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[The inhibitory effect of mitomycin C applied by intracapsular method on rabbit lens epithelial cells: an experimental study of after-cataract].

OBJECTIVE: To study the inhibitory effect of Mitomycin C applied by intracapsular infusion method on rabbit lens epithelial cells and its intraocular toxicity. METHODS: 0.2 ml Mitomycin C with different concentration (0.1 mg/ml, 0.2 mg/ml, 0.4 mg/ml) was injected into the capsular bags of the rabbits' lens during the hydrodissection of phacoemulsification. The drug was exposed to the lens epithelial cells directly and transiently. In the two-month follow-up after the operation, the posterior capsule opacification and the change of intraocular pressure were observed and compared between the control group and the experimental group; the histopathologic and the ultrastructural changes were also observed. RESULTS: For clinical study in the rabbit, the posterior capsule opacification only appeared in the control group two weeks after the operation. Four weeks after the operation, the posterior capsular opacification in the eyes of experimental group was not so obvious as that of the control group. The higher the concentration of the drugs, the less the posterior capsule opacification was shown. There was no obvious difference in the postoperative inflammation between the control group and the low, middle-concentration experimental group. Slight toxic reaction was shown on the rabbits' eyes of the high-concentration experimental group in the early stage after the operation. The histopathologic examination showed that the proliferation of lens epithelial cells in the control group was more obvious than that in the experimental group. Mitomycin C could cause the degeneration of lens epithelial cells. The degree of degeneration was related to the drug's concentration. The ciliary bodies of the rabbits' eyes in the high-concentration experimental group were infiltrated by inflammatory cells and bled slightly. CONCLUSION: Mitomycin C can inhibit the proliferation of lens epithelial cells effectively. Its intensity is related to the drug's concentration. It's a safe and effective drug in the prevention of after-cataract when the concentration of 0.1-0.2 mg/ml was applied in the capsular bag.

Animals↗

Needle revision of failed filtering blebs augmented with subconjunctival injection of mitomycin C.

OBJECTIVE: To evaluate the short-term efficacy and safety of needle revision of failed filtering blebs augmented with subconjunctival injection of mitomycin C. PATIENTS AND METHODS: Needle revision of failed filtering blebs followed by subconjunctival injection of 10 to 20 microg of mitomycin C was performed in 41 eyes. Short-term results were analyzed 6 months postoperatively. RESULTS: The mean (+/- standard deviation [SD]) intraocular pressure decreased from 26.4 +/- 6.2 to 16.4 +/- 6.5 mm Hg (P < .001), and the mean (+/- SD) number of medications decreased from 2.8 +/- 1.4 to 0.7 +/- 1.1 (P < .001). The overall success rate (defined as intraocular pressure between 5 and 21 mm Hg and no serious complications) was 76%. Initial intraocular pressure, number of previous surgical procedures, type of glaucoma, and lens status did not influence the success rate. The resulting bleb was significantly larger in the successful cases (2 +/- 0.8 vs 0.33 +/- 0.5; P < .001). Complications included one case of late suprachoroidal hemorrhage. The mean (+/- SD) visual acuity remained stable (delta visual acuity in Snellen lines = 0.023 +/- 1.1). CONCLUSION: Needle revision followed by subconjunctival injection of mitomycin C is an alternative to more complicated surgical procedures in cases of failed filtering blebs. Bleb formation was essential for successful reduction of intraocular pressure, which suggests subconjunctival injection of mitomycin C by itself may not lower intraocular pressure.

Adolescent↗

Enhancement of xanthine dehydrogenase mediated mitomycin C metabolism by dicumarol.

These studies examined the effect of dicumarol on xanthine dehydrogenase (XDH), an enzyme recently shown to bioreduce mitomycin C. Dicumarol, which has previously been shown to inhibit xanthine oxidase (XO), inhibited both XDH and XO mediated conversion of xanthine to uric acid but potentiated the metabolism of mitomycin C by XDH and XO. Formation of 2,7-diaminomitosene following mitomycin C bioactivation by XDH was increased 3-fold aerobically and 4-fold hypoxically when 20 microM dicumarol was included in the reaction mixture. XO mediated metabolism of mitomycin C hypoxically was increased approximately 50% by the inclusion of dicumarol.

Animals↗

[Mitoxantrone (MTX) versus mitomycin C (MMC) in the ablative treatment of Ta, T1 superficial bladder tumors. Phase III, randomized prospective study].

