Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Putrescine is a potential scanning agent for metastases of prostatic carcinoma. We examined the in vivo uptake of [14C]-putrescine by the Dunning R3327H Copenhagen rat prostatic tumor and by other tissues, and conclude that: The uptake of [14C]-putrescine by the tumor was higher than that of the normal dorsolateral prostate, but similar to that of the ventral prostate. Tumor accumulation of [14C]-putrescine was enhanced 38% in intact and 45% in castrated animals by pretreatment with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor. Further enhancement of tumor uptake (94% in intact and 201% in castrated animals) was achieved by combining DFMO pretreatment with androgen stimulation. Oral administration of methyl-glyoxal bis (guanylhydrazone) (MGBG) increased intestinal uptake of [14C]-putrescine, while oral administration of unlabeled spermine and putrescine decreased it. Dexamethasone decreased the uptake of [14C]-putrescine by the spleen and intestine, but also reduced the prostatic uptake to a considerable extent. These observations are useful for the design of a putrescine-based scan for metastases of prostatic carcinoma.
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PMID:alpha-Difluoromethylornithine enhancement of 14C-putrescine uptake by an androgen-dependent prostatic tumor. 309 95

Thirty-six patients with adenocarcinoma or epidermoid carcinoma of the esophagus were entered into a phase II trial evaluating the combination of cisplatin 100 mg/m2 intravenously (IV) day 2, vinblastine 1.6 mg/m2 IV days 1 to 4, and mitoguazone (MGBG) 500 mg/m2 IV days 1 and 8. Twenty-nine patients (group A) were newly diagnosed with local-regional disease only and were candidates for transhiatal esophagectomy (THE). These patients received two courses of chemotherapy at 3-week intervals prior to surgery. Response was assessed by measuring changes in the primary tumor length and depth on serial biphasic contrast esophagrams and comparing this result with tumor measurements obtained from the surgical specimen. Complete (CR) and partial responders (PR) received three additional postoperative cycles. Seven patients had recurrent or metastatic disease (group B) and were treated every 4 weeks until disease progression. Of 34 patients evaluable for response, there was one pathologically confirmed CR and 15 PRs (47%). This consisted of 12 of 27 (44%) group A patients (seven of 11 epidermoid, five of 16 adenocarcinoma) and four of seven (57%) group B patients (two of four epidermoid, two of three adenocarcinoma). Toxicity included leukopenia in one third of treatment courses and thrombocytopenia in 21%. Nausea and vomiting occurred in 60% of patients, diarrhea in 18%, transient nephrotoxicity in 18%, peripheral neuropathy in 12%, and ototoxicity in 3%. Twenty-five group A patients underwent resection. Four chemotherapy nonresponders (NR) and one PR had known disease left at surgery; all others (80%) had gross total removal of their disease. The median survival time (MST) of the 29 group A patients was 14 months, with 21% alive at 36 months. The MST of group A chemotherapy responders was 15 months compared with 9 months for NRs (P = .032). Initial sites of recurrence in 14 patients were local-regional in six, distant only in six, both local-regional and distant in two. This regimen, administered in maximally tolerated doses, was active in epidermoid and adenocarcinoma histologies, recurrent disease and newly diagnosed patients. However, nearly all responses were PRs and the MST of resected patients was similar to a prior series of patients treated with esophagectomy alone. Observations from this pilot trial and those of others have led to a follow-up study, in progress, evaluating intensive preoperative chemotherapy and concurrent radiation therapy (RT).
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PMID:Cisplatin, vinblastine, and mitoguazone chemotherapy for epidermoid and adenocarcinoma of the esophagus. 362 44

Methylglyoxal-bis(guanylhydrazone) (MGBG), an inhibitor of polyamine synthesis, was administered to 35 patients with hormone-resistant advanced adenocarcinoma of the prostate in doses of 500 or 600 mg/m2 per week intravenously. Of 31 patients with bidimensional measurable soft-tissue lesions, 25 had an adequate trial, defined as four or more doses. Six (24%; 95% confidence limits, 8% to 32%) patients achieved a partial remission (greater than or equal to 50% reduction in tumor size) in soft-tissue disease. Response was noted to start after one to two doses and persisted for a median of three months (range, 1 to 4 months). Toxicity was tolerable, and significant myelosuppression was not observed. The lack of response in osseous metastases may be secondary to the short duration of remission or to the presence or inducibility of the enzyme ornithine decarboxylase in bone. Since some animal prostatic cancer tumor models are sensitive to cytotoxic drugs that produce polyamine inhibition, clinical trials of MGBG combined with other inhibitors of the polyamine pathway should be explored.
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PMID:Methylglyoxal-bis(guanylhydrazone) in hormone-resistant adenocarcinoma of the prostate. 396 52

alpha-Difluoromethylornithine (DFMO) and methylglyoxal bis-(guanylhydrazone) (MGBG) were tested against a murine renal adenocarcinoma, because polyamines are necessary for neoplastic cell growth and because human renal adenocarcinomas contain higher levels of spermidine than do normal renal cells; MGBG inhibits spermidine synthesis and has some activity against human renal tumors; DFMO irreversibly inhibits ornithine decarboxylase, the first rate-limiting enzyme controlling polyamine biosynthesis; and DFMO promotes intracellular accumulation of MGBG in experimental tumor models and human leukemia. DFMO (2%) in drinking water, MGBG (15 mg/kg i.p.), or a combination of DFMO and MGBG was administered daily to BALB/c mice (n = 80) with intrarenal transplants of renal adenocarcinoma cells. At 28 days, renal carcinomas weighed 64 and 73% less, respectively, in DFMO- and DFMO-MGBG-treated mice than in control animals (p less than 0.01). MGBG alone had no antigrowth effect. DFMO-MGBG reduced the total metastatic index (total number of metastases/total number of animals) to 1.2 versus 3.6 in control animals (p less than 0.01) and increased survival by 12.3 +/- 1.5 (S.E.) days, from 30.8 to 42.5 days (p less than 0.05). Compared with control, DFMO-, or MGBG-treated animals, DFMO-MGBG exposure reduced tumor growth and the number of metastases, prevented metastases in some animals (47%), and increased survival of mice bearing renal adenocarcinomas. DFMO also appeared to selectively increase the uptake of [14C]MGBG by tumor tissue, which may help to explain the enhanced synergistic antigrowth effect of DFMO and MGBG against this murine renal adenocarcinoma.
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PMID:Effects of alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) on the growth of experimental renal adenocarcinoma in mice. 643 12

In a phase II study of methyl-glyoxal bis-guanylhydrazone (methyl-GAG) in patients with bi-dimensionally measurable metastases of renal cell cancer, 30 patients were given 500 mg/m2 weekly for at least 4 treatment cycles and were evaluable for response. Three patients (10%) achieved partial remission (PR) with a duration of 8-12 weeks; in 11 patients the disease was assessed as stable; and in 16 there was progression. A total of 40 patients were evaluable for toxicity. Nausea and vomiting occurred in 17 (43%), neuropathy, myopathy or myalgia in 8 (21%) and mucositis in 6 (14%). In addition to 3 patients taken off treatment before 4 treatment cycles, toxicity precluded further treatment in 3 others after 5, 6 and 7 cycles respectively. Methyl-GAG has minimal activity in renal cell cancer and, in this dose schedule, causes appreciable toxicity.
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PMID:An EORTC phase II study of methyl-glyoxal bis-guanylhydrazone in advanced renal cell cancer. 720 Aug 96