Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MITOMYCIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1992

Comparison of OK-432 and mitomycin C pleurodesis for malignant pleural effusion caused by lung cancer. A randomized trial.

A prospective randomized study to compare the effectiveness of pleurodesis by two new sclerosing agents: OK-432 and mitomycin C were conducted in 53 patients with malignant pleural effusion caused by lung cancer. None of the patients received concomitant systemic chemotherapy or radiation therapy during the study. After complete drainage of pleural fluid, the patients were allocated randomly to receive 10 Klinische Einheit units of OK-432 or 8 mg of mitomycin C by intrapleural injection at weekly intervals. The treatment was terminated if the pleural effusion disappeared or the patients had received four consecutive procedures. There were 26 patients who received pleurodesis with OK-432 and 27, with mitomycin C. Patient characteristics in the two treatment groups (age, sex, histologic type, performance status, and prior treatment before pleurodesis) were compatible. These results showed that pleurodesis with OK-432 achieved a higher complete response rate (73%) than that of mitomycin C (41%). The rates of objective treatment response (complete response plus partial response) were comparable in both groups (88% for OK-432 and 67% for mitomycin C). The average number of intrapleural injections needed to achieve complete response was fewer in the OK-432 group (1.9 +/- 0.9) than in mitomycin C group (2.8 +/- 0.9). There was no significant difference in the median survival of the patients who received pleurodesis with OK-432 (5.8 months) or mitomycin C (5.1 months). However, the effusion-free period in the OK-432 group was significantly longer than that in the mitomycin C group (7.0 months versus 1.5 months). Patients who underwent OK-432 pleurodesis had a higher complication rate (80%) than did those in the mitomycin C group (30%). Transient febrile reaction was the most common reaction encountered. The immunologic study in OK-432 group showed an increase in peripheral leukocyte count and decrease in the OKT4/OKT8 ratio. The mitomycin C group had a mild reduction in peripheral blood leukocyte count and no significant change in the OKT4/OKT8 ratio. It was concluded that pleurodesis with OK-432 is an effective alternative treatment for malignant effusion in patients with lung cancer.

Adenocarcinoma↗
PubMed2000

Intrascleral concentration vs depth profile of mitomycin-C after episcleral application: impact of irrigation.

Mitomycin-C has been reported to cause toxic effects on the ciliary body after episcleral application during glaucoma surgery. We investigated the intrascleral diffusion of mitomycin-C in an experimental model. The episcleral sides of scleral quadrants of 14 human donor eyes were exposed for 5 min to sponges (corneal light shield, Merocel corp., Mystic, CT, U.S.A.) soaked with 200 microg ml(-1)mitomycin-C. After the exposure one of four quadrants was not irrigated and the episcleral sides of three quadrants were irrigated with 40, 100 and 200 ml saline. A 9 mm scleral disk was punched out with a trephine and frozen on a kryotome plate 2 min after the end of mitomycin-C exposure. An 8 mm diameter scleral disk was then cut with a trephine, again frozen on a kryotome plate and then horizontally dissected with a kryotome. For analysis purposes seven cuts of 20 microm thickness were combined to one layer of 140 microm. Six layers could be reproduced and were analysed. The mitomycin-C concentrations of these layers were analysed by high-performance liquid chromatography. A concentration vs depth profile was calculated for each group, and the half-width of concentration was calculated by log-linear regression. The mitomycin-C concentration of layer 1 was 24.51 microg g(-1)(+/-7.52) without irrigation, 13.15 microg g(-1)(+/-4.38) after 40 ml irrigation, 10.29 (+/-3.53) after 100 ml irrigation and 8.4 microg g(-1)(+/-1.62) after 200 ml irrigation. In layers 1-3 the concentration of mitomycin-C was significantly reduced by irrigation (ANOVA). In the deeper intrascleral layers irrigation had no effect on the mitomycin-C concentrations. Between layers 2 and 6 the half-width of the mitomycin-C concentration was 101 microm (no-irrigation group), 141 microm (40 ml irrigation group), 153 microm (100 ml irrigation group), and 164 microm (200 ml irrigation group). Irrigation reduced the mitomycin-C concentration only down to half of the scleral thickness, leaving the deep intrascleral concentrations unchanged.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Trabeculectomy with mitomycin C: an electron microscopic and clinical study.