A prospective randomized study was conducted to determine the ablation capacity of mitoxantrone in Ta-T1 superficial bladder tumors versus mitomycin C, a drug whose intravesical ablation properties are well-known. Fifty-seven patients comprised the study. The tumor was not completely resected when the patient underwent TUR. This residual tumor was used as control. The patients were treated with either 20 mg Mitoxantrone or 40 mg mitomycin C weekly for 8 weeks and two other instillations every 15 days in 50 ml saline solution. Response to therapy was evaluated between the 4th and 8th week and classified as complete response (CR), defined as no gross and microscopic evidence of residual tumor, or no response (NR) or therapeutic failure. CR was observed in 77.7% of the patients treated with mitomycin C and in 50% in those that had been treated with Mitoxantrone. Treatment was discontinued because of side effects in 15% of the patients treated with mitomycin C and in 63.4% of those who received Mitoxantrone. We can conclude from the results of the present study that Mitoxantrone is a useful agent for ablation therapy of superficial bladder tumors, although the high incidence of severe side effects warrants its limited use and at high dilutions.

Female↗

[An experimental study on high intensity focused ultrasound combined with mitomycin treatment of bladder tumor].

OBJECTIVE: To study the therapeutic effect and synergistic inhibition effect of high intensity focused ultrasound in combination with mitomycin on T739 mice bladder tumor. METHODS: BTT739 tumor-bearing mice receiving HIFU and/or mitomycin in two weeks, were divided into control group, low dose chemotherapy group, high dose chemotherapy group, HIFU group and HIFU combined chemotherapy group. The growth of mice tumor volume was observed in two weeks, by which we counted tumor volume doubling time and performed the growth curve. All specimens were analysed histologically. RESULTS: HIFU combined mitomycin has significant synergistic inhibition effect. Tumor tissue damage such as huge coagulation necrosis was observed using light microscopy. However, there were still some remaining alive cells. The apoptosis of tumor cell in HIFU group and HIFU combined chemotherapy group obviously increased in comparison with other groups. CONCLUSIONS: HIFU group, HIFU combined chemotherapy group can distinctively inhibit tumor growth; HIFU combined with mitomycin has notable synergistic inhibitory effect. HIFU may induce the apoptosis of tumor cell.

Animals↗

The role of circulating immune complexes and biocompatibility of staphylococcal protein A immunoadsorption in mitomycin C-induced hemolytic uremic syndrome.

Mitomycin-induced hemolytic uremic syndrome (HUS) is a life-threatening complication of this therapy, and increased levels of circulating immune complexes and hypocomplementemia have been found in some patients. We further characterize the role of immune complexes in mitomycin-HUS by showing that removal of these complexes by immunoadsorption with staphylococcal protein A columns correlates with temporal improvement in the microangiopathic hemolytic anemia in this disorder. Two immune complexes bound to the protein A column were identified: an 11S platelet-aggregating protein and a 15S non-platelet-aggregating protein. In addition, the patient had anaphylactoid reactions at the onset of immunoadsorption similar to first-use dialysis reactions that correlated with increases in complement 3a and 5a, interleukin-1 (IL-1), IL-6, and tumor necrosis factor levels. This case suggests that platelet-aggregating and complement-fixing circulating immune complexes are, in part, a proximate cause for mitomycin C-induced HUS. Therapy for mitomycin (HUS) with protein A columns should continue until circulating immune complexes reach undetectable levels and serum complement levels return to the normal range.

Anaphylaxis↗

Treatment of peritoneal carcinomatosis in patients with digestive cancers with combination of intraperitoneal hyperthermia and mitomycin C.

Peritoneal carcinomatosis in patients with digestive cancer carries a poor prognosis, with a majority of patients dying within 6 months. Mitomycin C has been reported to have some antitumor efficacy in this setting. We performed combination intraperitoneal hyperthermia and mitomycin to potentiate the effect of mitomycin C in 83 patients with peritoneal involvement due to digestive cancers. Eighty six IPCH procedures were performed using inflow temperature 46 to 49 degrees Celsius, using a closed circuit, during 90 minutes. Mitomycin C was administered as a perfusate at 10 mg/l. Primary tumors were essentially gastric (42) and colorectal (27). Mortality and morbidity rates were 3/83 and 5/83 respectively. For resectable tumors, the median survival time was 16 months in stage 1 and 2 carcinomatosis (malignant granulations less than 5 mm in diameter). For resectable gastric cancers with stage 1 and 2 carcinomatosis, one, two and three year actuarial survival rates were 80, 61 and 41% respectively. In conclusion, IPCH appears to be an interesting therapeutic option in patients with digestive cancers and small malignant peritoneal granulations (stage 1 and 2).

