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The use of mitomycin C as an adjunctive treatment for equine ocular squamous cell carcinoma.

OBJECTIVE: To assess the effectiveness of topical mitomycin C application as an alternative adjunctive therapy to CO2 laser ablation in the treatment of equine ocular squamous cell carcinoma. DESIGN: A retrospective clinical study of eight client owned horses in which 10 affected eyes were treated for ocular squamous cell carcinoma over a 17 month period. (March 2003 to August 2004). PROCEDURE: Each horse was given a general anaesthetic to allow CO2 laser ablation of the lesion(s). Mitomycin C at a concentration of 0.4 mg/mL was then applied intraoperatively to the affected areas for 1 or 5 minutes. Postoperatively a triple antibiotic eye ointment was applied to the eye twice daily and each horse was treated with systemic non-steroidal anti-inflammatory drugs for 7 days. RESULTS: Recurrence following treatment was noted in three eyes. Two of these were retreated and no further signs developed. The remaining eye was enucleated at the request of the owner. Overall 90% of treated eyes appeared free of tumour a minimum of 11 months post treatment. CONCLUSION: In this case series mitomycin C appeared to offer a valid alternative to other adjunctive therapies currently employed in the treatment of equine ocular squamous cell carcinoma.

Animals↗

In-vitro interaction of mitomycin C and streptomycin A with collagen.

Mitomycin C and streptomycin A were studied for their interaction with soluble collagens from sepia, fish and rat skins using UV absorption spectroscopy at pH 7.4 and 3.0 and equilibrium dialysis. Both the drugs bound to collagen as shown from association constants and could be quantitatively recovered by prolonged dialysis against water showing formation of dissociable bonds between drug and collagen. At pH 7.4, mitomycin C showed greater binding affinity than streptomycin A with collagen from all three species. The reverse trend was seen at pH 3.0. Binding capacity of sepia and fish skin collagens for streptomycin A at pH 3.0 was found to be significantly greater than for mitomycin C.

Animals↗

Mitomycin C-treated Trypanosoma cruzi in vaccination of mice: induction of immunosuppression but not protection.

Attempts to immunize susceptible hosts against infection with Trypanosoma cruzi have generally not met with a high degree of success. In the present study, we used the antimetabolite mitomycin C to produce nonreplicating, attenuated culture forms of T. cruzi. Attempts to immunize highly susceptible C3H(He) mice with single or multiple inoculi of mitomycin C-treated trypanosomes 2 weeks before injection of infective blood-form trypomastigotes did not, however, lead to greater longevity in immunized mice over nonimmunized, control mice. It was determined that a single injection of 10(7) attenuated parasites induced a transient suppression of the immune response to sheep erythrocytes which was maximum on day 7, less on day 14, and undetectable by the 21st day after immunization. This immunosuppression to a heterologous antigen did not, however, appear to be the cause of the failure of the vaccination procedure to elicit protective immunity since mice immunized once with 10(7) mitomycin C-treated trypanosomes and challenged 30, 60, or 90 days later exhibited no greater longevity than control mice.

Animals↗

Deoxyribonucleic acid damage by monofunctional mitomycins and its repair in Escherichia coli.

Exposure of Escherichia coli to the antibiotic mitomycin C (MTC) at a concentration of 0.5 mug/ml caused cross-linkage between complementary strands of deoxyribonucleic acid (DNA). Derivatives of mitomycin, 7-methoxymitosene (7-MMT) and decarbamoyl mitomycin C (DCMTC), at a level as high as 20 mug/ml formed no cross-links between DNA strands. Ultraviolet light-sensitive mutants of E. coli K-12 bearing uvrA, uvrB, uvrC, or recA mutations were more sensitive to the lethal action of 7-MMT and of DCMTC than was the wild-type strain. Treatment of wild-type cells with these antibiotics resulted in the production of single-strand breaks in DNA, which were repaired upon incubation in a growth medium. Such breaks in DNA were not produced in the uvrA and the uvrB mutants. In the uvrC mutant, single-strand breaks were produced by 7-MMT or by DCMTC, but these breaks were not repaired upon incubation. These results are discussed in connection with the mechanism for removal of pyrimidine dimers in ultraviolet-irradiated bacteria.

Carbon Isotopes↗

Mitomycin C-induced synthesis of cloacin DF13 and lethality in cloacinogenic Escherichia coli cells.

Treatment of cloacinogenic cultures with increasing concentrations of mitomycin C induced an increasing synthesis of cloacin DF13 accompanied by a decreasing number of colony-forming cells. Cells grown in the presence of glucose required a 10-fold-higher concentration of mitomycin C for optimal induction of cloacin production than did cells grown with lactate. Release of the cloacin was hampered in glucose-grown cells. Experiments with various CloDF13 insertion and deletion mutants revealed that the transcription of CloDF13 deoxyribonucleic acid sequences adjacent to the cloacin structural gene was essential for mitomycin C-induced lethality.