A prospective and randomized clinical trial was conducted to investigate the pressure-lowering effect of mitomycin C-aided trabeculectomy in the Turkish population. The scleral tissues excised during the operation were examined by light and electron microscopy. The study population consisted of 26 patients undergoing mitomycin C-aided trabeculectomy and another 26 patients subjected to trabeculectomy without mitomycin C serving as controls. The treatment groups consisted of primary open-angle and closed-angle glaucomas, congenital glaucomas, various types of secondary glaucomas and prior failed trabeculectomies. The decrease in IOP was more marked (P < 0.01) and the number of additional medications needed post-operatively was less in the mitomycin C group (P < 0.01). There were no serious complications except for transient hypotony in one mitomycin-treated eye. Transmission electron microscopic examinations showed differences between the control and mitomycin applied trabecular blocks. At the scleral dissection plane where mitomycin was applied, collagen fibrils were frayed with a loss of proteoglycan cross-links. Fibroblasts demonstrated pyknotic nuclei and loss of cell processes. In the control group, active fibroblasts and regular collagen structure were observed at this level. The middle and inner scleral layers were generally unaffected except for minor changes in some of the mitomycin-treated eyes. Our study showed mitomycin C to be safe and effective as adjunct to trabeculectomy in both primary open-angle, primary angle-closure, various secondary glaucomas and prior failed trabeculectomies. Transmission electron microscopic examinations of excised blocks showed disruption in collagen organization and cytopathic effects to fibroblasts. Mitomycin seemed to affect the proteoglycan cross-links between collagen fibrils after its application.

Adult↗
PubMed2005

Airway complications from topical mitomycin C.

OBJECTIVE: Topical application of mitomycin C appears to be a useful adjunct in reducing cicatricial scarring of the airways. Human and animal studies have demonstrated the efficacy and safety of mitomycin C topically in the treatment of airway stenosis at concentrations ranging from 0.4 mg/mL to 10 mg/mL. Although no reports of mitomycin C toxicity have been reported in the otolaryngology literature, the ophthalmologic literature has documented serious, vision-threatening complications resulting from the use of topical mitomycin C. The purpose of this study is to report complications related to mitomycin C use in the treatment of glottic and subglottic stenosis. Risk factors associated with these complications are identified. STUDY DESIGN AND SETTING: A retrospective chart review of all patients treated by the senior author for laryngotracheal stenosis with endoscopic CO(2) laser incisions/dilation and adjuvant topical mitomycin C was performed to determine the incidence of complications. Variables studied included patient age and gender, location and severity of stenosis, medical comorbidities, length of procedure, postoperative instrumentation of the airway, and mitomycin C concentration. RESULTS: Eighty-five cases of adjuvant topical mitomycin C use after CO(2) laser endoscopic treatment and dilation for upper airway stenosis were identified in a total of 44 patients. Complications that were believed to be caused by the local toxicity of mitomycin C occurred in 4 cases out of 85 (or 4.7%), manifested by accumulation of fibrinous debris at the operative site, resulting in partial airway obstruction and the need for emergent airway intervention. CONCLUSIONS: Caution should be exercised when topical mitomycin C is used in the treatment of airway stenosis.

Administration, Topical↗
PubMed2003

Intravesical bacillus Calmette-Guerin versus mitomycin C for superficial bladder cancer: a formal meta-analysis of comparative studies on recurrence and toxicity.