Adult↗

Intraoperative application of topical mitomycin C 0.05% for pterygium surgery.

BACKGROUND: Pterygium recurrence is a common problem encountered by ophthalmic surgeons. Several methods have been suggested to avoid these recurrences. We studied the recurrence rate of pterygium after administration of a single intraoperative dosage of topical mitomycin C 0.05%. METHODS: A retrospective analysis of fifty eyes in forty-nine patients who underwent pterygium excision by the same surgeon using intraoperative topical mitomycin C during the years 2002--2003. Mitomycin concentration was 0.05% applied to pterygium and adjacent areas after undermining and separation from sclera but prior to excision for three minutes. Postoperative follow up time was 12 months. RESULTS: The pterygium recurred in 4 (8%) eyes. Another four eyes (8%) had a cosmetically acceptable recurrence of < 2.0 mm. The only complication was a corneal dellen in one eye. CONCLUSION: Intraoperative administration of mitomycin C at 0.05% is safe and effective in preventing pterygium recurrences.

Administration, Topical↗

Effects of plant phenolics and grape extracts from Greek varieties of Vitis vinifera on Mitomycin C and topoisomerase I-induced nicking of DNA.

In recent years, a number of reports have shown the anticancer activity of grape extracts and wine against various types of cancer such as breast, lung and gastric cancer. This property is mainly attributed to the plant polyphenols identified in grapes. The aim of the present study was to investigate the mechanisms by which grape extracts and plant polyphenols found in them exert their chemopreventive and antitumour activities. Thus, aqueous and methanolic extracts from two Greek varieties of Vitis vinifera, fractions enriched in polyphenols of these extracts and polyphenolics (caffeic acid, ferulic acid, gallic acid, protocatechuic acid and rutin) found in grapes were screened using two in vitro assays: i) the topoisomerase I relaxation assay and ii) the mitomycin C-induced DNA strand breakage. The grape extracts, the polyphenol-rich fractions and some of the polyphenolics (caffeic acid and protocatechuic acid) were potent inhibitors of topoisomerase I, indicating that the inhibition of this enzyme may be one of the mechanisms accounting for the anticancer activity of these compounds. Moreover, the grape extracts inhibited the mitomycin C-induced DNA strand breakage suggesting that they could prevent ROS-mediated DNA damage. On the other hand, the polyphenol-rich fractions and the plant polyphenols enhanced the mitomycin C-induced DNA strand breakage indicating prooxidant activity. Thus, it is of interest that whole grape extracts act as chemopreventive agents by inhibiting topo I and mitomycin C-induced DNA damage, while polyphenol enriched fractions and plant polyphenolics exert prooxidant activity leading to enhancement of DNA damage which may account for the cytotoxic and apoptosis-inducing properties of plant polyphenols against cancer cells.

DNA Damage↗

[Clinical study in combining application of mitomycin and amnion transplantation together with pterygium resection].

PURPOSE: The aim of this study was to evaluate the effectiveness and safety of combining application of mitomycin and/or amnion transplantation when carrying out pterygium resection. METHODS: Pterygium resection, mitomycin application and amniotic membrane transplantation were carried out in three combinations: Pterygium resection plus local application of mitomycin C (MMC group, n=114), Pterygium resection plus amnion transplantation (AMT group, n=119) and Pterygium resection plus mitomycin C application and amniotic membrane transplantation (combined group, n=127). The patients were followed up for 6-18 months. The healing time, the cases of recurrence and complication were recorded and analysed. RESULTS: As for the recurrence rate, it seems that the rate in the combination group (0.79%) was smaller than that in other two groups (5.26% and 6.72%), but the difference between them was insignificant. The patients in the AMT group and in the combined group recovered faster than those in the MMC group. The healing time of the wound in the MMC group (10 +/- 2.8)d was longer than that in the AMT group (4.8 +/- 2.1) d, (P < 0.001) and that in the combined group (5.0 +/- 2.3)d, (P < 0.001). The complication rate of defect at corneal epithelium in the MMC group (10.5%) was significantly higher than that in the AMT group (0%; x2 = 13.2, P < 0.001) and that in the combined group (0.8%; x2 = 211.2, P < 0.001). The hyperemia of conjunctiva and irritation symptoms in eye in the MMC group were more serious than those in other two groups (P < 0.001). CONCLUSION: Combining application of MMC and AMT together with Pterygium resection decrease the rate of complications, eases the irritation symptoms, facilitates the recovery from the operation and may decrease the recurrence of the disease.