Base Sequence↗

Enhancement of Agrobacterium tumefaciens infectivity by mitomycin C.

The ability of Agrobacterium tumefaciens to induce pinto leaf tumors may be enhanced two- to threefold after treatment with mitomycin C. The enhancement may be obtained with either lethal or nonlethal concentrations. With 10-min treatments, an optimal response was obtained with 0.005 mug of mitomycin C per ml in the absence of any change in the number of viable cells. Both the tumor induction process and the tumors induced by treated cultures appear qualitatively the same as controls. To account for these results, the antibiotic must increase the proportion of viable cells that will subsequently initiate tumors. One, or at most a few, random lesions in the bacterial chromosome seem to be the necessary requirement for this promotion. At mitomycin concentrations of 1 and 5 mug/ml, the ability of A. tumefaciens to initiate tumors is rapidly lost, indicating that a fairly intact bacterial chromosome is one of the essentials for the tumor induction process.

Chromosomes, Bacterial↗

Biochemical studies on the chi mutation of bacteriophage T4: differential inhibition of chi+ and chi DNA synthesis by mitomycin C.

Biochemical studies were carried out to determine the effect of chi mutation on T4 DNA synthesis. The rate and final extent of DNA synthesis are almost the same with T4D- and T4chi-infected cells, although the burst size of T4chi is about one-sixth that of the wild type. The DNA synthesis of T4chi-infected cells is more readily inhibited by mitomycin C than is that of T4 wild type. When mitomycin C was added during active phage growth, DNA synthesis of T4chi halted almost immediately. T4 DNA polymerases isolated from chi(+)- and chi-infected cells, however, exhibit no difference with regard to their sensitivities to mitomycin C, priming activities with alkylated or ultraviolet light-irradiated templates and other enzymatic properties.

Alkanesulfonates↗

Disruption of mouse SNM1 causes increased sensitivity to the DNA interstrand cross-linking agent mitomycin C.

DNA interstrand cross-links (ICLs) represent lethal DNA damage, because they block transcription, replication, and segregation of DNA. Because of their genotoxicity, agents inducing ICLs are often used in antitumor therapy. The repair of ICLs is complex and involves proteins belonging to nucleotide excision, recombination, and translesion DNA repair pathways in Escherichia coli, Saccharomyces cerevisiae, and mammals. We cloned and analyzed mammalian homologs of the S. cerevisiae gene SNM1 (PSO2), which is specifically involved in ICL repair. Human Snm1, a nuclear protein, was ubiquitously expressed at a very low level. We generated mouse SNM1(-/-) embryonic stem cells and showed that these cells were sensitive to mitomycin C. In contrast to S. cerevisiae snm1 mutants, they were not significantly sensitive to other ICL agents, probably due to redundancy in mammalian ICL repair and the existence of other SNM1 homologs. The sensitivity to mitomycin C was complemented by transfection of the human SNM1 cDNA and by targeting of a genomic cDNA-murine SNM1 fusion construct to the disrupted locus. We also generated mice deficient for murine SNM1. They were viable and fertile and showed no major abnormalities. However, they were sensitive to mitomycin C. The ICL sensitivity of the mammalian SNM1 mutant suggests that SNM1 function and, by implication, ICL repair are at least partially conserved between S. cerevisiae and mammals.

Amino Acid Sequence↗

Role of mitomycin C in pterygium surgery.

Mitomycin C in the form of eye drops in a concentration of 0.4 mg/ml (0.04%) was used as adjunctive treatment for primary and recurrent pterygium after surgical excision. The study was concurrent in nature and consisted of 32 pterygia in 30 patients and was done over a period of 36 months. The object was to observe the effect of mitomycin C drops on pterygium recurrence after surgical excision. Fifteen eyes of 15 patients were treated with 'bare sclera technique' for pterygium excision. Nine patients showed recurrence occurring within first 6 months of surgery. On the other hand 17 eyes of 15 patients after bare sclera pterygium excision received mitomycin 0.4 mg/ml (0.04%) eye drops four times a day for 2 weeks from first postoperative day. There was no recurrence of pterygium in this group. Follow up time for these cases ranged from 13-19 months.

Adult↗

Results of treatment with topical mitomycin C 0.02% following excision of primary pterygium.