PURPOSE: We compare the therapeutic efficacy and toxicity of intravesical bacillus Calmette-Guerin (BCG) with mitomycin C on recurrence of stages Ta and T1 bladder carcinoma. MATERIALS AND METHODS: Combined published and unpublished data from comparative studies on BCG versus mitomycin C for superficial bladder carcinoma considering possible confounding factors were analyzed. Odds ratio (OR) and its 95% CI were used as primary effect size estimate. Toxicity data were evaluated descriptively. RESULTS: In 11 eligible clinical trials 1,421 patients were treated with BCG and 1,328 were treated with mitomycin C. Within the overall median followup time of 26 months 38.6% of the patients in the BCG group and 46.4% of those in the mitomycin C group had tumor recurrence. In 7 of 11 studies BCG was significantly superior to mitomycin C, in 3 studies no significant difference was found, while in 1 study mitomycin C was significantly superior to BCG. An overall statistically significant superiority of BCG versus mitomycin C efficacy in reducing tumor recurrence was detected (OR 0.56, 95% CI 0.38 to 0.84, p = 0.005). In the subgroup treated with BCG maintenance all 6 individual studies showed a significant superiority of BCG over mitomycin C (OR 0.43, 95% CI 0.35 to 0.53, p <0.001). In 4 of the 5 studies with reported data on toxicity BCG associated cystitis was significantly more frequent than in the mitomycin C group (53.8% versus 39.2%). The combined cystitis OR was 1.81 (95% CI 1.48 to 2.23, p <0.001). The OR for cystitis in the BCG maintenance group did not significantly differ from that in the nonmaintenance therapy group. CONCLUSIONS: The results suggest superiority of BCG over mitomycin C for prevention of tumor recurrences in the combined data and particularly in the BCG maintenance treatment subgroup, irrespective of the actual (intermediate or high) tumor risk status. The toxicity with BCG is higher but does not differ between BCG maintenance and nonmaintenance groups.

Adjuvants, Immunologic↗
PubMed2003

Apoptosis in keratocytes caused by mitomycin C.

PURPOSE: The purpose of this study was to quantify the effect of mitomycin C on rabbit keratocytes, with a view to determining its potential in modulating corneal stromal wound healing. In addition, the pathway by which this regulation occurs was investigated. METHODS: Keratocytes were isolated from New Zealand White rabbits and cultured. Hoechst staining and flow cytometric analyses with annexin V were used to identify the nature of the keratocyte response to mitomycin C. The response of cultured keratocytes to 0.005%, 0.01%, 0.02%, 0.04%, and 0.06% mitomycin C was evaluated with the lactate dehydrogenase (LDH) assay. In addition, after exposure of keratocytes to 0.01% mitomycin C, the LDH assay was performed at different times of 6, 12, and 24 hours. Keratocytes were preincubated with various concentrations of CPP32-like protease inhibitor (Z-VAD-FMK), caspase-8 inhibitor (Z-IETD-FMK), and caspase-9 inhibitor (Z-LEHD-FMK) and treated with 0.01% mitomycin C. The LDH assay was performed after 12 hours. Cytochrome c immunostain was performed after exposure to 0.01% mitomycin C. RESULTS: Hoechst staining revealed shrinkage of the cytoplasm, formation of apoptotic bodies, and nuclear fragmentation. Apoptotic changes in cells were detected by flow cytometry. LDH activities increased significantly at concentrations of 0.005% mitomycin C or greater and were time dependent until 24 hours. Treatment with a CPP32-like protease inhibitor caused a decrease in LDH activity, although the results were not statistically significant. Specific inhibitors of caspase-8 and -9 significantly reduced the LDH activity induced by mitomycin C. Cytochrome c immunostaining of keratocytes pretreated with mitomycin C showed strongly positive findings. CONCLUSIONS: Mitomycin C induced apoptosis, not necrosis, in cultured corneal keratocytes through the caspase pathway-specifically, caspase-8 and -9-related to the mitochondrial pathway.

Animals↗
PubMedDate not supplied

Suramin to enhance glaucoma filtering procedures: a clinical comparison with mitomycin.

