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PubMed2006

Immediate administration of intravesical mitomycin C after tumour resection for superficial bladder cancer.

OBJECTIVE: To assess the feasibility and safety of administering intravesical mitomycin C in theatre immediately after transurethral resection of bladder tumour (TURBT). PATIENTS AND METHODS: A protocol was developed to allow the safe administration of mitomycin C in theatre immediately after TURBT. Over a 32-month period all patients not excluded by the protocol were given mitomycin C in theatre after TURBT, and any adverse events reported. RESULTS: In all, 177 instillations were carried out; there were two minor patient-related complications, and no staff-related adverse events. CONCLUSION: The immediate administration of mitomycin C in theatre after TURBT is feasible and safe for patients and staff. It provides the earliest and surest prophylaxis against tumour cell re-implantation at TURBT.

Administration, Intravesical↗
PubMed2006

Reducing recurrence and costs in superficial bladder cancer: preclinical evaluation of osmotic cytolysis by distilled water vs. mitomycin.

Transurethral resection followed by instillation of chemotherapeutic agents such as mitomycin is considered as standard therapy in recurrent superficial bladder cancer. However, incidence of bladder cancer is increasing, and contrariwise resources to finance the health care systems are decreasing. Therefore, effective alternatives to expensive chemotherapeutics are necessary. Recurrence of bladder cancer after transurethral resection is mostly promoted by reimplantation of dissolved tumour cells which are therapeutical purpose of any intravesically instillated agent. Monolayer cultures of human RT112, RT4, T24 and TCC SUP bladder cancer cells were incubated and exposed to mitomycin or distilled water. Cell survival was determined by microculture tetrazolium assay. Distilled water led to significant cytolysis in all tumour cells. This effect was comparable to exposition to mitomycin. Distilled water and mitomycin have comparable in vitro effects in bladder cancer cells. These findings have to be substantiated by an animal model emphasising the aspect of larger tumour cell compounds or possible damage to healthy bladder tissue.

Antibiotics, Antineoplastic↗
PubMed1994

The effect of brief intrascleral or episcleral application of mitomycin C on the ciliary epithelium and pressure in the rabbit eye.

Ten albino rabbits underwent bilateral Cairns' trabeculectomy (group 1). A sponge soaked with 0.5 mg/ml mitomycin C solution was applied under the scleral flap for 5 min followed by irrigation with 20 ml 0.9% sodium chloride solution in the left eyes. In the right eyes a sponge soaked with 0.9% sodium chloride solutions was applied. In 9 albino rabbits a 3 x 2 mm episcleral area at 12 o'clock position was exposed to 0.5 mg/ml mitomycin C solution on one side and to 0.9% sodium chloride solution in the contralateral eye (group 2). Five, 10 and 30 days (group 1 and 2) and 3 months (group 1) following surgery specimens of the ciliary body adjacent, beside and opposite to the site of the operation were excised and studied with light and electron microscopy. No stromal or epithelial morphological changes of toxic origin have been revealed in the ciliary processes, even in specimens adjacent to the surgical area. In 5 albino rabbits (group 3) intraocular pressure was recorded before surgery and 5, 10 and 30 days after unilateral, episcleral mitomycin C application described in group 2. No significant changes or interocular difference has been recorded. The results suggest that long-term postoperative hypotony following trabeculectomy with mitomycin C is not caused by reduced aqueous humour secretion of toxic origin.

Animals↗
PubMed2004

Nuclear localization of NADPH:cytochrome c (P450) reductase enhances the cytotoxicity of mitomycin C to Chinese hamster ovary cells.

Overexpression of endoplasmic reticulum-localized NADPH: cytochrome c (P450) reductase (NPR) in Chinese hamster ovary cells increases the hypoxic/aerobic differential toxicity of the mitomycins. Because considerable evidence indicates that DNA cross-links are the major cytotoxic lesions generated by the mitomycins, we proposed that bioactivation of the mitomycins in the nucleus close to the DNA target would influence the cytotoxicity of these drugs. The simian virus 40 large T antigen nuclear localization signal was fused to the amino-terminal end of a human NPR protein that lacked its membrane anchor sequence. Immunofluorescent imaging of transfected cell lines expressing the fusion protein confirmed the nuclear location of the enzyme. Regardless of the oxygenation state of the cell, mitomycin C (MC) cytotoxicity was enhanced in cells with overexpressed NPR localized to the nuclear compartment compared with cells overexpressing an endoplasmic reticulum localized enzyme. Enhanced cytotoxicity in cells treated under hypoxic conditions correlated with increases in genomic DNA alkylations, with more MC-DNA adducts being formed when the enzyme was expressed closer to its DNA target. No change was observed in the hypoxic/aerobic differential toxicity as a function of enzyme localization. These findings indicate that drug efficacy is increased when the subcellular site of drug activation corresponds to its site of action.