AIMS: The effectiveness of instillation of mitomycin C eyedrops on the recurrence rate of pterygium was assessed in patients undergoing primary pterygium surgery. Any side effects were also noted. METHODS: Primary pterygia in 38 consecutive patients were surgically excised during July to December 1992. After surgery, mitomycin C 0.02% eyedrops twice daily for 5 days as well as dexamethasone 0.1% four times tapered for the next 6 weeks were instilled. Postoperative follow up ranged from 6 to 11 months. RESULTS: In one patient the pterygium recurred after 3 months (recurrence rate 2.6%). The side effects encountered were: avascularised sclera in 13 cases between 1-10 months postoperatively; ocular discomfort and lacrimation in five cases; superficial punctate keratitis during the first month in three cases; pyogenic granuloma in two cases. In one patient steroid induced increased intraocular pressure was found 4 weeks after surgery. The adverse side effects were all mild, self limiting, and easily treated. CONCLUSION: This study suggests that postoperative instillation of mitomycin C 0.02% eyedrops twice daily for 5 days following excision of primary pterygium is an effective and safe treatment to obviate pterygium recurrence.

Administration, Topical↗

Filtration procedures supplemented with mitomycin C in the management of childhood glaucoma.

AIMS: To evaluate the outcome of filtering procedures supplemented with mitomycin C in children with glaucoma. METHODS: All patients aged 17 or younger with glaucoma who underwent filtering surgery supplemented with mitomycin C at a tertiary care centre (n = 21) during a 5 year interval (1992 and 1996) were included. One eye for each patient was entered into the analysis. The postoperative intraocular pressure (IOP), use of antiglaucoma medications, clinical stability of glaucoma, complications, and visual acuity were retrospectively evaluated. Kaplan-Meier survival curves were used to estimate the probability of success. RESULTS: At the time of surgery mean age was 5.7 (SD 5.0) years. The most common diagnoses were trabeculodysgenesis (n = 6) and aphakic glaucoma (n = 8). Mean IOP before surgery was 35.7 (10.5) mm Hg. Average length of follow up was 18.6 (14.7) months. The probability of having IOP less than 21 mm Hg with no antiglaucoma medications and with clinically stable glaucoma 1 year after surgery was 76.9% in phakic eyes (n = 13) and 0% in aphakic eyes (n = 8). A phakic patient with Sturge-Weber's syndrome had choroidal effusion after surgery that resolved spontaneously. In the aphakic group one patient had retinal detachment and another developed an encapsulated bleb. Visual acuity deteriorated in one patient. CONCLUSION: A guarded filtration procedure with mitomycin C is relatively successful in phakic children with glaucoma, but unsuccessful in aphakic ones.

Adolescent↗

Trabeculectomy with mitomycin C in the treatment of post-traumatic angle recession glaucoma.

AIM: The presence of traumatic angle recession is a risk factor for failure of glaucoma filtration surgery and a previous study has suggested that antimetabolite treatment should be used in these patients. This study was undertaken to determine for the first time the mid term results of trabeculectomy with intraoperative application of mitomycin C in patients with post-traumatic angle recession glaucoma. METHODS: A retrospective analysis was made of 43 consecutive trabeculectomy procedures in 41 young black/mixed race patients followed for a mean period of 25 months (range 2-66 months). Mitomycin C 0.02% was applied between the sclera and conjunctiva for 1-5 minutes at the time of surgery. The intraocular pressure and visual acuity were measured postoperatively. The success of this technique was analysed by using a Kaplan-Meier cumulative survival curve. RESULTS: The intraocular pressure was successfully controlled at last follow up without topical treatment in 77% (33/43 eyes) and the visual acuity was the same or better in 81% (35/43 eyes). Cumulative probability of success was 85% at 1 year follow up, 81% at 2 years, and 66% at 3 years and thereafter. Hypotonous maculopathy occurred in one patient and no cases of late bleb infection were found. CONCLUSIONS: In medically uncontrolled post-traumatic angle recession glaucoma trabeculectomy with mitomycin C is an effective surgical procedure with an acceptable complication rate. Good intraocular pressure control and preservation of vision can be expected in most patients.

Adolescent↗

Ultrasound guided pericardial drainage and intrapericardial instillation of mitomycin C for malignant pericardial effusion.

BACKGROUND: Conservative treatment of malignant pericardial effusion by intrapericardial instillation of a sclerosing agent may be an alternative to surgery. METHODS: Twenty patients with malignant pericardial effusion were treated by ultrasound guided pericardiocentesis and the intrapericardial instillation of mitomycin C. RESULTS: Mitomycin C was effective in controlling the pericardial effusion in 70% of patients without causing side effects, except for pericardial constriction seven months later in one subject. CONCLUSIONS: Ultrasound guided intrapericardial instillation of mitomycin C is a suitable alternative in the management of malignant pericardial effusion.

