Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of these studies was to examine metastatic potentials of a human colon tumor xenograft (T6) and three different human tumor cell lines (LS174T, HT29 and A549) using the intrasplenic-nude mouse model system (ISMS model system). A further objective was to study the activity of alpha-difluoromethyl-ornithine (DFMO) against primary and metastatic growth of the xenograft and the three cell lines. DFMO is an irreversible inhibitor of ornithine decarboxylase, a rate-limiting step in polyamine biosynthesis. Tumor burdens in the liver of nude mice were observed 6 weeks after the intrasplenic injection with LS174T and 12-14 weeks after intrasplenic injections with T6, HT29 and A549. Most of the mice developed primary tumor growth in the spleens. DFMO showed significant activity against liver metastases but had little or no activity against primary tumor growth in the spleens of the ISMS model and against s.c. growth of the xenograft. The studies demonstrated that the ISMS model system is an excellent system for studying metastatic behavior of human tumors and for studying the antimetastatic activity of experimental drugs.
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PMID:alpha-Difluoromethylornithine inhibits liver metastasis produced by intrasplenic injection of human tumor cells into nude mice. 250 59

The antitumor and antimetastatic effects of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, combined with an inhibitor of S-adenosylmethionine decarboxylase, either methylglyoxal bis(guanylhydrazone) (MGBG) or ethylglyoxal bis(guanylhydrazone) (EGBG), were studied in mice bearing P388 leukemia or Lewis lung carcinoma. Although EGBG is a more specific inhibitor of polyamine biosynthesis than the widely used MGBG, the antitumor effect of the DFMO-EGBG combination on P388 leukemia-bearing mice was less than that of the DFMO-MGBG combination. The prolongation of survival time by the DFMO(1000 mg/kg)-MGBG(25 mg/kg) combination was 2.65-fold, while that of the DFMO(1000 mg/kg)-EGBG(50 mg/kg) combination was 1.34-fold. When mice were fed a polyamine-deficient diet, stronger antitumor effects were exerted; the prolongation of survival time by the DFMO-MGBG and the DFMO-EGBG combinations was 2.89-fold and 2.03-fold, respectively. The antitumor effect of combined use of the two polyamine antimetabolites with mice on normal and polyamine-deficient diets correlated with a decrease of polyamine charge contents in the tumor cells. The above in vivo results were confirmed clearly in the KB cell culture system. The antimetastatic activity of DFMO on Lewis lung carcinoma-bearing mice was strengthened by the addition of MGBG or EGBG. The antimetastatic activity of the DFMO-MGBG or DFMO-EGBG combination did not parallel the polyamine charge contents in the primary tumor and blood.
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PMID:Combined use of alpha-difluoromethylornithine and an inhibitor of S-adenosylmethionine decarboxylase in mice bearing P388 leukemia or Lewis lung carcinoma. 313 38

The effects of DL-alpha-difluoromethylornithine (DFMO), a specific, irreversible inhibitor of ornithine decarboxylase (ODC), on tumors induced in the muscle of C57BL mice by Lewis lung (LL) carcinoma cells and on the development of lung metastases have been investigated. ODC activity and putrescine, spermidine and spermine concentrations were increased both during the early phase of development of the primary LL tumor and in the lung coinciding with the development of metastases. Oral treatment with DFMO (2% aqueous solution as sole drinking fluid, equivalent to 4 g DFMO/kg/day) decreased markedly the ODC activity and the putrescine and spermidine concentrations of the primary tumor, and stimulated S-adenosyl-L-methionine decarboxylase activity. ODC activity and putrescine and spermidine concentrations were similarly markedly reduced in the metastatic lung by DFMO treatment. By comparison with untreated controls, DFMO treatment from day 1 after inoculation resulted in an 81% decrease in tumor size and a 92% reduction of lung metastases by day 20 and prolonged the mean survival time from 20.2 to 28.8 days. The same treatment regimen started 8 days after tumor inoculation resulted in a 52% inhibition of tumor growth and an 82% reduction of lung metastases, and prolonged the mean survival time to 24.9 days. The clear antitumoral effects obtained with DFMO on this animal metastatic cancer indicate its potential value in the treatment of metastases in humans.
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PMID:Treatment of metastatic Lewis lung carcinoma with DL-alpha-difluoromethylornithine. 640 45

We have recently shown that administration of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine (PA) biosynthesis reduces pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice. The present experiments were designed to further explore PA involvement in breast cancer metastasis, using GFP-tagged MDA-MB-435 cells that can be tracked at the single cell level. Administration of DFMO significantly reduced the number of mice with pulmonary metastasis as well as the number of metastases per mouse. Both single-cell and multicellular metastatic deposits were similarly suppressed, thus suggesting that DFMO was inhibiting lung colonization by tumor cells rather than preventing progression of single-cell deposits to overt metastasis. DFMO administration also significantly reduced local recurrences following removal of the primary tumor. Prolongation of DFMO treatment to 14 weeks did not yield a superior antimetastatic effect beyond that provided by a 10-week course of therapy. Discontinuation of DFMO, on the other hand, was associated with local regrowth of the tumors and, possibly, recurrence of pulmonary metastasis. These data provide a rationale for testing the efficacy of anti-PA treatment within the context of adjuvant therapy of breast cancer.
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PMID:Effects of alpha-difluoromethylornithine on local recurrence and pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice. 1285 19