Active Transport, Cell Nucleus↗
PubMed1981

Influence of cultural conditions on mitomycin C-mediated bacteriophage induction and release of Salmonella toxin.

Several isolates of Salmonella were examined for the capacity to synthesize and release a cholera toxin-like toxin that exerted a biological effect on Chinese hamster ovary cells. Measurements of this Salmonella toxin, which was contained in cell sonic extracts and culture filtrates, were expressed in cholera toxin equivalents (nanograms), since the Chinese hamster ovary cell responses of the cholera toxin and the Salmonella toxin were indistinguishable. Comparative titrations of Salmonella preparations were also performed by using an enzyme-linked immunosorbent assay specific for cholera toxin antigen. The amount of Salmonella toxin synthesized was low (nanogram levels), but the toxin was detectable in cell sonic extracts as early as 6 h after culture inoculation and reached maximal levels by 12 h. Salmonella toxin antigen was not detectable in control culture filtrates until 48 h, but the addition of mitomycin C at 8.5 h resulted in the sudden appearance of toxin antigen at 10 to 12 h, and the toxin antigen level reached a maximum at 14 h. A large peak of Chinese hamster ovary cell activity was observed at 48 h in the control culture, but significant Chinese hamster ovary cell activity was detected as early as 14 h. A larger amount of Chinese hamster ovary cell-reactive material was observed as early as 10 h in cultures grown with mitomycin C. The mechanism of the mitomycin-mediated phenomenon that yielded more toxin in culture filtrates was associated with bacteriophage induction. A bacteriophage plaque assay with a susceptible Salmonella strain revealed that there were free bacteriophage in mitomycin-treated culture filtrates (but not control culture filtrates) at 12 h. Toxin production was greatest when cultures were grown at 30 to 37 degrees C and lowest when cultures were grown at 25 degrees C. The inoculum size and degree of culture aeration (agitation) had little effect on synthesis of the toxin, and toxin production occurred during anaerobic growth.

Aerobiosis↗
PubMed1999

Mitomycin resistance in Streptomyces lavendulae includes a novel drug-binding-protein-dependent export system.

Sequence analysis of Streptomyces lavendulae NRRL 2564 chromosomal DNA adjacent to the mitomycin resistance locus mrd (encoding a previously described mitomycin-binding protein [P. Sheldon, D. A. Johnson, P. R. August, H.-W. Liu, and D. H. Sherman, J. Bacteriol. 179:1796-1804, 1997]) revealed a putative mitomycin C (MC) transport gene (mct) encoding a hydrophobic polypeptide that has significant amino acid sequence similarity with several actinomycete antibiotic export proteins. Disruption of mct by insertional inactivation resulted in an S. lavendulae mutant strain that was considerably more sensitive to MC. Expression of mct in Escherichia coli conferred a fivefold increase in cellular resistance to MC, led to the synthesis of a membrane-associated protein, and correlated with reduced intracellular accumulation of the drug. Coexpression of mct and mrd in E. coli resulted in a 150-fold increase in resistance, as well as reduced intracellular accumulation of MC. Taken together, these data provide evidence that MRD and Mct function as components of a novel drug export system specific to the mitomycins.

Amino Acid Sequence↗
PubMed1967

Effects of mitomycin C on macromolecular synthesis in Escherichia coli.

When cells of Escherichia coli B growing in a glucose-synthetic medium were treated with mitomycin C, the effects produced by the antibiotic varied, depending on the concentration. When the concentration was reduced to less than 0.1 mug/ml, the action of the antibiotic was bacteriostatic; cell elongation resulted, but no effect on the synthesis of cellular macromolecules was apparent. At higher levels (more than 5 mug/ml), mitomycin C was highly bactericidal and inhibited deoxyribonucleic acid synthesis almost completely. The exposure of growing cells to a bactericidal level of mitomycin C resulted also in a delayed inhibition of the synthesis of ribonucleic acid (RNA) and protein. The capacity of the treated cells to synthesize beta-galactosidase inducibly in a medium free from a carbon source remained constant for the first 30 min and then was destroyed progressively with time. Prolonged incubation with the bactericidal level of mitomycin C caused a degradation of cellular nucleic acids, particularly RNA. The degraded nucleic acid components were eventually released into the medium.

