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[Effect of mitomycin C dissolved in a reversible thermosetting gel on outcome of filtering surgery in the rabbit].

PURPOSE: Based on our previous report that showed enhanced transfer of mitomycin C to the sclera and the conjunctiva by dissolving the antiproliferative in a reversible thermo-setting gel, we conducted a study to investigate the efficacy of the mitomycin C-gel in the rabbit. METHODS: We subconjunctivally injected 0.1 ml of the mitomycin C-gel solution containing several amounts of the drug. Trephination was performed in the injected region 24 hours later. Intraocular pressure measurement, and photography and ultrasound biomicroscopic examination of the filtering bleb were done 1, 2, and 4 weeks postoperatively. RESULTS: The gel containing 3.0 micrograms or more mitomycin C significantly enhanced bleb formation in addition to reducing the intraocular pressure. CONCLUSION: The reversible thermo-setting gel seems to facilitate filtration following glaucoma filtering surgery in the rabbit and deserves further investigation as a new method of mitomycin C application.

Animals↗

[Subconjunctival mitomycin C for the treatment of ocular cicatricial pemphigoid].

PURPOSE: We study the efficacy of treating ocular cicatricial pemphigoid (OCP) with subconjuctival mitomycin C (MMC). METHODS: The patients were eligible for treatment under two criteria: 1. Significant complications of systemic immunosuppressant therapy. 2. Avanced stage of OCP. All patients received an injection of 0.25 ml of 0.2 mg/ml mitomycin C to both the upper and lower bulbar conjunctiva in both eyes. RESULTS: Four patients were treated with subconjunctival mitomycin C (both eyes) and were followed for an average of 17 months (range 9-26 months). Three of four patients showed progression of the conjunctival disease and required concomitant systemic immunosuppressive therapy after subconjuctival mitomycin C. CONCLUSION: No complications of subconjunctival mitomycin C treatment were noted but, contrary to what other authors had referred, its use was not effective in preventing progression of conjunctival cicatrization in our patients with OCP.

Aged↗

Evaluation of the effect of mitomycin-C on the bioavailability of technetium-99m-labelled sodium pyrophosphate in mice.

We have reported that drugs alter the biodistribution of radiopharmaceuticals used in diagnostic imaging in nuclear medicine. Knowledge of such altered biodistribution is important in making diagnostic from scintigraphy. Mitomycin-C is used as component of many chemotherapeutic regimens to treat different tumors. The biological activities of mitomycin-C can be explained by its ability to inhibit deoxyribonucleic acid synthesis. Since patients on chemotherapeutic treatment can be submitted to nuclear medicine procedures, we studied the mitomycin-C effect on the bioavailability of the technetium-99m-labelled sodium pyrophosphate (9mTc-PYP) using an animal model. Mitomycin (0.45 mg) was administered by ocular plexus way Balb/c mice. One hour after the last dose, 99mTc-PYP (7.4 MBq) was administered and after 0.5 hr the animals (n = 15) were rapidly sacrificed. The organs were isolated, the radioactivity counted in a well counter and the percentage of radioactivity (%ATI) calculated. The results have shown that in the treated animals the %ATI has been decreased in spleen, thymus, heart and brain and increased in lung, liver and bone. The effect of this chemotherapeutic drug on the 99mTc-PYP biodistribution was statistically significant (Wilcoxon test, p < 0.05) and it could be explained by the metabolization or therapeutic action of mitomycin-C.

Animals↗

Rationale for mitomycin and irinotecan use in advanced breast cancer.

For women who develop hormone-refractory metastatic breast cancer, or who have breast cancers that are not estrogen-dependent (hormone receptor-negative), treatment with chemotherapy is the best option. Mitomycin (Mutamycin) and irinotecan (CPT-11, Camptosar) have marginal activity in breast cancer. However, the sequential administration of mitomycin and irinotecan appears to have synergism in preclinical studies, as mitomycin upregulates the level of topoisomerase I, the target of irinotecan. A phase I clinical trial of pharmacologically based sequential administration of mitomycin on day 1 followed by irinotecan on days 2 and 8 was performed in previously treated solid tumor patients. In five heavily pretreated women with breast cancer, one patient had a complete response, one patient had a partial response, and one patient had stable disease. Upregulation of topoisomerase I gene expression in peripheral blood mononuclear cells was observed in two of the responding patients. A phase II trial of mitomycin followed by irinotecan in women with previously treated metastatic, inflammatory, or locally advanced breast cancer is currently ongoing.

