Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MITOMYCIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources
PubMedDate not supplied

The targeting of agmatine-liganded mitomycin C to an enzyme on the surface of tumour cells.

Tumour cells possess a cell surface protease referred to as guanidinobenzoatase (GB). We have synthesised a liganded form of mitomycin C which we refer to as MMC*. This MMC* has the fluorescent properties of mitomycin C and the additional ability to be directed to the active centre of GB by the agmatine moiety of the ligand. We have demonstrated the selective delivery of MMC* to the cell surface of tumour cells possessing active GB by fluorescent microscopy and competition experiments with molecules known to bind to the active centre of GB. The MMC* has a high affinity for tumour cell surface GB and we hope it may have potential in the selective delivery of mitomycin C in the chemotherapy of tumours in vivo.

Agmatine↗
PubMed1990

DNA interstrand cross-link and free radical formation in a human multidrug-resistant cell line from mitomycin C and its analogues.

A subline of the human breast tumor cell line (MCF-7), selected for resistance to Adriamycin and having the multidrug resistance phenotype, also developed significant cross-resistance to mitomycin C and its two analogues, BMY 25282 and BMY 25067. Because mitomycin C and the analogues contain both quinone and aziridine moieties, the mechanism of tumor cell kill is thought to involve alkylation and cross-linking of DNA molecules, hence they are not expected to show cross-resistance to cells selected for resistance to a DNA intercalator. Studies to understand this novel observation show that the resistant MCF-7 cells form significantly less hydroxyl radical and DNA cross-linking in the presence of mitomycin C and BMY 25282 than the sensitive cells. Although BMY 25067 formed less free radicals in the resistant cells, similar to the other two drugs, the formation of DNA cross-links was identical in both cell lines, indicating a somewhat different mechanism of tumor cell kill by this analogue. DNA cross-link formation increased slightly with time in the sensitive cells while there was a small decrease in the resistant cells. This difference in the formation of toxic intermediates appeared to result from enhanced detoxification of reactive species (hydrogen peroxide and alkylating intermediates) as a result of significantly higher glutathione peroxidase (14-fold) and glutathione S-transferase (44-fold) activities in the resistant cell line. These events, i.e., free radical formation and DNA alkylation, showed a good correlation with the cytotoxicity in drug-sensitive cells, indicating that both mechanisms contribute to cell killing of human breast tumor cells.

Alkylating Agents↗
PubMed1990

[Effect of mitomycin on the biosynthesis of extracellular endonuclease by Serratia marcescens].

The effect of mitomycin C on extracellular endonuclease activity of Serratia marcescens was studied. It was shown that in a concentration of 0.02-1.0 micrograms/ml, mitomycin C markedly increased biosynthesis of the endonuclease by growing and washed cells, the cell productivity being increased 80-100 times. The highest increase in the cell productivity was observed when mitomycin C was added to the cells at the end of the growth exponential phase. The increase in the activity of the extracellular endonuclease was due to the de novo synthesis of the enzyme since it was inhibited by chloramphenicol.

Chloramphenicol↗
PubMed1988

[A case report of long-term survival in advanced gastric cancer with multiple liver metastases treated with mitomycin C and tegafur therapy after palliative gastrectomy].

A 64-year-old male with advanced gastric cancer with multiple liver metastasis was treated with intensive chemotherapy including mitomycin C and tegafur after palliative gastrectomy. The patient was medicated with 30 mg iv of mitomycin C after surgery and 1,000 mg ir or 1,200 mg po of tegafur for one year for induction therapy and 400-600 mg po of tegafur for long-term maintenance therapy. All metastatic lesions in liver were completely eliminated three years after the start of treatment. As to acute and chronic toxicity, slight leukopenia was noted in the treatment, but the patient was found to show a good quality of life because of less toxicity. The patient has been healthy with no evidence of malignancy at nine years and nine months after the surgery. The total cumulative dose of tegafur in this treatment was 1,141.0 g, which is probably the largest dose ever reported in Japan, suggesting that the combination of mitomycin C and tegafur is indicated as a modality for advanced gastric cancer with liver metastasis.

Adenocarcinoma, Papillary↗
PubMed1989

Postoperative instillation of mitomycin C in the treatment of recurrent pterygium.

We examined retrospectively 61 eyes of 61 patients with recurrent pterygia who had been treated with excision, with or without 0.02% mitomycin C instillation, 3 to 7 years after treatment. The rates of recurrence (5% to 9%) and complications in eyes that had undergone excision and mitomycin C instillation were less than those in eyes that had had excision only. These data suggest that the postoperative instillation of 0.02% mitomycin C, twice a day for five days, may be effective and safe in the treatment of recurrent pterygium.