Bacterial Proteins↗
PubMed1967

Filamentous cells of Escherichia coli formed in the presence of mitomycin.

The effects of mitomycin C on cell elongation of Escherichia coli B were studied. Filament formation was most marked in cultures treated with a moderate level (1 mug/ml) of the antibiotic, becoming less obvious at higher levels (10 mug/ml). Cells treated with a bacteriostatic concentration (0.1 mug/ml or less) of mitomycin C were also significantly elongated. The filamentous or elongated cells appeared to lack septa, since their spheroplasts were considerably larger than those formed from normal cells. The appearance of empty spheres also indicated some defects in the surfaces of the filamentous cells. Electron micrographs of the filaments revealed a characteristic difference in the arrangement of the nuclei in the filaments formed in the presence of low (0.1 mug/ml) and high (5 mug/ml) concentrations of mitomycin C. The filaments formed by the low level of mitomycin C had normal well-defined nuclear bodies distributed along the long axis, whereas those formed by the elevated level of the antibiotic contained smaller nuclei. The latter were characteristically confined to the center of the cells and did not extend out to the tips of the filaments.

Cell Nucleus↗
PubMed1967

Effects of mitomycin C and thymidine deprivation on lysogenic and sensitive strains of Bacillus megaterium.

A triple auxotroph of Bacillus megaterium strain KM was lysogenized with a phage suspension from B. megaterium 899a. The lysogenic and phage-sensitive derivatives of KM were found to die at the same exponential rate during thymineless incubation, despite the fact that the lysogenic strain became induced. The lysogenic strain was also induced by mitomycin C, and died at an exponential rate which was approximately twice that of the sensitive strain. With both strains, the lethality of mitomycin C was the same in the presence and absence of thymidine; thymidine was required for maximal phage production. Mitomycin C preferentially inhibited deoxyribonucleic acid (DNA) synthesis of both strains for the first 60 min. The (DNA) synthetic ability of the lysogenic strain was subsequently restored, due to phage production. Since there was no evidence that sensitive strains of KM contained other inducible elements (prophage or probacteriocins), it is concluded that both thymineless death and mitomycin C death can occur via mechanisms not involving induction.

Bacillus megaterium↗
PubMed1993

Mitomycin immunoblot colony assay for detection of Shiga-like toxin-producing Escherichia coli in fecal samples: comparison with DNA probes.

We developed a direct screening immunoblot assay for the detection of Shiga-like toxin (SLT)-producing organisms in stool samples. The assay takes advantage of the phage-mediated nature of SLT production in Escherichia coli and the phage-inducing effects of mitomycin. The addition of mitomycin significantly enhanced the amount of toxin available for immunologic detection. By using the mitomycin-enhanced immunoblot assay, SLT-producing E. coli could be distinguished from non-toxin-producing E. coli and normal stool flora in ratios of 1:1,000 to 1:5,000. The immunoblot assay was examined in a field setting and compared with direct DNA probing for SLT-I and SLT-II. The assay was able to detect SLT-producing E. coli with a high level of sensitivity and specificity. Specificity was markedly improved by using a monoclonal antibody which cross-reacts with both SLT-I and SLT-II B subunits in place of the polyclonal antitoxin sera. We conclude that the mitomycin-enhanced immunoblot colony assay is a rapid and reliable alternative to DNA probing for the detection of phage-mediated SLT-producing organisms in stool samples, especially when the production and use of nucleic acid probes are not feasible. In addition, it permits isolation of positive colonies for further study and confirmation.

Animals↗
PubMed1996

Mitomycin against posterior capsular opacification: an experimental study in rabbits.

AIMS/BACKGROUND: Posterior capsular opacification is the most common postoperative complication of extracapsular cataract surgery. The purpose of this study was to attempt to inhibit this secondary cataract formation by using mitomycin (an antimitotic drug). METHODS: A solution containing mitomycin was used to perform hydrodissection (with a 5 minute pause) during extracapsular lens extraction in rabbits. This way of administration was chosen to reduce as much as possible drug diffusion into the anterior chamber. Heparin was added to the irrigating solution to avoid fibrin formation. Its ability to prevent posterior cataract opacification was also evaluated at the end of the study. The animals were sacrificed 4 or 6 months after surgery. Grading concerning two aspects of secondary cataract (proliferation and fibrosis) was obtained on gross examination. Histological analysis was subsequently performed. RESULTS: This study demonstrated that mitomycin has a significant inhibitory effect on secondary cataract formation (proliferation as well as fibrosis) in rabbits whereas heparin does not seem to have the same effectiveness. CONCLUSION: This work is a preliminary study concerning the use of mitomycin for prevention of posterior capsular opacification. It has proved its effectiveness in rabbits but more in depth studies are still necessary before its application in humans.