Antibiotics, Antineoplastic↗

Intraoperative use of mitomycin C in fibrous atresia of the external auditory canal.

The ability of mitomycin C to inhibit fibroblasts in vitro has prompted its use during standard surgical procedures as a means of preventing the development of adhesions and stenosis. We conducted a prospective study to evaluate the effectiveness of topical mitomycin C in maintaining an open external auditory canal in 6 ears of 4 patients with aural fibrotic atresia who were undergoing meatoplasty. During the procedure, we applied 1 ml of mitomycin C (0.4 mg/ml) for 4 minutes to the external auditory canal (in 1 case, mitomycin C was reapplied to an ear 1 month later). Between 3 and 14 months postoperatively, the patency of the ear canal was assessed visually and hearing was evaluated audiometrically. Adequate patency was achieved in 5 of the 6 ears (83.3%), and the air-bone gap in these 5 ears had improved to 10 dB or less. No postoperative complications or sensorineural hearing loss was observed. In this very limited number of cases, we found that the intraoperative use of mitomycin C appeared to have been helpful in preventing scarring in both congenital and secondary fibrotic atresias of the external auditory canal. These preliminary results are encouraging, and a prospective, placebo-controlled study appears to be warranted.

Adult↗

[Morphological and biochemical characteristics of Streptomyces hygroscopicus mutants obtained under the action of acridine orange and mitomycin C].

The purpose of this work was to study the action of acridine orange and mitomycin C on the production of mutants of Streptomyces hygroscopicus, strain 0681. The mutagen activity of mitomycin C was shown to be high. The vegetative culture grown for 24 hours produced more mutants under the action of mitomycin C than spores did. Both acridine orange and mitomycin C caused the production of mutants in strain 0681. The morphology of colonies in these mutants was modified, the synthesis of hygromycin B was completely or partly blocked, and the composition of fatty acids changed quantitatively and qualitatively. Mutants induced by mitomycin C were highly active in the production of the complex of hygrolytin proteolytic enzymes.

Acridine Orange↗

Sister chromatid exchanges in lymphocytes of cancer patients receiving mitomycin C treatment.

Peripheral lymphocytes from cancer patients receiving mitomycin C treatment were examined for cytogenetic effects. The treatment consisted of i.v. injections of mitomycin C at a dose of 4 mg given twice a week for 2 weeks. The lymphocytes were cultured in vitro for 72 hr with phytohemagglutinin and 5-bromodeoxyuridine, and then sister chromatid exchanges were scored. Before treatment with mitomycin C, the frequencies of sister chromatid exchanges in lymphocytes of cancer patients were similar to those of healthy controls. After the first and second treatments in vivo with mitomycin C, the frequencies of sister chromatid exchnages increased with time, reached a peak in about 24 hr, and then returned to the pretreatment level in about 48 hr, in contrast to the case of in vitro exposure to mitomycin C. After the third and fourth injections, however, the frequency increased further and did not return to the original level. The significance of the specific kinetics of change in the sister chromatid exchnage frequency after in vivo treatments is discussed in relation to cancer chemotherapy.

Adult↗

Studies on the mechanism of action of mitomycin C.

The in vitro formation and properties of the molecular complex between mitomycin C and native DNA were examined by means of various experimental methods; the data obtained indicate that the complex is extremely weak and that the chromophoric moiety of the antibiotic is not involved in its formation. The alkylating activity of mitomycin C was also studied using 3H-mitomycin C; while monofunctional alkylation increases almost in parallel with the concentration of the antibiotic, the difunctional alkylation, causing inter-strand cross-linkages in DNA, rapidly reaches a maximum and then remains constant even when increasing the concentration of the antibiotic and monofunctional alkylation. On the basis of these results, the currently accepted molecular model of the mitomycin--DNA interaction must be revised; a new model of this interaction is presented, which is in better agreement with the properties of mitomycin C and with the latest findings on the subject.