Aged↗

Postoperative mitomycin-C eye drop and beta radiation in the treatment of pterygia.

One hundred and forty-seven eyes (137 patients) with primary pterygia were treated with excision with additional therapy, and were followed up for three months to six years after treatment. Of 85 eyes that underwent excision and postoperative instillation of 0.02 per cent mitomycin-C, there were three which had corneal recurrence (3.5%) and four had conjunctival recurrence (4.7%). The other 62 eyes were treated with beta radiation, there were nine with corneal recurrence (14.5%) and three had conjunctival recurrence (4.8%). Adjunctive therapy with mitomycin-c eye drop reduced the recurrence rate significantly (P less than 0.1). Complications occurred in five eyes (6%) by using mitomycin-c eye drop which included allergic reaction, granulation mass and mild scleral necrosis. Two of 62 eyes (3%) treated with beta radiation had complications of granulation mass. We found that pterygium excision with mitomycin-c eye drop to be effective in prevention of recurrent pterygium.

Adult↗

Enhancement of the in vitro and in vivo antitumor activities of phosphorylated mitomycin C and etoposide derivatives by monoclonal antibody-alkaline phosphatase conjugates.

Alkaline phosphatase (AP) was covalently linked to the two antitumor monoclonal antibodies, L6 (anticarcinoma) and 1F5 (anti-B lymphoma), forming conjugates that could bind to antigen-positive tumor cells. The conjugates were able to convert the prodrugs, mitomycin phosphate (MOP) and etoposide phosphate (EP), into an active mitomycin C derivative, mitomycin alcohol, and etoposide, respectively. MOP and EP were less toxic to cultured cells from the H2981 lung adenocarcinoma than their respective hydrolysis products, mitomycin alcohol and etoposide, by a factor greater than 100, and they were also less toxic in mice. Pretreatment of H2981 cells with L6-AP greatly enhanced the cytotoxic effects of MOP and EP, while 1F5-AP caused no such enhancement. A strong antitumor response was observed in H2981-bearing mice that were treated with L6-AP followed 24 h later by either MOP or a combination of MOP and EP. This response was superior to that of MOP or combinations of MOP and EP given alone.

Adenocarcinoma↗

Generation of reactive oxygen radicals through bioactivation of mitomycin antibiotics.

Mitomycin C (MC) is a naturally occurring anticancer agent which has been shown to be more cytotoxic to hypoxic tumor cells than to their aerobic counterparts. The mechanism of action of this agent is thought to involve biological reductive activation, to a species that alkylates DNA. A comparison of the cytotoxicity of MC to EMT6 tumor cells with that of the structural analogues porfiromycin (PM), N-(N',N'-dimethylaminomethylene)amine analogue of mitomycin C (BMY-25282), and N-(N',N'-dimethylaminomethylene)amine analogue of porfiromycin (BL-6783) has demonstrated that PM is considerably less cytotoxic to aerobic EMT6 cells than MC, whereas BMY-25282 and BL-6783 are significantly more toxic. The relative abilities of each of these compounds to generate oxygen free radicals following biological activation were measured. Tumor cell sonicates, reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase, xanthine oxidase, and mitochondria were used as the biological reducing systems. All four mitomycin antibiotics produced oxygen radicals following biological reduction, a process that may account for the aerobic cytotoxicity of agents of this class. The generation of relative amounts of superoxide and hydroxyl radical were also measured in EMT6 cell sonicates. BMY-25282 and BL-6783 produced significantly greater quantities of oxygen free radicals with the EMT6 cell sonicate, reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase, and mitochondria than did MC and PM. In contrast, BMY-25282 and BL-6783 did not generate detectable levels of free radicals in the presence of xanthine oxidase, whereas this enzyme was capable of generating free radicals with MC and PM as substrates. MC consistently produced greater amounts of free radicals than PM with all of the reducing systems. BMY-25282, BL-6783, and MC all generated hydroxyl radicals, while PM did not appear to form these radicals. The findings indicate that a correlation exists between the ability of the mitomycin antibiotics to generate oxygen radicals and their cytotoxicity to aerobic EMT6 tumor cells.