Conjunctival Diseases↗
PubMed1989

Precocious desynapsis of XY-bivalent in mouse germinal cells: influence of mitomycin C on tumour-bearing and normal mice.

A comparative study on the cytotoxic potential of anticancer-antibiotic mitomycin C has been made on tumour-bearing and normal mice considering precocious desynapsis of sex bivalent as parameter. The study indicates a strikingly differential effect of the drug on the phenomenon in two different types of mice. The administration of mitomycin C at therapeutic dose although enhances the frequency of precocious desynapsis of XY-bivalent in non-tumour (normal) mice to a significant extent (compared to control), the same drug at the same dose fails to produce a similar effect on tumour-bearing specimens. Discussions have been made on: (i) the probable cause for this differential effect, (ii) the mechanism of mitomycin action on precocious desynapsis of sex bivalent and, (iii) the possible significance of the findings in relation to cancer chemotherapy.

Animals↗
PubMed1989

Myeloprotective effect of diethyldithiocarbamate treatment following 1,3-bis(2-chloroethyl)-1-nitrosourea, adriamycin, or mitomycin C in mice.

The effect of diethyldithiocarbamate (DDTC) on myelotoxicity induced by 1,3-bis(2-chloroethyl)-1-nitrosourea, Adriamycin, or mitomycin C in C57BL/6J x DBA/2J mice is reported here. All drugs were administered i.v. Myelotoxicity was assessed, 24 h after administration of the myelotoxic drug, using bone marrow stem cell (spleen colony-forming unit) and granulocyte/macrophage progenitor cell (granulocyte/macrophage colony-forming unit in culture) clonogenic assays. Administration of DDTC alone had no effect on spleen colony-forming units or granulocyte/macrophage colony-forming units in culture. 1,3-Bis(2-chloroethyl)-1-nitrosourea showed a dose-dependent toxicity for both cell types, and subsequent treatment with DDTC (300 mg/kg i.v. 3 h after 1,3-bis(2-chloroethyl)-1-nitrosourea) ameliorated this toxicity. The same dosing regimen of DDTC ameliorated Adriamycin-induced toxicity to bone marrow stem cells at the two higher doses tested. However, the myelosuppressive effects of mitomycin C were not altered by DDTC administration (300 mg/kg i.v. 3 h after or 30 min before mitomycin C). These results demonstrate that DDTC ameliorates myelotoxicity induced by several, but not all, chemotherapeutic agents and suggest a broad role for DDTC in cancer chemotherapy.

Animals↗
PubMed1989

Antitumor activity of 7-N-(2-((2-(gamma-L-glutamylamino) ethyl) dithio) ethyl) mitomycin C (KW2149) against human tumor xenografts serially transplanted into nude mice.

The antitumor activity and toxicity of 7-N-(2-((2-(gamma-L-glutamylamino) ethyl) dithio) ethyl) mitomycin C (KW2149) were evaluated using a human tumor xenograft--nude mouse system, and compared with those of the maternal compound, mitomycin C. The maximum tolerated dose of KW2149 was estimated to be 15 mg/kg by bolus intraperitoneal or intravenous injection, at which a remarkable reduction of spleen weight was observed, suggesting bone marrow suppression by this agent. A bolus injection of KW2149 seemed to be more effective than a divided injection schedule, when a total of 15 mg KW2149/kg was administered to mice bearing breast (MX-1) and colon (Co-4) carcinomas. The antitumor activity of KW2149 was dose-dependent, and the difference in antitumor effect according to route of administration was minimal. The antitumor spectrum of KW2149 was essentially identical to that of mitomycin C administered intraperiotoneally as a bolus at a dose of 6 mg/kg.

Adenocarcinoma↗
PubMedDate not supplied

Decomposition of mitomycin and anthracycline cytostatics in cell culture media.

The chemical stability of members of two groups of cytostatics, mitomycins and anthracyclines, has been studied in four different cell culture media enriched with serum. Stability was determined with the use of high performance liquid chromatography. In the group of mitomycins, the 7-aminomitosanes appeared to be relatively stable during a seven days incubation period at 37 degrees C when compared to the 7-methoxy congeners. The anthracycline derivatives, 4-demethoxy-daunorubicin, doxorubicin and its 4'-analogues showed half-lives of about 10-20 hours. Doxorubicinol and daunorubicin were found to be more stable. Anthracycline degradation products could be traced with the use of thin layer chromatography. All main degradation products originate from hydrolytic reactions. No enzymatic conversions could be observed. These observations may be of importance for the correct interpretation of the effects of mitomycins or anthracyclines on cells incubated in a cell culture medium.