Alkylation↗

Phase II randomized study of paclitaxel versus mitomycin in advanced breast cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been shown to be an effective agent in the treatment of metastatic breast carcinoma. This multicenter randomized study compared paclitaxel 175 mg/m2 given as a 3-hour infusion every 3 weeks with mitomycin 12 mg/m2 given as an intravenous infusion every 6 weeks. Eighty-one patients have been randomized, and preliminary results of a planned analysis of the first 36 evaluable patients per arm are reported. Pretreatment characteristics were well balanced between the two groups. All patients previously have received chemotherapy for metastatic disease, and half had both adjuvant therapy and chemotherapy for metastatic disease. All but one patient previously had received anthracyclines. Of the first 81 randomized patients, 72 were evaluable for response and toxicity (four never treated, five concomitant hormonotherapy). Partial responses were seen in 17% of patients in the paclitaxel arm and 6% in the mitomycin arm (P = .14). Crossover to paclitaxel therapy following progression on mitomycin achieved an objective response rate of 24% (five of 21 patients). Responses to paclitaxel therapy lasted for a median duration of 9.1 months (range, 6.2 to 12+ months). Median time to progression was significantly longer in the paclitaxel arm (3.5 months v 1.6 months; P = .026). The quality-of-life-adjusted analysis confirmed the advantage of paclitaxel therapy, even when the delay of disease progression was adjusted for important adverse events. Adverse events, most importantly neutropenia and neuropathy, were more frequently observed in the paclitaxel arm. However, patients remained on paclitaxel therapy for many more courses than did those treated in the mitomycin arm. In conclusion, paclitaxel 175 mg/m2 given as a 3-hour intravenous infusion has been demonstrated to be an active agent in the treatment of chemotherapy-refractory advanced breast cancer, even after therapy with mitomycin has failed.

Adult↗

[Trabeculectomy with mitomycin C. Study apropos of 30 cases].

UNLABELLED: Standard trabeculectomy with adjunct Mitomycin C application was performed in 30 eyes of 26 patients with refractory glaucoma to study the efficacy and safety of this technique. The results were analyzed for each aetiology and number of ocular risk factors for failure of filtering procedure and compared with those of other series, including those using 5-fluorouracil. METHODS: The surgical procedure was similar to that described by Cairns, except that a fornix-based conjunctival flap was used. A 0.4 mg/ml solution of Mitomycin C was applied at the filtration site for three minutes. The mean follow-up was 6.4 months; the thirty eyes were followed for 4 to 11 months. RESULTS: At 6 months, the intraocular pressure was less than 21 mmHg in 65.2% of cases without postoperative glaucoma medication, and the overall success rate was 86.9%. No remarkable complications occurred. CONCLUSION: Intraoperative Mitomycin C may be a helpful adjunct in achieving low final intraocular pressure after trabeculectomy in high-risk glaucoma filtering surgery, and Mitomycin C may be a viable alternative to postoperative 5-Fluorouracil. But further studies regarding late complications due to mitomycin are required.

Adolescent↗

Ocular toxicity of mitomycin C and 5-fluorouracil in the rabbit.

We studied the histotoxic effects of mitomycin C and 5-fluorouracil (5-FU) in the eyes of New Zealand white rabbits using light microscopy. Twenty-four eyes of 24 rabbits received subconjunctival injections of mitomycin C (0.025, 0.05, 0.10, 0.20, 0.40 or 0.80 mg/mL) or 5-FU (10.0 mg/mL), either alone (0.25 mL) or in combination with anterior chamber injections (0.05 mL), once daily for 4 consecutive days. Two eyes of two rabbits received subconjunctival and anterior chamber injections of unpreserved sterile saline. The eyes were examined regularly for external signs of toxicity and were enucleated 4 weeks after the last injection. Mitomycin C produced considerable tissue damage in the anterior segment, the severity being related to both the concentration and the route of administration. Eyes that received both subconjunctival and anterior chamber injections showed more damage than those that received subconjunctival injections alone. At the highest concentration of mitomycin C the cornea was inflamed, with stromal necrosis and marked endothelial loss. Hemorrhagic iris necrosis was also seen. In contrast, the 5-FU-treated eyes showed no microscopic evidence of toxicity. We conclude that there is greater risk of toxic anterior segment effects when mitomycin C is used as adjunctive therapy following filtration or pterygium surgery.

Animals↗

Holmium laser sclerostomy via corneal approach with transconjunctival mitomycin-C in rabbits.