BACKGROUND AND OBJECTIVE: Trabeculectomies performed with mitomycin are more likely to be successful, but have an increased rate of complications. We performed a novel approach to enhance the outcome of trabeculectomies using suramin, a substance that inhibits the action of growth factors. MATERIALS AND METHODS: Trabeculectomies were performed in 10 eyes of 10 patients with advanced stages of complicated glaucoma and/or poor visual prognosis in a prospective, consecutive study. For comparison, an equal number of matched controls were selected from surgical cases using mitomycin and another 20 cases without mitomycin. Pre- and post-operative data were evaluated as well as complications and the need for further surgeries. RESULTS: The follow up was 18 months for the eyes in all groups. Average IOP values decreased from 32.7 mm Hg and 29.5 mm Hg to 19.7 mm Hg and 19.3 mm Hg in the suramin and mitomycin groups. The average number of medications decreased from 2.6 and 2.5 (P <0.86, t-test) to 1.3 and 0.4 (P <0.027) in the suramin- and mitomycin-treated eyes at the last visit. Hypotony following trabeculectomy occurred in 2/10 cases in suramin-treated eyes and 5/10 cases in mitomycin-treated eyes (P <0.18). Hypotony lasting for more than three months occurred in 0/10 suramin-treated eyes and 5/10 mitomycin-treated eyes. Conjunctival dehiscence (2/10), choroidal detachment (4/10), hypotony maculopathy (1/10), and endophthalmitis (1/10) were only noted in mitomycin-treated eyes. Without mitomycin 60% of surgeries performed failed. CONCLUSIONS: In this first study using suramin to inhibit fibrosis following trabeculectomy for complicated cases of glaucoma, it appears that the use of suramin is associated with fewer cases of severe hypotony, choroidal detachment, and severe visual loss as compared to mitomycin, while the success rates seem to be similar.

Adult↗
PubMed1993

pH-dependent inactivation of DT-diaphorase by mitomycin C and porfiromycin.

Mitomycin C and porfiromycin were found to inactivate rat hepatic DT-diaphorase. Inactivation was pH dependent; little inactivation was detected at pH 5.8, but inactivation increased as the pH was raised to 7.8. Inactivation was concentration and time dependent and displayed pseudo-first-order kinetics. Inactivation was NADH dependent, indicating that reductive metabolism was necessary for inhibition. [3H]Mitomycin C was covalently bound to DT-diaphorase during inhibition, and the stoichiometry for inactivation of DT-diaphorase by mitomycin C was approximately 0.8 nmol of mitomycin C bound/nmol of enzyme. A higher molecular mass product (60 kDa) was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis of DT-diaphorase preincubated with NADH and mitomycin C at pH 7.8, suggesting that mitomycin C is capable of cross-linking DT-diaphorase. The kinetics of inhibition, requirement for NADH for inhibition, covalent binding of [3H] mitomycin C to DT-diaphorase, and approximate 1:1 stoichiometry suggest that this inactivation process may be mechanism based. Inhibition of DT-diaphorase by mitomycin C and porfiromycin is not limited to a cell-free system and could also be observed in HT-29 cells in culture at pH 7.2. Bioactivation of mitomycin C or porfiromycin by DT-diaphorase is favored at lower pH, whereas at higher pH values enzyme alkylation and inactivation of DT-diaphorase occur. These data suggest that the success of attempts to exploit the elevated DT-diaphorase content of certain human tumors for improved chemotherapeutic response using mitomycin C or porfiromycin will depend on intracellular pH.

Animals↗
PubMedDate not supplied

Effects of hypoxia and phenobarbital treatment on the metabolism of mitomycin C in experimental animals.