Adult↗

Ciliary body adenoma after application of mitomycin.

PURPOSE: To describe a ciliary body tumor that was detected in a rabbit eye. METHODS: For a specific experiment, the rabbit underwent trabeculectomy with mitomycin. The eye was evaluated by electron microscopy 5 weeks following surgery. RESULTS: A ciliary body tumor was discovered in close relation to pigmented epithelial cells. The tumor cells were large with a small amount of pigment and contained prominent vesicles. CONCLUSIONS: The development of a ciliary body adenoma may be caused by the application of mitomycin. Whether the demonstrated tumor was benign or malignant could not be determined. While it could not be proven that the tumor developed related to the use of mitomycin, this possibility may be important for surgeons using this substance.

Adenoma↗

Pharmacokinetics of the antineoplastic drug mitomycin C in regional chemotherapy using the aortic stop flow technique in advanced pancreatic carcinoma.

BACKGROUND: An isolated perfusion may lead to a higher concentration of cytostatics within the target tissue, which can be associated with a high response rate and longer survival in addition to a low rate of side effects in comparison with systemic palliative chemotherapy. The aim of the present study was to investigate the pharmacokinetics of mitomycin C utilizing the aortic stop flow technique with commercially available tools in patients with advanced pancreatic carcinoma. METHODS: Seventeen patients with unresectable or metastasized pancreatic carcinoma (diagnosed by histological investigation) underwent a 20-min hypoxic perfusion of the isolated abdominal compartment with 20 mg/m2 mitomycin C (Mitomedac, medac, Hamburg, Germany) 22 times. Cytostatic concentration was determined intrainterventionally within the systemic and regional compartment. RESULTS: The mitomycin C concentration was 10 times higher within the regional compared with the systemic compartment at its maximum. The area under the curve was 4.02 times greater. Toxicity was considerable, i.e. WHO grade I/II in 8 of 17 cases, and III/IV in 9 of 17 cases. Two treatment-related deaths were documented. The objective response rate was 17.6% (3 of 17 cases; 1 complete remission, 2 partial remissions). In 3 subjects, stable disease was registered, and in 11 individuals, tumor progression. The median survival was 4.1 months. CONCLUSION: Though high concentrations of the cytostatic drug were achieved within the regional compartment, the aortic stop flow technique was associated with a high toxicity rate but no improvement of tumor response and survival in comparison with systemic chemotherapy. Despite its pharmacokinetic advantages, the aortic stop flow technique is currently not recommendable for routine use.

Adult↗

Early-onset scleral and corneal ectasias following low-dose mitomycin-C-augmented trabeculectomy in a uveitic glaucoma patient.

A case of early-onset sclerolimbal ectasia following low-dose topical mitomycin C application during uveitic glaucoma surgery is reported. Intraoperative and postoperative clinical courses were consistent with sclerolimbal ectasia. Adjunctive utilization of intraoperative low-dose 0.02% mitomycin C for the management of chronic uveitic glaucoma patients who are under concomitant systemic immunosuppressive regimen may enhance the risk of subacute postoperative sclerolimbal ectasia. Mitomycin C concentrations < 0.02%, decreased scleral exposure time, and a strict informed consent policy are strongly recommended in this subset of uveitic patients.

Adolescent↗

Capecitabine and mitomycin C is an effective combination for anthracycline- and taxane-resistant metastatic breast cancer.

Capecitabine is converted to 5-fluorouracil by thymidine phosphorylase, and mitomycin C is capable of upregulating the expression of thymidine phosphorylase suggesting a synergistic effect. Fifty-three patients (median age 62 years) with anthracycline- and taxane-resistant, metastatic breast cancer received mitomycin C 6 mg/m(2) on day 1, and capecitabine (Xeloda) 2,000 mg/m(2)/day from day 1 to day 14 with cycles repeated every 4 weeks. Overall, 77.4% had visceral metastases and 33 were pretreated with >/=3 chemotherapy lines. A median of 6 cycles were given (range 1-19) with a complete response observed in 2 patients (3.9%), partial response in 17 (33.3%) and stable disease in 19 (37.2%). Overall response rate was 37.2% (95% CI, 24.0-50.5%), with a median duration of 10.4 months. Median time to progression was 8.1 months and median survival was 17.4 months (1- and 2-year survival rates of 60 and 28%, respectively). Toxicity was mild. The most frequent grade 3/4 events were neutropenia (5.7% of patients), diarrhea (3.8%), and deep venous thrombosis (3.8%). Capecitabine plus mitomycin C may represent an effective and manageable treatment option for advanced breast cancer patients resistant to anthracyclines and taxanes. This approach provides an alternative for pretreated patients with advanced breast cancer.

Anthracyclines↗