We studied the use of the holmium laser for sclerostomy through a small lamellar corneal incision and the effects of transconjunctival mitomycin-C on the outcome of filtration surgery without conjunctival incision. The holmium laser, equipped with a straight-firing probe, was used to create sclerostomies in seven New Zealand white rabbits through a corneal lamellar incision. One eye in each rabbit was treated with transconjunctival mitomycin-C (0.4 micrograms/mL for 5 minutes), and the fellow eye underwent sclerostomy without pretreatment with mitomycin-C as a control. The reduction in intraocular pressure was greater and persisted significantly longer in the eyes pretreated with mitomycin-C than in the controls. All control eyes had flat blebs by day 7 to 12, while the treated eyes maintained a bleb throughout the study. Microscopic examination showed that sclerostomies created by the straight-firing probe induced significantly less thermal damage than those created by the stationary side-firing probe. These results demonstrate that successful transcorneal sclerostomy without conjunctival incision can be created using the straight-firing holmium laser probe, with enhancement of filtration by pretreatment with transconjunctival mitomycin-C.

Animals↗

Indications for and complications of mitomycin-C in pterygium surgery.

BACKGROUND AND OBJECTIVE: The purposes of this study are to examine the complications and results of a novel approach to the use of mitomycin-C in pterygium surgery; to identify the lowest effective dosage required to prevent recurrence; and to select those high-risk pterygia that could benefit from mitomycin-C use. PATIENTS AND METHODS: One hundred thirty-five eyes of 128 patients considered at high risk for recurrence of pterygium were treated with a single, intraoperative, subconjunctival injection of mitomycin-C at the site of excision. Three different dosages-0.2, 0.1, and 0.05 ml-at a strength of 0.5 mg/ml were used. The eyes were observed for 10 months to 3 years. RESULTS: There were only two recurrences (1.5%); both occurred in eyes that had undergone previous pterygium surgery. One recurrence happened with the 0.2-ml dosage, and the other with the 0.1-ml dosage. These recurrences occurred in association with early wound dehiscence, which essentially became a bare sclera susceptible to pterygium regrowth. Complications included temporary and prolonged discomfort, tearing, hyperemia, subconjunctival hemorrhage, wound dehiscence, and pigment accumulation. No vision-threatening side effects were noted. CONCLUSIONS: The persistence and intensity of discomfort noted at the higher dosage has prompted these authors to suggest that only high-risk pterygia should receive mitomycin-C. Conjunctival flaps should always be used to cover the sclera up to the limbus and to localize the mitomycin-C to prevent its migration. A single dose of not more than 0.05 ml at a strength of 0.5 mg/ml subconjunctivally gives the same results as multiple drops, but with far less morbidity.

Adolescent↗

Late bleb leakage after trabeculectomy with 5-fluorouracil or mitomycin C.

OBJECTIVE: To determine the prevalence of late filtering bleb leakage after trabeculectomy performed with intraoperative adjunctive use of 5-fluorouracil (5-FU) or mitomycin C. DESIGN: Case series. SETTING: Private clinic in São Paulo. PATIENTS: Forty-seven consecutive patients (47 eyes) who had previously undergone trabeculectomy with intraoperative application of either 5-FU (25 mg/mL) or mitomycin C (0.2 mg/mL) and who had functioning filtering blebs. The patients who received 5-FU had advanced primary open-angle glaucoma without previous surgery; those who received mitomycin C had either previous failed filtering surgery or refractory glaucoma. All patients had been followed for at least 6 months. OUTCOME MEASURES: Slit-lamp appearance of bleb, bleb leakage, as determined with the Seidel test. RESULTS: None of the eyes had spontaneous bleb leakage. Ten (32.2%) of the 31 eyes that received 5-FU and 5 (31.2%) of the 16 eyes that received mitomycin C had induced bleb leakage. Thirty filtering blebs were classified as transparent, 10 as vascularized and 7 as ischemic. The rates of bleb leakage for the three groups were 46.7%, 0% and 14.3% respectively (p = 0.012). CONCLUSIONS: The importance of late bleb leakage in patients who receive intraoperative 5-FU or mitomycin C in predisposing these eyes to late complications, such as endophthalmitis and hypotony, needs to be evaluated.

Adult↗

Postoperative instillation of 0.04% mitomycin C in the treatment of primary pterygium in Zaire.