To evaluate the effects of anaerobic conditions and inducers for the mixed-function oxidase system on the metabolism of mitomycin C, a bioreductive alkylating agent widely used for the treatment of hepatocellular carcinoma, experiments so designed were performed in rats and mice. Metabolism of mitomycin C by microsomes from normal rat liver and diethyl-nitrosamine-induced mouse hepatocellular carcinoma tissue was assessed from the disappearance of the quinone portion of mitomycin C and by measurement of alkylating metabolites using 4-(p-nitrobenzyl)pyridine as a trapping agent. The metabolism of mitomycin C measured by the two independent methods was strikingly increased under anaerobic conditions in both intact and tumor tissues. Since involvement of cytochrome P-450 in the metabolic activation of mitomycin C was shown recently, effects of representative inducers for the mixed-function oxidase system on the metabolism of mitomycin C were also studied. Phenobarbital treatment resulted in a significant increase in the metabolism of mitomycin C in both intact and tumor tissues under anaerobic conditions. The markedly enhanced formation of active metabolites of mitomycin C under anaerobic conditions may explain on a metabolic basis, at least in part, our recent clinical observations that chemoembolizations with microcapsular forms of mitomycin C is more effective than conventional bolus administration of this agent in the treatment of hepatocellular carcinoma. Combination of anaerobic conditions and induction of the mixed-function oxidase system may be applicable to chemotherapy of hepatic malignancy.

Anaerobiosis↗
PubMed1987

Decreased transport of D-glucose and L-alanine across brush-border membrane vesicles from small intestine of rats treated with mitomycin C.

To elucidate the mechanisms underlying the dysfunctions of intestinal absorption induced by antitumor drugs, the effect of pretreatment with mitomycin C on sodium gradient-dependent D-glucose and L-alanine transports was studied in rat brush-border membrane vesicles. 24, 48, 96, or 120 h following a single intravenous injection of mitomycin C, brush-border membrane vesicles were prepared from rat small-intestines. The uptake of D-glucose and L-alanine was shown to be Na+ gradient-dependent even in the case of vesicles obtained from mitomycin C-treated rats, but uptake rates measured at 15 s and magnitude of overshooting effect in uptake of both solutes were decreased in vesicles maximally from 48 h mitomycin C-treated rats. The rate of D-glucose uptake calculated at 15 s recovered to the control level in vesicles prepared at 96 h and 120 h after mitomycin C-treatment, indicating that the effect of mitomycin C on Na+ gradient-dependent D-glucose transport would be fully reversible. Tracer exchange experiments under Na+ and D-glucose equilibrated conditions indicated that the Na+/D-glucose transporters were similarly operative in the vesicles from control and 48 h mitomycin C-treated rats. Rates of 22Na+ uptake measured at 15 s in vesicles from 48 h mitomycin C-treated rats, however, were increased. The increased permeability to Na+ might bring about a more rapid dissipation of the Na+ gradient in these vesicles and this would secondarily cause the decrease in Na+-dependent D-glucose uptake in vesicles from mitomycin C-treated rats.

Alanine↗
PubMed1986

Changes in D-glucose uptake by brush-border vesicles from small intestine of rats treated with mitomycin C.

The effect of mitomycin C pre-administration on the D-glucose transport system in the intestinal brush-border membrane of rat small intestine was examined by a rapid filtration technique. Forty-eight hours following the intravenous administration of mitomycin C, there were extensive and severe mucosal derangements. At this time point, membrane vesicles were prepared from the mitomycin-C-pretreated and control rats. Binding studies indicated that D-glucose entered into the intravesicular space of vesicles even in the case of mitomycin-C-pretreated rats. Vesicles obtained from both the mitomycin-C-pretreated and the control rats showed sodium-dependent uptake of D-glucose, but the initial uptake at 15 sec was significantly greater in control rats than in mitomycin-C-pretreated rats. Comparison of kinetic parameters of D-glucose transport indicated that Km was not significantly different between control and mitomycin-C pretreated rats. The pretreatment with mitomycin C decreased Vmax and increased the diffusional permeability to D-glucose considerably. These changes induced by mitomycin C seemed to derive not from a direct effect on mature enterocytes but from an indirect effect secondary to mitotic inhibition in the crypts.

