].
• Inhibition of the MAPK pathway with PD98059 or U0126 blocked the DFMO-induced induction of p21 and the reduction of cdk-2 protein [11].
• We found that DFMO caused a p53-independent increase in p21 and its association with cyclin-dependent kinase (cdk)-2 and decreased cdk-2 protein as well as its phosphorylation on Thr160 [11].
• MDA-MB-435 cells treated with PD98059 or U0126 in the presence and absence of DFMO exhibited a marked increase in the expression of p27 and its association with cdk-2, a decrease in phosphorylation of cdk-2 on Thr160, and a decrease in cyclin E expression [11].
• When K14-MEK mice were given alpha-difluoromethylornithine (DFMO), a suicide inactivator of ODC, in the drinking water from birth, there was a dramatic delay in the onset of tumor growth ( approximately 6 weeks), and only 25% of DFMO-treated mice developed tumors by 15 weeks of age [30].

Analytical, diagnostic and therapeutic context of Ornidyl

• CONCLUSION: This study suggests that eflornithine alone is an effective palliative therapy for recurrent anaplastic gliomas [2].
• Chemoprevention of mouse colon tumors with difluoromethylornithine during and after carcinogen treatment [31].
• The steady state level of DFMO achieved at the highest dose (3 g/m2) were found to be within the range needed for inhibition of ornithine decarboxylase in cell-culture systems as well as for the inhibitory activity against various human tumors in vitro [32].
• These promising, albeit preliminary, results of difluoromethylornithine therapy, even in patients with central nervous system involvement, indicate that extended clinical trials are warranted to determine the optimal dosage regimen in patients with early- and late-stage disease [33].
• The experimental group was given 0.5% DFMO in their drinking water, while the control group was given tap water [34].

References