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

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 Lewis lung carcinoma, implanted in the footpad of BDF1 mice, was used for testing a preoperative chemotherapeutic treatment in comparison to a postoperative one, or to surgery alone. We administered both drugs effective in this model (Cyclophosphamide, Ifosfamide, CCNU), as well as ineffective ones (Ftorafur, Methyl-GAG, Vincristine) in order to study all the possible influences on the treatment outcome. In nine different experiments one active and one inactive drug were always compared in various schedules. Groups with surgery alone at an early or later stage were used as controls. The results showed that preoperative adjuvant treatment with an active drug decisively improved the survival time and the number of cured animals compared to surgery alone. The administration of an inactive drug and postponement of surgery decreased the number of cures, while the lifespan of the animals dying from lung metastases was not influenced. An improved treatment outcome compared to surgery alone resulted in cases where the preoperative inactive treatment was replaced by postoperative treatment with an active drug-a procedure also common and applicable for clinical practice. The body weight of the animals, noted as a sign of toxicity, was lowered when a cytostatic drug was used in addition to removal of the primary tumor. There was no difference between pre- or postoperative and repeated administrations. Based on these results preoperative adjuvant cytostatic treatment with histological control of response and decision for postoperative adjuvant treatment is recommended for clinical practice.
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PMID:Preoperative (neoadjuvant) chemotherapy in the murine Lewis lung carcinoma and possible implications for clinical use. 359 36

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

The effect of Methyl-GAG on a transplantable murine renal cell adenocarcinoma was evaluated. Inoculation of Balb/C mice with 1 X 10(5) renal adenocarcinoma cells under the renal capsule resulted in 100% tumor growth and death of the animal in 29 +/- 5 days. In 66% of the control animals lung metastases was observed. Intraperitoneal injections of Methyl-GAG at dose levels of 200 mg/m2, 150 mg/m2, and 100 mg/m2 administered weekly failed to demonstrate any effect on local growth of the tumor. More than 50% incidence of metastatic development was noted in the treated groups. Methyl-GAG had no apparent effect on primary tumor growth or the retardation of metastatic incidence.
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PMID:The effects of Methyl-GAG on a transplantable murine renal cell adenocarcinoma. 684 33