Antibiotics, Antineoplastic↗
PubMed1986

Fumaric acid enhances DNA synthesis of rat hepatocytes by counteracting the toxicities of mitomycin C and aflatoxin B1.

The effect of fumaric acid was examined on DNA synthesis in hepatocytes or hepatoma cells from rats treated with toxic agents. Male Donryu rats were injected with mitomycin C or aflatoxin B1, singly or in combination with fumaric acid. After a specified period, hepatocytes were isolated from the liver by the collagenase perfusion method and placed in culture, and their activities for DNA synthesis were measured. The iv injection of rats with mitomycin C (0.5 mg/kg) reduced the semiconservative DNA synthesis of the hepatocytes, but simultaneous dosing of fumaric acid (40 mg/kg) enhanced the recovery of the DNA synthesis. The DNA synthesis of hepatoma cells, a 3'-methyl-4-(dimethylamino)azobenzene-induced transplantable cell line growing in the abdominal ascites of rats, was also reduced by the iv injection of mitomycin C but, in contrast to that of the hepatocytes, was little influenced by the simultaneous dosing of fumaric acid. The ip injection of fumaric acid also reduced the toxicity of aflatoxin B1 (0.25 mg/kg, ip), preventing the reduction of DNA synthesis as well as the occurrence of nuclear degenerative changes in the aflatoxin B1-exposed hepatocytes.

Aflatoxin B1↗
PubMedDate not supplied

Toxicity and pathological effects of a new dosage form of mitomycin C for carcinomatous peritonitis.

A new dosage form (MMC-CH) of mitomycin C (in a suspension of activated carbon adsorbing mitomycin C in saline), designed for intracavitary use in carcinomatous peritonitis, was studied for its toxicity and pathological effects in rats. The LD50 values determined with the Litchfield-Wilcoxon's method in three types of MMC-CH were 7.6 (100 micrograms/ml MMC and 0.5 mg/ml activated carbon in saline), 16.5 (100 micrograms/ml MMC and 0.75 mg/ml activated carbon in saline), and more than 25 mg/kg (100 micrograms/ml MMC and 1 mg/ml activated carbon in saline), while in mitomycin C solution the value was 3.05 mg/kg. The lethal toxicity decreased with the change of dosage form. Studies on survival, symptoms of intoxication and macroscopic and microscopic examinations of autopsied animals revealed that there was no evidence of any additional side effects produced by the change of dosage form.

Animals↗
PubMed1987

Effect of mitomycin-C and cyclophosphamide on the polytene chromosomes of Anopheles stephensi (Culicidae:Diptera).

Polytene chromosomes from the salivary glands of the mosquito, Anopheles stephensi, were used to evaluate the mutagenic effect of mitomycin-C and cyclophosphamide. Second instar larvae were treated with 1.4 micrograms/ml of mitomycin-C and 20.7 micrograms/ml of cyclophosphamide separately for 24 h. Polytene chromosome preparations were made from the salivary glands of 4th instar larvae. Mitomycin-C treated stocks showed as many as 46.99 +/- 2.48% aberrations compared with 7.5 +/- 0.80% in the controls. Similarly, cyclophosphamide treated larvae showed the aberrated cells to be 36.65 +/- 1.45% as against 7.93 +/- 0.52% in the controls. The results were statistically significant (P less than 0.001) for the two antitumour drugs. Both drugs are mutagenic to polytene chromosomes which are sensitive indicators of DNA damage.

Animals↗
PubMed1987

Effect of mitomycin C on specific gene transcript levels in cultured mammalian cells.

The effect of mitomycin C on the accumulation of specific mRNAs was studied in asynchronously growing Swiss 3T3 cells, as well as in synchronously growing serum stimulated ts13 cells (a temperature-sensitive mutant from the BHK cell line). It was observed that the steady-state level of p53 RNA experienced some increase in 3T3 cells treated for 24 h with the drug. In addition, mitomycin when applied to serum stimulated ts13 cells increased the level of p2F1 RNA. Mitomycin diminished the level of core histone H3 RNA, a finding consistent with the inhibitory action of this compound on DNA replication.

Animals↗
PubMed1988

Phase II trial of mitomycin C plus 5-FU in the treatment of drug-refractory ovarian cancer.

