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PubMed1980

Specific tumor immunity induced with mitomycin C-treated syngeneic tumor cells (MCT). Effects of carrageenan and trypan blue on MCT-induced immunity in mice.

Mitomycin C treatment of 3-methylcholanthrene-induced syngeneic tumor cells in male mice of the highly inbred strain CBA/WEHI was a convenient and effective method for producing viable but nondividing tumor cells. A single sc injection of 1 x 10(6) mitomycin C-treated syngeneic tumor cells (MCT) induced a specific antitumor immune response that could mediate rejection of small subcutaneous tumor grafts and substantially inhibit growth of larger grafts in normal mice. The response was evident between 3 and 7 days after immunization and persisted for at least 120 days. Adoptive transfer experiments with peritoneal exudate cells from MCT-immunized mice indicated that a cellular basis for resistance was likely in the absence of a detectable humoral component. Administration of MCT to mice with established tumor grafts did not, however, affect tumor growth. Experiments with carrageenan and trypan blue showed that neither induction nor expression of cytotoxic effector cells in MCT-immunized mice was inhibited by these substances, though carrageenan and trypan blue augmented tumor growth in normal mice.

Animals↗
PubMed1980

Action of mitomycin C on testicular steroidogenesis in immature rats.

Treatment with mitomycin C resulted in a decrease in the testicular delta 5-3 beta-hydroxysteroid dehydrogenase level along with a fall of Leydig cell nuclear area. Following the same treatment the significant fall of sex accessory organ weights and testicular accumulation of ascorbic acid and cholesterol were noted. On the basis of above evidence it is suggested that mitomycin C probably suppressed testicular steroidogenesis.

3-Hydroxysteroid Dehydrogenases↗
PubMed1978

[Repair of damage to cells in an SPEV culture after exposure to mitomycin C].

The action of mitomycin C on a porcine embryo kidney culture (in dose of 0.5-1.5 mkg/ml in the course of 24-72 hours) is accompanied by significant changes in the ultrastructure and morphology of cells. Moreover, mitomycin C sharply inhibits DNA synthesis, mitotic activity and much more weakly suppresses protein and RNA syntheses. After a prolonged (48 hours) washing of the antibiotics only the mitochondrial ultrastructure is restored in the fresh cultural medium. DNA synthesis and mitotic activity remain suppressed, while protein and RNA syntheses increase sharply, which leads to protein accumulation in cells, and to the enlargement of nuclei, nucleoli and cells. Such changed cells are unable to keep on living and perish.

Cell Line↗
PubMed1982

Doxorubicin, mitomycin, and 5-FU (DMF) in the treatment of hormone-resistant stage D prostate cancer: a preliminary report.

Fifteen patients with advanced stage D hormone-resistant prostate cancer were treated with the combination of doxorubicin, mitomycin, and 5-FU. Nine patients (60%) had objective responses, with a mean duration of 27.9 weeks. No responding patient had relapsed. Although three patients developed a culture-negative leukopenic fever, no deaths from chemotherapy occurred. Preliminary results with doxorubicin, mitomycin, and 5-FU indicate that this is a very effective chemotherapy regimen, resulting in a high objective response rate in metastatic prostate cancer.

Adenocarcinoma↗
PubMed1982

Phase I--II study of the combination of 5-FU, doxorubicin, mitomycin, and semustine (FAMMe) in the treatment of adenocarcinoma of the stomach, gastroesophageal junction, and pancreas.

One hundred and fifteen patients with advanced gastrointestinal cancer (stomach cancer, 42 patients; gastroesophageal junction cancer, ten; pancreatic cancer, 32; and other upper gastrointestinal cancers, 31) were treated with a combination chemotherapy regimen consisting of 5-FU, doxorubicin, mitomycin, and semustine (methyl-CCNU) (FAMMe). Of the 31 patients with stomach cancer who were evaluable for response and had had no previous chemotherapy, 12 (39%) achieved complete or partial remission. One of eight (12%0 patients with gastroesophageal junction cancer and five of 23 (22%) patients with pancreatic cancer achieved a partial remission. The median duration of survival for all patients with adenocarcinoma of the stomach was 7.1 months. The median duration of survival for responding patients with stomach cancer was 13.6 months, and the median survival for nonresponding patients was 6.1 months. FAMMe chemotherapy was generally well-tolerated and can be administered in adequate doses without producing prohibitive myelosuppression. The starting dose should be reduced for patients greater than or equal to 70 years old or for patients who have received pelvic or vertebral radiation therapy. FAMMe is effective against advanced gastric cancer; however, because this was not a randomized comparative study of the relative effectiveness of FAMMe and FAM (5-FU, doxorubicin, and mitomycin), no recommendation for the use of one regimen instead of the other for advanced adenocarcinoma of the stomach can be made. FAMMe chemotherapy cannot recommended for advanced adenocarcinoma of the pancreas and gastroesophageal junction.