Animals↗
PubMed1984

Mitomycin C reused: an in vitro cost-effectiveness study.

The use of mitomycin C, an effective agent in the intravesical treatment of superficial bladder cancer, is limited by its high cost. An in vitro study was done to determine whether mitomycin C could be recovered after intravesical administration and reused in the same patient. Cultured human transitional carcinoma cells from line 253-J were exposed to: medium alone; fresh mitomycin C (1 mg./ml.); mitomycin C stored for 1, 2 and 4 weeks; and mitomycin C recovered from patients after intravesical use, tested immediately and stored and tested after serial dilution after 1, 2, and 3 weeks. Results were assessed by cell counts 2 and 5 days after 2-hour exposure to the test solutions. With fresh mitomycin C and that stored up to 4 weeks, cell growth was less than 1 per cent of control (medium alone) at 2 and 5 days. Mitomycin C was also effective when recovered after intravesical use for up to 2 weeks, at which time cell growth was 9.7 and 3.1 per cent of control at 2 and 5 days, respectively. However, at 3 weeks, cell counts were 11.5 and 18.3 per cent of control at 2 and 5 days, suggesting that mitomycin C loses potency with dilution. We conclude that mitomycin C might be recovered, stored and reused for at least 2 weeks in individual patients, a practice that could result in a substantial reduction of treatment cost.

Antibiotics, Antineoplastic↗
PubMed1985

Chemopotentiation of mitomycin C cytotoxicity in vitro by platinum complexes.

The potential of cis-diamminedichloroplatinum(II) (CDDP), trans-di(2-nitroimidazole)dichloro-platinum(II) (NIPt), trans-di(2-amino-5-nitrothiazole)dichloroplatinum(II) (Plant), cis-(1,2-diamino-4-nitrobenzene)dichloroplatinum(II) (Plato), and cis-di-pyridinedichloroplatinum(II) (PyPt) to act as chemosensitizers of mitomycin C cytotoxicity toward EMT6 cells under oxygenated and hypoxic conditions has been assessed. Cells were given a 1 h treatment with the platinum complex under oxygenated or hypoxic conditions and then an additional one hour of exposure to the combination. Two concentrations of each platinum complex, 0.1 and 0.01 microM, were tested in combination with mitomycin C at 1, 0.1 and 0.01 microM. The results were analyzed via isobolograms. Under oxygenated conditions the combinations of the various platinum complexes and mitomycin C produced approximately a 2-3-fold enhancement in cell killing. Under hypoxic conditions enhancements of 5-fold, 20-fold and 60-fold were obtained with CDDP and 1, 0.1 and 0.01 microM mitomycin C, respectively. The combinations of 0.1 microM NIPT and mitomycin C under hypoxic conditions were 30-60-fold more cytotoxic than expected by additivity. With 0.01 microM NIPT a 15-23-fold enhancement of mitomycin C cytotoxicity was observed. The Plant-mitomycin C combinations produced a 5-14-fold enhancement in cell killing under hypoxic conditions. Under hypoxic conditions the combinations of 0.1 microM Plato and mitomycin C were 30-60-fold more cytotoxic than expected. At 0.01 microM Plato an 8-16-fold enhancement in cytotoxicity was observed under hypoxic conditions. PyPt and mitomycin C produced an 8-16-fold enhancement in cytotoxicity under hypoxic conditions. Overall, the platinum complexes containing radiosensitizing nitroaromatic groups were no more active in producing enhanced effects than cis-diamminedichloroplatinum(II).

Animals↗
PubMed1990

One-electron reduction of mitomycin c by rat liver: role of cytochrome P-450 and NADPH-cytochrome P-450 reductase.