Animals↗
PubMed1998

Adjunctive use of mitomycin C on endoscopic lacrimal surgery.

AIMS: Endoscopic endonasal dacryocystorhinostomy (DCR) has some advantages over external DCR as a less invasive method with no skin incisions. But the success rate of the operation has not reached the level of external method. In this study, a wound healing inhibitor mitomycin C was used intraoperatively to prevent the closure of the osteum after the operation. METHODS: Endoscopic endonasal DCR was performed on 40 eyes of 39 patients (26 female, 13 male). Mitomycin C was applied to the ostium in 14 of 23 patients who had undergone primary endoscopic DCR by means of a microdrill and in eight of 17 patients who had a revision endoscopic DCR secondary to a previously failed external DCR. RESULTS: The postoperative follow up period was 9-27 (mean 18.2) months. The success rate of endoscopic DCR with intraoperative mitomycin C was 77.3%, whereas the success rate of endoscopic DCR without mitomycin C was 77.8%. The statistical analysis did not show a difference between the two groups according to the ostium size and their success rates. CONCLUSIONS: Adjunctive use of a wound healing inhibitor is considered to increase the success rate of endoscopic endonasal DCR. Its intraoperative use seems to be easy and safe. But the study of this limited series shows no benefit in using it.

Adult↗
PubMed1998

Meta-analysis on the recurrence rates after bare sclera resection with and without mitomycin C use and conjunctival autograft placement in surgery for primary pterygium.

BACKGROUND/AIMS: Bare sclera resection with and without use of mitomycin C and conjunctival autograft placement are three surgical techniques currently in use for the treatment of primary pterygium. The purpose of this study was to determine through a meta-analysis the risk for postoperative pterygium recurrence comparing the three surgical treatment modalities. METHODS: A search through Medline for randomised controlled clinical trials comparing at least two of the three surgical techniques in the treatment of primary pterygium, along with a hand search of all references in relevant papers, was conducted. All eligible clinical trials were graded for quality utilising the Detsky score; those studies with a score of 0.5 or greater were included. The main outcome measurements were the pooled odds ratios and 95% confidence intervals for the risk of pterygium recurrence. These were calculated utilising the Mantel-Haenszel method. RESULTS: Five eligible studies with an adequate quality score were retrieved, three comparing bare sclera resection with and without mitomycin C use, one comparing bare sclera resection with conjunctival autograft placement, and one comparing both. The pooled odds ratio for pterygium recurrence in patients who had only bare sclera resection was 6.1 (95% confidence intervals, 1.8 to 18.8) compared with the patients who had conjunctival autograft placement and 25.4 (9.0 to 66.7) compared with the patients who received mitomycin C. CONCLUSIONS: The odds for pterygium recurrence following surgical treatment of primary pterygium are close to six and 25 times higher if no conjunctival autograft placement is performed or if no intra/postoperative mitomycin C is used, respectively. Surgeons and clinical triallists should not be encouraged in the use of bare sclera resection as a surgical technique for primary pterygium.

Adult↗
PubMed2001

Thermo-chemotherapy and electromotive drug administration of mitomycin C in superficial bladder cancer eradication. a pilot study on marker lesion.

OBJECTIVE: To assess the feasibility and safety of two novel methods for intravesical chemotherapy administration in patients suffering from superficial bladder carcinomas. To draw preliminary considerations concerning the ablative effect on marker lesion using novel approaches compared to standard intravesical chemotherapy. METHODS: Eighty patients suffering from single, recurrent, low-stage, low-grade superficial bladder tumor entered a prospective nonrandomized study. Thirty-six of them were treated by means of mitomycin C instillation as a standard procedure. In 29 patients mitomycin C solution was administered in combination with local microwave-induced hyperthermia and in 15 patients the mitomycin C solution was administered according to the electromotive drug procedure. The treatment was scheduled as a short term neo-adjuvant regimen prior to transurethral resection. Feasibility and safety of the different procedures were evaluated on an outpatients basis. The local toxicity induced by different approaches was defined and compared using a subjective questionnaire. RESULTS: Both intravesical chemotherapy administered in combination with hyperthermia and according to the electromotive drug technique appeared to be feasible and safe. Local toxicity induced by thermo-chemotherapy was more severe than that registered for electromotive drug technique and standard intravesical chemotherapy. Local toxicity was always short and self healing without early or delayed major complications. A higher complete response rate on marker lesion was observed after thermo-chemotherapy compared to other administration methods. CONCLUSION: The intravesical administration of mitomycin C can be safely performed in the form of both thermo-chemotherapy and electromotive drug approach with an increased ablative success rate on small superficial tumor involving only minimal local side effects.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Effects of amniotic membrane transplantation and mitomycin C on wound healing in experimental glaucoma surgery.