Adenocarcinoma↗
PubMed1982

Mitomycin C: phase I study of a constant infusion ambulatory treatment schedule.

Thirty patients received mitomycin C by constant infusion for 5 consecutive days (16 patients ) or for extended period by an ambulatory infusion pump (Cor-Med model) for 9 to 30 days (14 patients). The short-term 5-day infusions were delivered at dose rates of 2, 3, 4, 5 and 6 mg/m2/d with a cumulative dose of 15-50 mg. The protracted infusions were delivered at dose rates of 0.75-3 mg/m2/d with a cumulative dose of 21.6-65.2 mg. Marrow suppression was dose-limiting and occurred in 5/6 evaluable patients receiving more than 30 mg in the short-term infusion schedule and 8/10 evaluable patients receiving more than 20 mg in the protracted infusion schedule. The characteristics of the marrow suppression are that: a) thrombocytopenia precedes or is observed without concomitant leukopenia and b) the nadir day is delayed (WBC day 42, platelet day 36). Mitomycin C delivered by constant infusion leads to dose-limiting marrow toxicity at 20 to 30 mg cumulative dose depending upon the dose rate and duration of treatment. For short-term 5-day therapy, 3 mg/m2/d and for protracted therapy (up to 30 d) 0.75 mg/m2/d are the recommended dose rates for the constant infusion schedule.

Adult↗
PubMed1980

In vitro thermochemotherapy of human colon cancer cells with cis-dichlorodiammineplatinum(II) and mitomycin C.

The thermosensitivity of human colon adenocarcinoma (LoVo) cells was investigated as a function of temperature and duration of heating in exponentially growing cultures. At 39-43 degrees, time-dependent survival followed a simple exponential function. Do values decreased progressively with a rise in temperature, from Do at 40 degrees = 38 hr to Do at 42 degrees = 17 hr to Do at 43 degrees = 1.5 hr. thus indicating relative thermoresistance of LoVo cells compared to Chinese hamster ovary cells. Dose-dependent 1-hr survival of LoVo cells treated with cis-dichlorodiammineplatinum(II) and mitomycin C was effectively modified when treatment was conducted under hyperthermic conditions. For both agents and cultures in exponential and stationary growth phases, hyperthermia abolished the initial shoulder portion and steepened the subsequent exponential part of the survival curves for dose-modifying factors at the 10% survival level of 1.5 to 2.0 at 41 degrees and 2.6 to 2.8 at 42 degrees. This significant enhancement of drug-induced cell kill by moderate hyperthermia suggests that thermochemotherapy with mitomycin C and cis-dichlorodiammineplatinum(II) should be tested clinically with both regional and total-body hyperthermia.

Adenocarcinoma↗
PubMed1980

Morphological effects of mitomycin C administered intravesically to normal mice and mice with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induce bladder neoplasms.

The intravesical administration of mitomycin C to normal and N-[4-(5-nitro-2-furyl)-2-thiozolyl]formamide-induced bladder tumor-carrying mice at initial concentrations of 2 and 5 mg/ml for 2 hr resulted in marked morphological effects including cytoplasmic and nuclear abnormalities and disruption of surface architecture. Tumors cells and normal urothelial cells were sensitive to the effects of mitomycin C. These effects were limited to epithelial cells.

Animals↗
PubMedDate not supplied

Phase I-II study of mitomycin C topical therapy for low-grade, low stage transitional cell carcinoma of the bladder: an interim report.

Intravesical mitomycin C therapy was administered to 63 patients with noninvasive bladder carcinoma in a phase I-II study. Doses ranged from 20 to 60 mg once a week for 8 weeks. The overall response rate was 67% including a complete remission rate of 45%. The median duration of complete remission for the two lowest dose groups was > 14 months, with a range of 1-36+ months. Followup is not yet adequate to determine the median duration of complete remission for the higher dose groups. No bone marrow suppression or other systemic toxic effects were noted. Adverse effects were localized and occurred infrequently. No mitomycin C was detected in serial serum samples after intravesical instillation.

Absorption↗
PubMed1980

[Fluorouracil, mitomycin-C and adriamycin in the treatment of metastasizing gastrointestinal adenocarcinomas].

28 patients with advanced adenocarcinomas were treated with combinations of 5-fluorouracil and mitomycin-C (FM, 21 patients) or of 5-fluorouracil, adriamycin and mitomycin-C (FAM, 7 patients). 5 patients responded, 3 showing an objective response of more than 50% lasting 3-5 months. Toxicity was primarily hematologic, chiefly comprising severe thrombopenias. The results indicate that with these combinations a limited palliative effect can be achieved in only a few patients.

