Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen pediatric patients with brainstem glioma were treated with a combination of interferon-beta, 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitroso ure a hydrochloride (ACNU), and radiation therapy (IAR therapy). All patients received 1-1.5 million IU/day of interferon-beta intravenously for 1 week of each 6-week cycle. In addition, ACNU (2-3 mg/kg) was given on the 2nd day of each cycle. Conventional focal irradiation (1.5-2 Gy/day for 5 days to a total dosage of 40-60 Gy) was administered beginning on day 3. Patients underwent at least two 6-week cycles. Adverse effects included nausea, vomiting, and myelosuppression, but were mild and transient. Response to treatment was evaluated by the reduction in tumor size measured on postcontrast computed tomographic scans and magnetic resonance images. Responses occurred in 10 of 11 patients with the intrinsic type of brainstem glioma, including three complete and seven partial responses. Two of five patients with exophytic type gliomas partially responded. The median survival was 15.7 months, a remarkable improvement over the natural course of this disease. These results indicate that IAR therapy is a useful primary treatment for pediatric patients with brainstem gliomas.
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PMID:Effectiveness of interferon-beta, ACNU, and radiation therapy in pediatric patients with brainstem glioma. 128 18

The efficacy of radiation.MCNU (MR group) or radiation.MCNU.interferon-beta (IMR group) for malignant glioma was studied by a randomized trial at numerous medical facilities. MR group was irradiated with 50-60 Gy and intravenously injected with 2 mg/kg of MCNU on the initial day of irradiation and 6 weeks later. IMR group was also given intravenous administration of interferon-beta at the dose of 2 x 10(6) IU/m2 for 5 serial-days every eight weeks. There was no difference in background between the two groups. The response rate in MR group and IMR group was 44.4% (4/9) and 30.0% (3/10), respectively, showing no significant difference. The resected tumor volume before the start of these regimens seemed to correlate the response to the treatment in both groups. The major toxicity was myelosuppression, especially using MCNU with interferon-beta. These results indicated that this combined therapy is effective for malignant glioma, and should be executed further trials and follow up study.
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PMID:[Randomized study of initial treatment with radiation.MCNU or radiation.MCNU.interferon-beta for malignant glioma. Hiroshima Brain Tumor Study Group]. 240 77

Interferon treatment has been shown to cause myelosuppression in man and in a mouse model. Combinations of interferon-gamma (IFN-gamma) with either interferon-alpha (IFN-alpha) or interferon-beta (IFN-beta) cause the synergistic enhancement of interferons' antiviral, antiproliferative, antitumor, and immunoregulatory activities. Thus, combinations of MuIFN-beta and either natural or recombinant DNA-derived MuIFN-gamma were evaluated for their ability to cause the synergistic enhancement of interferon's myelosuppressive activity. The combinations of interferons were evaluated in vitro in bone-marrow colony-stimulating assays. They were seen to potentiate the in vitro myelosuppressive effect of the interferons. The combinations were evaluated for their in vivo myelosuppressive effect in mice. Treatment with the separate interferons caused a significant reduction in the number of circulating leukocytes, suggesting a potent myelosuppressive effect. However, treatment with the interferons in combination caused an antagonism and led to a myelosuppressive effect which was no greater than that of the interferons alone. The combinations of interferons were employed at concentrations which have been shown to provide substantial potentiation of the antitumor action of the interferons against B-16 melanoma. Thus, the data suggest that combination interferon therapy employing IFN-gamma together with either IFN-alpha or IFN-beta provide a potentiated antitumor activity without increasing the myelosuppressive side effect of the therapy.
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PMID:In vivo myelosuppression by combination interferon treatment: antagonism of MuIFN-gamma and MuIFN-beta myelosuppressive effects. 311 81

The purine nucleoside analogs fludarabine, 2-chlorodeoxyadenosine, and 2'-deoxycoformycin exhibit impressive activity in lymphoproliferative malignancies of adults and children. Their mechanism of action is not clear. Studies have suggested that their use is associated with significant myelosuppression, immunosuppression, and in some circumstances, increased infection with viral and opportunistic pathogens. Because interferons (IFNs) are known to have immunomodulatory activity as well as potent antiproliferative and antiviral activity, we examined whether the chemotherapeutic purine nucleoside analogs alter interferon-beta (IFN-B) gene expression in MG63 in human osteosarcoma cells. Northern blot analysis showed a dose-dependent inhibition of IFN-B mRNA accumulation in response to a known inducer (Poly I-Poly C) all three purine analogs. Hybridization analysis also revealed that inhibition of IFN-beta mRNA accumulation by the purine analogs is not a result of decreased mRNA stability. Further analysis of gene expression by PCR differential display indicated that the effect of the purine analogs was restricted to only a limited number of inducible genes. The data suggest that these molecules alter the signaling process involved in regulating the expression of specific genes, including IFN-beta. These findings predict that the use of purine nucleoside analogs may reduce IFN production in vivo and thereby abrogate host defenses against infectious pathogens.
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PMID:Chemotherapeutic purine analogs alter the level of interferon-beta mRNA induced by poly I-poly C in cultured osteosarcoma cells. 918 62

Combination adjuvant therapy with intravenous dimethyl triazeno imidazole carboxamide (DTIC), 1-[4-amino-2-methyl-5-pyrimidinyl]-methyl-3-[2-chloroethyl]-3-nitrosoure a hydrochloride (ACNU) and vincristine (VCR) and local injection of interferon-beta (IFN-beta) (DAV + IFN-beta therapy) has been widely applied to treat malignant melanoma, and its therapeutic effect is accepted in Japan. Natural killer (NK) activity, CD4+ and CD8+ T cell counts, CD4/CD8 ratio, and white blood cell counts were analyzed before and after DAV + IFN-beta therapy in order to validate its efficacy. After DAV + IFN-beta therapy, the CD4/CD8 ratio was elevated; however, numbers of both CD4+ and CD8+ T cells and NK activity were consecutively depressed. Peripheral lymphocytes were also decreased, possibly by myelosuppression due to the DAV therapy. The posttreatment suppression of NK activity appeared in spite of the administration of IFN-beta. It is suggested that a more effective adjuvant immunomodulator should be introduced to improve the therapeutic effect of the combination adjuvant chemotherapy in malignant melanoma.
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PMID:Changes in immunological parameters after combination adjuvant therapy with intravenous DTIC, ACNU, and VCR, and local injection of IFN-beta (DAV + IFN-beta therapy) into malignant melanoma. 979 42