1. The role of cytochrome P-450 in the one-electron reduction of mitomycin c was studied in rat hepatic microsomal systems and in reconstituted systems of purified cytochrome P-450. Formation of H2O2 from redox cycling of the reduced mitomycin c in the presence of O2 and the alkylation of p-nitrobenzylpyridine (NBP) in the absence of O2 were taken as parameters. 2. With liver microsomes from both 3-methylcholanthrene (MC)- and phenobarbital (PB)-pretreated rats, reverse type I difference spectra were observed, indicative of a weak interaction between mitomycin c and the substrate binding site of cytochrome P-450. Mitomycin c inhibited the oxidative dealkylation of aminopyrine and ethoxyresorufin in both microsomal systems. 3. Under aerobic conditions the H2O2 production in the microsomal systems was dependent on NADPH, O2 and mitomycin c, and was inhibited by the cytochrome P-450 inhibitors, metyrapone and SKF-525A. 4. Although purified NADPH-cytochrome P-450 reductase was also effective in reduction of mitomycin c and the concomitant reduction of O2, complete microsomal systems and fully reconstituted systems of cytochrome P-450b or P-450c and the reductase were much more efficient. 5. Under anaerobic conditions in the microsomal systems both reduction of mitomycin c (measured as the rate of substrate disappearance) and the reductive alkylation of NBP were dependent on cytochrome P-450. 6. The relative rate of reduction of mitomycin c by purified NADPH-cytochrome P-450 reductase was lower than that by a complete microsomal system containing both cytochrome P-450 and a similar amount of NADPH-cytochrome P-450 reductase. 7. It is concluded that although NADPH-cytochrome P-450 reductase is active in the one-electron reduction of mitomycin c, the actual metabolic locus for the reduction of this compound in liver microsomes under a relatively low O2 tension is more likely the haem site of cytochrome P-450.

Aerobiosis↗
PubMed1983

Effects of mitomycin C alone and in combination with X-rays on EMT6 mouse mammary tumors in vivo.

The effects of mitomycin C alone and in combination with radiation on the cells of EMT6 mouse mammary tumors in BALB/cKaRw mice were examined. At doses near the toxic level, approximately 98% of the tumor cells were killed by a single injection of mitomycin C. Both proliferating and quiescent cells and both hypoxic and aerobic cells were killed by the drug. Cytotoxicity with mitomycin C occurred rapidly and was apparently complete within 30 minutes after injection of the drug . No evidence was found for repair of potentially lethal mitomycin C damage or sublethal mitomycin C damage by the tumor cells. Mitomycin C and radiation in combination produced an additive cytotoxicity; neither agent was found to alter significantly the shape of the dose-response curve for the other agent. The cytotoxicity of mitomycin C and radiation in combination depended on the sequence and timing of the treatments; additive toxicities were obtained when mitomycin C was given just after, just before, or up to 24 hours before irradiation, but the combination was less effective when mitomycin C was given 2-12 hours after irradiation.

Animals↗
PubMed2000

Postoperative application of mitomycin for trabeculectomies.

BACKGROUND: Persistent hypotony is a severe complication following trabeculectomy with intraoperative application of mitomycin. OBJECTIVE: To reduce this rate of hypotony by using a lower concentration of mitomycin and applying the mitomycin only topically to the filtering bleb following surgery. METHODS: Patients were enrolled on a consecutive basis and prospectively followed up. Standard trabeculectomies were performed and mitomycin applied postoperatively on the 3 days following surgery (group 1). For comparison, data from previous studies were used for control eyes with intraoperative mitomycin application (group 2) and no mitomycin application (group 3). Preoperative and postoperative data, complications, and the need for further surgical procedures were evaluated. RESULTS: The study group (group 1) consisted of 22 cases. The mean follow-up was 13.4 and 13.5 months for groups 1 and 2, respectively. Average intraocular pressure values decreased from 33. 6 and 31.0 mm Hg (P =.32; t test) to 16.0 and 12.5 mm Hg in the 2 groups (P =.03; t test). The average number of medications decreased from 2.5 and 2.5 to 0.6 and 0.4 (P =.35; t test) in groups 1 and 2, respectively, at the last visit. Hypotony lasting for more than 3 months occurred only in eyes with intraoperative mitomycin application (14/22). Choroidal detachment (3/22) and hypotony maculopathy (2/22) also were only noted in eyes from group 2. In group 3, success rates were much lower. CONCLUSIONS: This is the first clinical study, to our knowledge, to evaluate the efficacy of this new technique of mitomycin application. From the results, it appears that the postoperative application of mitomycin following trabeculectomy is associated with a lower risk of severe and long-standing hypotony. This technique may be promising in eyes at low risk for failure.