Animals↗

Synergistic effect of recombinant interleukin-2 on the inhibition of growth of adenocarcinoma 755 by mitomycin.

The increase in life-span (ILS) of tumor-bearing mice caused by recombinant interleukin-2 (RIL-2) was studied in the solid tumor adenocarcinoma 755 system. With long-term treatment (Days 5-12), RIL-2 (10(5) U/mouse) showed a weak effect (24% ILS), but short-term RIL-2 treatment (Days 5-8 or 9-12) had hardly any effect. Mitomycin, at 2 mg/kg (maximum nontoxic dose), caused 35% ILS with Days 5-8 treatment and only 12% ILS with Days 9-12 treatment. Sequential treatment with mitomycin (Days 5-8) and RIL-2 (Days 9-12) markedly enhanced antitumor activity (88% ILS). This value is significantly greater than that of mitomycin alone or RIL-2 alone (P less than 0.01). Furthermore, mitomycin followed by RIL-2 markedly augmented killing activity of spleen cells that are cytotoxic in vitro. These results indicate that RIL-2 markedly affects the inhibition of growth of a tumor treated with an antitumor agent.

Adenocarcinoma↗

A review of mitomycin regimens in advanced breast cancer therapy.

Mitomycin is one of the most effective single agents in the treatment of advanced breast cancer. Recent studies have also shown that combination regimens including mitomycin are effective as initial therapy in advanced breast cancer. In patients with advanced disease who fail to respond to initial chemotherapy, a combination regimen including mitomycin is as effective as the other combinations currently used in salvage therapy. A combination of mitomycin and a drug such as doxorubicin or vinblastine produces results equivalent to those reported with regimens more commonly used. Such a combination is a therapeutic alternative in patients with advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Combination chemotherapy for non-small cell lung cancer with doxorubicin and mitomycin or cisplatin and etoposide.

The combinations of doxorubicin (40 mg/m2 iv every 3 weeks) and mitomycin (12 mg/m2 iv every 6 weeks) or cisplatin (80 mg/m2 iv every 3 weeks X 3, then every 6 weeks) and etoposide (80 mg/m2 iv on Days 1-3 every 3 weeks X 3, then every 6 weeks) were evaluated in a randomized phase II trial in 77 patients with measurable or evaluable non-small cell lung cancer. No patient had been pretreated with prior chemotherapy. The overall response rate for the doxorubicin and mitomycin regimen was 11% and for the cisplatin and etoposide regimen was 23%. Responses lasted a median of 5.5 months. Median survival was 7.0 months for the doxorubicin and mitomycin regimen and 8.0 months for the cisplatin and etoposide regimen. One treatment-related death was observed after doxorubicin and mitomycin in a patient who had received radiation therapy immediately prior to study entry. Otherwise, the hematologic toxicity of both chemotherapy regimens was moderate, with only six patients (10%) having World Health Organization grade 3 toxicity and no patients having World Health Organization grade 4 toxicity. However, subjective tolerance gastrointestinal upset) of the cisplatin and etoposide combination was poor.

Adenocarcinoma↗

[Chemotherapy-induced hemolytic uremic syndrome. A complication to mitomycin treatment of breast carcinoma].

Mitomycin is a cytotoxic antibiotic that was first introduced into clinical use in 1958. Not until twenty years later was it recognised that haemolytic uremic syndrome could develop after treatment with mitomycin. It can be asked whether this condition was undiagnosed in previous years, since its frequency is now reported to be 4-15%. The disease appears to be dose-related, since it rarely occurs in patients who have received mitomycin < 30 mg/m2. No effective therapy has been established. We describe two patients with breast cancer in remission after treatment with mitomycin in combination with 5-fluorouracil. Both developed haemolytic uremic syndrome with fatal outcome.

Adult↗

[Interstitial pneumonia and mitomycin C. Apropos of a case with analysis of the bronchoalveolar lavage].

Mitomycin C is an antibiotic used for its alkylizing effect in the treatment of broncogenic cancer. Haematologic, renal or pulmonary complications are sometimes severe. We report a case in a patient with poorly differentiated epidermoid bronchogenic carcinoma who developed clinical and radiological signs of bilateral infiltrating pneumonia due to mitomycine. This observation emphasizes the importance of bronchoalveolar lavage which implicated the immunological toxicity of mitomycine and explained the efficacity of corticosteroid treatment. Pulmonary lesions due to mitomycine were discussed.

Adult↗