PURPOSE: to investigate, in the first report in Central Africa, the influence of tropical Mitomycin C on the recurrence rate and on the complications after surgical treatment for primary pterygium. METHODS: Sixty-six patients with primary pterygia underwent excision of the lesion, leaving the sclera bare. Patients were randomized in two groups: in one group (36 eyes in 33 patients) 0.04% mitomycin C eye drops were used four times daily during two weeks or longer after surgery, the other group (41 eyes in 33 patients) underwent only surgery. The mean follow-up period was 6 months (range, one to 24 months). RESULTS: seven (19.4%) pterygia recurred in the group of eyes treated with topical 0.04% mitomycin C and 11 (26.8%) in the group of eyes treated without this drug. This difference was not significant (p > 0.05). Complications were observed in two (5.6%) eyes in group 1 and included conjunctival granuloma (one eye) and transient ocular hypertension. In group 2, complications were noted in four eyes (9.8%) and included conjunctival granulomas (three eyes) and symblepharon (one eye). Ocular hypertension could be due to instillation of mitomycin C. No group had significantly more complications. CONCLUSION: primary excision of pterygium with postoperative instillation of 0.04% mitomycin C had a higher rate of occurrence in this study than previously reported in Japan, in the USA and Europe.

Antibiotics, Antineoplastic↗

Nanophthalmic uveal effusion managed with scleral windows and topical mitomycin-C.

The authors treated a 38-year-old man with nanophthalmic uveal effusion with scleral windows and local application of mitomycin-C. The patient underwent two separate surgical procedures, involving placement of scleral windows in all four quadrants and topical application of mitomycin-C in one quadrant. Episcleral scarring led to closure of scleral windows in all quadrants except one quadrant where mitomycin-C was applied during the first surgery. The uveal effusion resolved following the second surgery. No complications related to mitomycin-C were observed. Topical mitomycin-C may be a useful adjunct in the surgical management of uveal effusion syndrome.

Administration, Topical↗

Simultaneous use of mitomycin-C with Baerveldt implantation.

BACKGROUND AND OBJECTIVE: To evaluate the outcome of Baerveldt implantation with adjunctive mitomycin-C in cases of complicated glaucoma. PATIENTS AND METHODS: The authors reviewed the charts of all patients who had undergone Baerveldt implantation with mitomycin-C between January 1993 and March 1995. Success was defined before data collection as an intraocular pressure (IOP) between 5 and 21 mm Hg, with or without medications. The success rate was calculated using the Kaplan-Meier actuarial method. RESULTS: Twenty-nine patients were identified. The mean preoperative IOP was 33.6 mm Hg, with an average of 2.0 antiglaucoma medications. The probability of success at 6 and 12 months for patients who received mitomycin-C during Baerveldt implantation was 82.4% and 73.3%, respectively. Choroidal effusion with a flat anterior chamber (10.3%), corneal edema (6.8%), and conjunctival erosion (6.8%) were the most frequent complications. CONCLUSION: In this retrospective series of complicated glaucoma, the implantation of a Baerveldt drainage device with adjunctive mitomycin-C had a satisfactory outcome. The complications encountered and the clinical efficacy were comparable to those of previously reported series in which mitomycin-C was not used.

Antibiotics, Antineoplastic↗

Cloning and Overexpression of the Mitomycin C Resistance Gene (mcr) from Streptoverticillium caespitosum.

Streptoverticillium caespitosum ATCC27422 is a major producer of an anti-cancer drug, mitomycin C. A 6.6 kb DNA fragment containing the mitomycin C resistance gene (mcr) was isolated from ATCC27422 by shotgun method in order to learn the molecular mechanism of mitomycin C resistance. By constructing a series of subclones from this 6.6 kb DNA fragment, the mitomycin C resistance gene was localized on a 3.1 kb DNA fragment. Sequence analysis revealed that the open reading frame of mcr gene was 1 347 bp in size, encoding 448 amino acids with ATG as initiation codon and TGA as termination codon. The mcr gene was specifically expressed under the control of T7 promoter in E.coli, and the resistance to mitomycin C in the transformant was over 100-fold higher than that in wild-type strain. The overexpression of mcr gene in E.coli is very helpful for the further research about the molecular mechanism of drug resistance.

Journal Article↗