Adolescent↗
PubMed1995

Phase I study of mitomycin C and menadione in advanced solid tumors.

A phase I study of mitomycin C with menadione (2-methyl-1,4-naphthoquinone, a vitamin K analogue which lowers intracellular pools of reduced glutathione) was designed as an approach to overcoming tumor cell resistance to alkylating agent chemotherapy. Patients with refractory solid tumors (n = 51) were treated with a 48-h continuous intravenous infusion of menadione followed by a bolus intravenous dose of mitomycin C at the completion of the menadione infusion. Initial menadione doses of 8.0 and 4.0 g/m2 over 48 h were associated with hemolysis, so subsequent dose levels of menadione ranged from 1.0 to 3.0 g/m2 with mitomycin C from 5 to 20 mg/m2. All three patients treated with menadione at 8.0 g/m2 and the single patient treated at 4.0 g/m2 with mitomycin C at 5 mg/m2 developed clinically significant hemolysis despite the presence of red blood cell glucose-6-phosphate dehydrogenase. Subsequently, a revised escalation scheme for menadione was used, and all patients tolerated menadione doses of 1-2.5 g/m2 over 48 h with mitomycin C doses up to 20 mg/m2. Since the 3.0 g/m2 dose of menadione was associated with mild hemolysis in three of four patients, the maximum tolerated dose of menadione was established at 2.5 g/m2. All of the mitomycin dose levels were tolerated without unexpected toxicities attributable to the combination. Prolonged infusions of menadione at doses which have been associated with lowering of intracellular glutathione pools in short-term exposure are limited by dose-dependent hemolysis, probably due to depletion of erythrocyte glutathione by menadione-related redox cycling. There was no detectable deleterious effect of pre-exposure to menadione on mitomycin C tolerance. We recommend a combination of menadione at 2.5 g/m2 as a continuous intravenous infusion and mitomycin C at 15 mg/m2 for further study in solid tumors, for which treatment with single-agent mitomycin C is appropriate.

Adult↗
PubMed1981

Transcatheter arterial chemoembolization of renal cell carcinoma with microencapsulated mitomycin C.

Ethylcellulose microcapsules of mitomycin C were prepared for intra-arterial use in an attempt to enhance the antineoplastic effects of mechanical arterial embolization. The potential therapeutic effects of intra-arterial mitomycin C microcapsules were considered to be a function of microembolization and prolonged drug action, that is chemoembolization. A total of 33 patients with renal cell carcinoma was subjected to transcatheter arterial chemoembolization with mitomycin C microcapsules supplemented with gelatin sponge, and 10 patients were subjected to chemoembolization with non-encapsulated mitomycin C and gelatin sponge. Comparative studies on objective tumor decrease, angiographical findings and histological effects between the 2 treated groups indicated that mitomycin C microcapsules definitely enhanced the therapeutic responses to gelatin sponge embolization. Bioassay of the peripheral blood revealed that intra-arterial mitomycin C microcapsules reduced markedly mitomycin C levels in the blood compared to non-encapsulated mitomycin C, leading to a decrease in hematological toxicity. The results may prove that chemoembolization with mitomycin C microcapsules is effective as a preoperative and palliative measure in the treatment of renal cell carcinoma.

Adenocarcinoma↗