PURPOSE: To evaluate the effects of mitomycin C and amniotic membrane transplantation on the modulation of wound healing after glaucoma filtration surgery. METHODS: Trabeculectomy was performed in 3 groups of 10 rabbit eyes each. Sponges soaked in mitomycin C were applied to the first group, and amniotic membranes were transplanted around the scleral flap in the second group; the third group was the control. The arithmetic means of fibroblast and macrophage numbers per square centimetre were calculated. RESULTS: The mean numbers of fibroblasts and macrophages were decreased significantly in the mitomycin C group, compared with the controls (p < 0.0001). Cell counts in the amniotic membrane group were also lower than the ones in the control group for fibroblasts and macrophages (p < 0.0001, p < 0.01, respectively). The difference between the two treatment groups was statistically significant for fibroblasts (p < 0.0001), but not significant for macrophages (p > 0.05). CONCLUSION: In spite of the fact that amniotic membrane transplantation is less effective than mitomycin C for depressing wound healing after trabeculectomy, it might be a safer alternative in selected cases when considering severe adverse effects of antimetabolites.

Administration, Topical↗
PubMed1994

Effectiveness of intraoperative mitomycin C in the treatment of recurrent pterygium.

The effectiveness of intraoperative administration of mitomycin C and the occurrence of postoperative complications have been evaluated in 30 white patients with one recurrence of pterygium. The authors employed the 'bare-sclera technique' and, intraoperatively, placed in the episcleral space for 3 min a sterile sponge soaked in a 4% mitomycin C solution. The control group (30 patients with one recurrent pterygium) underwent only surgical excision. Statistical analysis performed using the chi-square test showed a significant (p = 0.024) reduction of recurrences of pterygium in the group treated intraoperatively with mitomycin C. No heavy side effects occurred during the follow-up period. Mitomycin C, administered intraoperatively, may be considered an effective treatment to improve the success rate after surgical excision.

Adult↗
PubMed2001

Mitomycin: effects on laryngeal and tracheal stenosis, benefits, and complications.

The management of laryngeal and tracheal stenosis continues to challenge us, despite advances in surgical techniques and better understanding of the wound healing process. Injury to the airway mucosa is the inciting event, regardless of the cause of the stenosis. Mitomycin-C is an antineoplastic antibiotic that acts as an alkylating agent by inhibiting DNA and protein synthesis. It can inhibit cell division, protein synthesis, and fibroblast proliferation. Topical application of mitomycin-C (0.4 mg/mL) was used as an adjuvant treatment in the endoscopic laser management of laryngeal and tracheal stenosis in 15 patients. Fourteen patients (93%) have shown improvement of their airway and resolution of their preoperative symptoms. After a mean follow-up of 18 months, no complication was noted with regard to the application of mitomycin-C. This study gives promising findings on the efficacy and safety of mitomycin-C as an adjuvant treatment in the management of selected cases of laryngeal and tracheal stenosis.

Administration, Topical↗
PubMed1999

Inhibition of subglottic stenosis with mitomycin-C in the canine model.

The objective of this randomized, prospective study was to study the efficacy of topical mitomycin-C in the inhibition of subglottic stenosis in a canine model. Subglottic stenosis was elicited with the carbon dioxide laser in 10 mongrel dogs. Radial incision and serial dilation of the subglottic airway were then carried out. The animals were randomized to receive a topical solution of 1% mitomycin-C to the dilated area for a 5-minute duration or no further treatment. Weekly direct microlaryngoscopy and photodocumentation were performed during the 6-week study. Airway distress developed in 4 of the 5 control dogs, requiring early sacrifice, while all treatment group animals survived the duration of the study (p < or = .006). Morphometric analysis of the subglottic photographs confirmed a greater than 100% increase in the percentage of relative airway at sacrifice in the treatment group (p < or = .049). A statistically significant (p < or = .015) decrease in collagen formation in the subglottic scar of dogs treated with topical mitomycin-C was documented. Mitomycin-C favorably altered the clinical progression of subglottic stenosis, improved quantified airway patency, and reduced the amount of subglottic collagen formation in the canine model.

Administration, Topical↗