Adenocarcinoma↗
PubMed1994

Mitomycin C: a prototype bioreductive agent.

Hypoxic cells of solid tumors represent a therapeutically resistant population that limits the curability of many solid tumors by x-irradiation and by most chemotherapeutic agents. The oxygen deficit, however, creates an environment conducive to reductive processes that results in a major exploitable difference between normal and neoplastic tissues. Mitomycin C (MC) can be reductively activated by a number of oxidoreductases, in a process required for the production of its therapeutic effects. This enzymatic reduction results in preferential activation of MC under hypoxia and, in most instances, the production of greater toxicity to oxygen-deficient cells than to their oxygenated counterparts. DNA appears to be the most important target of the reactive species generated from MC, with both mono- and bis-adducts of DNA being formed in drug-treated cells. The demonstration that MC, used to kill the hypoxic fraction, in combination with x-irradiation, to eradicate the oxygenated portion of the tumor, produced enhanced cytodestructive effects on solid tumors of animals has led to the clinical evaluation of the mitomycin antibiotics in combination with x-rays in patients with cancers of the head and neck. The findings from these clinical trials have demonstrated the utility of directing a concerted therapeutic attack on the hypoxic fraction of solid tumors as an approach toward enhancing the curability of localized neoplasms by x-irradiation.

Animals↗
PubMed1995

[An experimental investigation on preventive measures of skin ulcers induced by extravascular mitomycin C].

In order to make an investigation on skin ulcer induced by Mitomycin C extravasation, the preventive measures were undergone by the following ex-periment. A subcutaneous ulcerative model induced by 0.1mg Mitomycin C (MMC) extravasation in the leg of BALA/C mice was established. On the model subject, 8 pharmacologic adjuvants or physical modulation were adopted. It is preferential to choose local injection with 0.1 ml 99% dimethyl sulfoxide (DMSO), or with additional smearing DMSO on the affected skin. 10 days later, the ulcerative areas with DMSO treatment were significantly decreased in contrast with 0.1 ml 0.9% NaCI treatment (P < 0.001). The other preferential treatment were in turn by the injection of 0.1 ml 5% NaHCO3 (P < 0.001); 0.1 ml 1% procainamidi hydrochloridum (including 0.4% dexame-thasonum) (P < 0.001) or smearing with 0.1 ml 90% DMSO (including 10% Vit E) (P < 0.01). Delayed application of DMSO after MMC extravasation 30 min had been proven the limited effects on the prevention of ulcer (P < 0.05). Neither cooling of skin or local injection of sodium thiosulfate reduced MMC ulceration (P > 0.05). The mechanisms of prevention of MMC extravascular ulcer by DMSO or 5% NaHCO3 were briefly discussed.

Animals↗
PubMed1993

[Combination of cisplatin-mitomycin-vindesine for inoperable, non-small-cell bronchial cancers. French study group in pneumo-cancerology].

The efficacy of the association of cisplatinum-mitomycine and vindesine on inoperable non-small cell bronchial cancer has been assessed in a prospective study. Cisplatinum 120 mg/m2 and mitomycine 8 mg/m2 on day 1, day 28 and day 70, and vindesine 3 mg/m2 once per week for the first cycle, once every 15 days for the second and third cycles. 98 patients were included in the study between February 1989 and June 1990: there were 89 men and 9 women with a mean age of 60. There were 57 epidermoid cancers, 22 adenocarcinomas, 1 neuroendocrine carcinoma and 18 large cell cancers. There was an objective response (RO) in 25% (of whom 5% had a complete response) without any significant difference between the 56 cancers at stage III (32% RO) and 42 cancers in stage IV (17% RO). The median survival of the responders was 14 months again 5 months for the non-responders. The initial loss of weight seemed to be a prognostic factor because the number of objective responders was significantly greater in the patients with only a small weight loss: 37% of RO if the weight loss was less than 5%, against 11% for a weight loss of greater than 5%. The myelotoxicity of this association was important because 85% of those patients presented with a leucopenia at least grade II OMS. Peripheral neuropathies occurred in 27% of cases: 4 cases of cardiotoxicity were reported.

Actuarial Analysis↗
PubMedDate not supplied

[Intraoperative support of trabeculectomy with mitomycin].