Following cisplatin combination chemotherapy for advanced epithelial type ovarian cancer, response to subsequent treatments has proved relatively poor. Mitomycin C and 5-fluorouracil (5-FU) have both been reported to have useful activity as single agents in patients with drug-refractory ovarian cancer. We have carried out a phase II trial of a combination of these two agents in 25 patients who had previously received a median of two chemotherapy regimens (range, one to five regimens). Patients received mitomycin C, 10 mg/m2 intravenously (IV) on day 1 every 6 weeks, and 5-FU, 500 mg/m2 IV daily on days 1 to 3 every 3 weeks. Four patients experienced a complete response and six patients a partial response, for an overall objective response rate of 40%. The median duration of complete and partial responses was 8 and 4 months, respectively. The median duration of survival for all 25 patients was 10.5 months (range, 2.5 to 49+ months). The most prevalent toxicity was bone marrow suppression. Leukopenia occurred in 68% of the patients, and 36% experienced thrombocytopenia. Severe or life-threatening bone marrow suppression was observed in 36% of the patients and required dose reduction or drug discontinuance in 28% and 24%, respectively. We conclude that mitomycin C plus 5-FU combination therapy appears to be extremely active in patients with drug-refractory disease. Confirmatory trials are indicated.

Adult↗
PubMed1988

[Mitomycin C induced structural changes in heterochromatic regions of human chromosomes 1, 9, 16 and Y].

Aberrations and variations in the heterochromatic blocks of chromosomes 1, 9, 16 and Y were found under the influence of mitomycin C in cultured lymphocytes of peripheral human blood. Lymphocytes were cultured during 96 hours, mitomycin C in final concentration of 0.3 mkg/ml was present in the culture during the latest 24 hours of culturing. Different changes in the heterochromatic regions of chromosomes were found in approximately 30% of cells: in 6.3% of cells mitotic chiasmata were indicated. In 9.5% of cells isolocus breaks were observed in heterochromatic region of chromosome 1 in segment 1q11. In the latter case this may be a fragile site detected under the influence of mitomycin C on the lymphocytes.

Cells, Cultured↗
PubMed1986

Trial of the combination of mitomycin, vindesine, and cisplatin in patients with advanced non-small cell lung cancer.

In prior trials, mitomycin, vindesine, and cisplatin have each been shown to have reproducible antitumor activity as single agents when used in the treatment of patients with non-small cell lung cancer. The two-drug combinations of vindesine plus high-dose cisplatin or mitomycin have shown an improved major response rate and manageable toxicity in prior trials. In this report, 90 patients with stage III non-small cell lung cancer were treated with the three-drug combination of mitomycin (8 mg/m2), vindesine (3 mg/m2), and high-dose cisplatin (120 mg/m2). Eighty-seven patients (97%) were adequate for both response and toxicity. Major objective responses occurred in 60% of the patients. The toxicity of this regimen was predictable and manageable when established supportive care measures were employed. Based on the response rate observed, the combination of these three agents merits further study in randomized trials against other chemotherapeutic regimens and consideration of its use in adjuvant and preoperative settings.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

[Nephrotoxicity of mitomycin C (apropos of 25 case reports). Results of a multicenter survey organized by the Society of Nephrology].

We have studied 25 cases of hemolytic and uremic syndrome (H.U.S.) induced by mitomycin C, collected from 1976 to 1982 in 12 Nephrology Centers. Mitomycin C was administered in successive cures at a cumulative dose higher than 50 mg/m2. This H.U.S. is characterized by its slow and late occurrence, by extra-renal, mainly respiratory, manifestations that may reveal the disease, and finally by its pathological aspects. Mesangiolysis and endothelial or mesangial enlarged and atypical nuclei are observed in addition to the usual lesions of thrombotic micro-angiopathy. The prognosis was very poor in the first cases reported. It was better, however, in the patients studied more recently, because the cumulative dose was lower. In severe cases, plasma exchange might improve long-term prognosis. The disease might be due to a direct toxic effect of mitomycin C on the vascular endothelium.

Adult↗
PubMed1985

Pulmonary angiomatoid vascular changes in mitomycin C-associated hemolytic-uremic syndrome.

Angiomatoid vascular changes in lungs and pulmonary hemorrhage are described in a woman in whom mitomycin C-associated hemolytic-uremiclike syndrome developed. These changes represent part of the spectrum of vascular damage that may complicate mitomycin therapy. Patients receiving mitomycin C chemotherapy require careful monitoring for possible development of these complications.

Female↗