The authors evaluated the efficacy of pharmacological support of trabeculectomy by intraoperative application of mitomycin. It was used in selected cases, those of high risk glaucoma as regards to poor surgical effect, in concentrations 0.2 mg/ml and 0.5 mg/ml. There were 32 eyes with following types of secondary glaucoma: neovascular glaucoma in diabetes, glaucoma in aphakic and pseudophakic eyes and simple glaucoma in the eyes after uneffective trabeculectomy. Normalization of the intraocular pressure was achieved in 21 eyes (65.6%). The 1.5-year follow-up revealed that with higher concentrations of mitomycin normalization of the pressure was more frequent lait there occurred more complications than with lower concentrations. Long-lasting hypotony is a difficult complication.

Adult↗
PubMedDate not supplied

Tenon's cyst formation after trabeculectomy with mitomycin C.

One hundred eyes of 100 patients in whom Tenon's cysts (TCs) developed in the early postoperative period following trabeculectomy with mitomycin C were retrospectively studied to determine their incidence, possible risk factors associated with their development, and the clinical course of the patients in whom they occurred. The incidence of TC formation was 29/100 (29%). Significantly more cysts developed in the men than in the women. There were no significant differences between those patients in whom TCs developed and those in whom they did not in terms of age, race, type of preoperative medications, mean preoperative intraocular pressure (IOP), prior argon laser trabeculoplasty, prior trabeculectomy, prior Tenon's cyst formation, or prior cataract surgery. The 29 patients in whom a Tenon's cyst developed had a mean follow up of 22.0 +/- 12.9 weeks, with a mean IOP at the last examination of 14.2 +/- 6.3 mm Hg (as compared with 20.7 +/- 8.3 mm Hg at the time of diagnosis). One patient required a repeat trabeculectomy with mitomycin C. Two patients required bleb needling, subsequent TC excision, and eventual seton placement. Of the remaining 26, 14 (54%) required no glaucoma medication for IOP control, 11 (42%) required one, and 1 (4%) required two.

Combined Modality Therapy↗
PubMed1994

[Targeting treatment of human HCC xenografts implanted in nude mice using bifunctional antibody HC-1 combined with mitomycin C].

Bifunctional antibody (BFA) HC-1 possessing one binding site for mitomycin C (MMC) and a companion site directed against human hepatocellular carcinoma (HCC) cell membrane was constructed by chemical conjugation of two Fab' fragments of McAb MMC-1 and McAb HCMP-1. BFA could be specifically attached to tumor xenograft of nude mice bearing human HCC and thus simultaneously capture mitomycin C. The attachment of these complexes was detected by radioimmunoimaging in nude mice bearing human HCC using 131-I labelled BFA HC-1. Clear imaging of the tumor was obtained in 6 days after i.p. injection. On the 8th day after the injection, tumor/liver (T/L) ratio was 8.04 +/- 0.45. When the BFA HC-1 was used to be combined with MMC for the targeting treatment of human HCC implanted in nude mice, the highly significant suppression of tumor growth was achieved. After two months of treatment, xenografts of 40% (4/10) mice disappeared and 60% (6/10) of the mice survived. Those mice treated only with MMC became more and more sick even if the grafted tumors shrank, and all of them died within 2 months after therapy. The controls were treated with nonspecific IgG. Tumors grew very fast, and most of the controls died in 1 month after the first injection. The results suggest that BFA HC-1 could concentrate MMC on the human HCC cells, and it is a kind of suitable carrier for the targeting treatment of human HCC.

Animals↗
PubMed1994

Constrictive pericarditis after sclerosing therapy with mitomycin C for malignant pericardial effusion: report of a case.

Malignant pericardial effusion with cardiac tamponade is a life-threatening oncological emergency. Pericardiocentesis with sclerosing therapy is a life-saving palliative treatment procedure. Because of the short life expectancy in these patients, pericardial constriction after pericardial sclerosing therapy has been rarely reported in the literature. We report a patient with malignant pericardial effusion and cardiac tamponade which was successfully controlled by intrapericardial mitomycin C instillation. This patient developed pericardial constriction six months after mitomycin C pericardial sclerosis. It should be noted that pericardial constriction may occur if a patient survives long enough after successful pericardial sclerosis.

Cardiac Tamponade↗
PubMed1994

[The prevention of peritoneal dissemination of gastric cancer with intraperitoneal activated carbon particles absorbing mitomycin C].

A new drug dosage form comprising activated carbon particles absorbing mitomycin C (MMC-CH) has the advantage of being retained in the peritoneal cavity and distributes a larger amount of mitomycin C for a long time. Some 113 patients with gastric cancer and serosal infiltration were randomly assigned intraperitoneal treatment with MMC-CH and no anti-cancer drugs. There were significant differences in survival rate between the patients who have no visible peritoneal dissemination with MMC-CH and without. Thus, intraoperative intraperitoneal treatment with MMC-CH improves survival after gastrectomy for gastric cancer and seems effective against peritoneal recurrence.

Absorption↗