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PubMed1992

Salvage chemotherapy with mitoxantrone and mitomycin with or without methotrexate in advanced breast cancer.

Thirty-three patients with advanced and refractory breast cancer were treated with two mitoxantrone-containing regimens (mitoxantrone plus mitomycin and mitoxantrone plus mitomycin plus methotrexate). All patients had received previous chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF); cyclophosphamide, adriamycin and fluorouracil (CAF); or CMF and CAF. Partial response occurred in five patients (15 +/- 12%), stable disease occurred in 15 patients (45 +/- 17%) and progressive disease occurred in 13 patients (40 +/- 17%). The median duration of response was 5 months. The median actuarial survival was 11 months. Toxicity was mild, even in patients who had previously received anthracyclines; generally it was mainly hematological. We thus recommend mitoxantrone-containing regimens as salvage chemotherapy in advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Effect of brief exposure to mitomycin C on cultured human nasal mucosa fibroblasts.

PURPOSE: To observe the effect of mitomycin C (MMC) on cultured human nasal mucosa fibroblasts. METHODS: Cultured human nasal mucosa fibroblasts were exposed to MMC (0.1-0.4 mg/ml) for 1 to 5 minutes. The viability of the fibroblasts was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay; DNA fragmentation (apoptosis) by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL); apoptotic percentage by flow cytometry; and morphology by light microscopy. RESULTS: A portion of the fibroblasts survived the mitomycin treatment and showed evidence of regrowth within 2 to 3 days. These cells reached confluence in 5 to 7 days. The inhibition rates by MTT assay of 0.4 mg/ml MMC for 5-minute exposures was 31.3%. Dose-response effect was noted with the lower concentrations and shorter exposure times where the inhibition rates were lower (but not significantly so). DNA fragmentation was observed in fibroblasts 24 hours after MMC exposure (0.4 mg/ml) for 5 minutes compared with normal control. The apoptotic rate of fibroblasts treated by 0.4 mg/ml MMC was significantly higher than the control (p < 0.05). CONCLUSIONS: Short MMC exposure times have a variable cytotoxic effect and inhibit proliferation of cultured nasal mucosa fibroblasts. MMC also can induce apoptosis with a 5-minute exposure time. Therefore, it is possible that MMC has a complex effect in dacryocystorhinostomy.

Alkylating Agents↗
PubMed2002

Acute scleral thinning after pterygium excision with intraoperative mitomycin C: a case report of scleral dellen after bare sclera technique and review of the literature.

PURPOSE: To describe a patient with scleral dellen after pterygium excision with intraoperative mitomycin C. METHODS: Case report and MEDLINE review of the medical literature on scleral dellen after bare sclera technique. RESULTS: A 48-year-old man had a left nasal pterygium excised by the bare sclera technique with intraoperative mitomycin C. Eight days after surgery, the patient noticed a small black spot in the bare sclera area with mild irritation. Slit-lamp examination revealed a focal area of extreme thinning, centered on the nonepithelialized bare sclera, surrounded by edematous conjunctiva. The ciliary body was visible through the thin and dry scleral lesion. After topical lubricant therapy, the scleral lesion appeared normal thickness and white in color 3 days later. Therapy was continued until the sclera epithelialized. CONCLUSIONS: Scleral dellen is an early postoperative complication of bare sclera technique owing to delayed conjunctival wound closure. Hydration of the thinned sclera will rapidly thicken it. However, medical therapy should be continued until the surrounding conjunctiva has flattened and the sclera has epithelialized. Surgical wound closure is an alternative management and may be the way to prevent scleral dellen formation after bare sclera technique. All patients after bare sclera surgery should be followed up until the conjunctival wound has healed. If delayed healing is found, frequent artificial tears, patching, or surgical intervention is necessary.

Acute Disease↗
PubMed1992

Superparamagnetic iron oxide-enhanced magnetic resonance imaging of experimental liver tumors after mitomycin C administration.

The influence of mitomycin C chemotherapy on superparamagnetic iron oxide (SPIO) uptake by the liver was studied in rats (n = 70). This commonly used antineoplastic drug induces a decrease in the phagocytic function of the macrophage-phagocytic system (MPS). The plasma clearance of SPIO measured by relaxometry followed a biexponential model. The fast component half-life increased from 2.9 minutes in controls to 4.5 minutes in mitomycin C-treated animals. The slow component half-life increased from 11.3 to 36.7 minutes. Nevertheless, the magnetic resonance imaging (MRI) diagnostic efficacy 2 hours after infusion of the superparamagnetic agent AMI 25 (n = 10) was as satisfactory in the treated group as in the untreated one. These MRI results were consistent with the relaxometric T2* liver measurements, which were identical in both groups.

Animals↗
PubMed2003

Mitomycin C for the treatment of pharyngoesophageal stricture after total laryngopharyngectomy and microvascular free tissue reconstruction.

OBJECTIVES: To assess the role of mitomycin C (MMC) in the management of pharyngoesophageal stricture after total laryngopharyngectomy and free flap reconstruction. STUDY DESIGN: Five patients since 1998 underwent evaluation and treatment for pharyngoesophageal stricture after total laryngopharyngectomy and free flap reconstruction. The method of reconstruction included four tubed radial forearm free flaps and one jejunal free flap. All patients underwent barium swallow, computed tomography, and endoscopic examination and were proven to be free of recurrent disease. METHODS: The patients were taken to the operating room. After dilation, the stenotic segment was exposed, and 1 mL of 0.4 mg/mL mitomycin-C was applied for 4 minutes using a cotton pledget. The patients were then followed clinically and with barium swallows for a minimum follow-up period of 18 months. RESULTS: All five patients experienced improved swallowing ability. The need for further dilatations was either eliminated or lessened. All patients were happy with the treatment results. No complications occurred. CONCLUSIONS: This small case series suggests that MMC is a safe and effective adjunctive treatment for pharyngoesophageal stricture after total laryngopharyngectomy and free flap reconstruction.

Adenocarcinoma↗
PubMed2003

Hypoxic pelvic and limb perfusion with melphalan and mitomycin C for recurrent limb melanoma: a pilot study.

Hypoxic pelvic and limb perfusion by means of a balloon occlusion technique was evaluated in patients with recurrent melanoma of the lower limbs who were non-responders to isolated hyperthermic limb perfusion or who were not eligible for this procedure. A pilot study was performed in 17 patients, who underwent hypoxic pelvic and limb perfusion with 50 mg/m(2) of melphalan or 50 mg/m(2) of melphalan and 25 mg/m(2) of mitomycin C. Each procedure was followed by haemofiltration. A leakage monitoring study was performed in five of the 17 patients. The response rate and time to disease progression were the primary endpoints, with overall survival as the secondary endpoint. During the procedures there were no technical, haemodynamic or vascular complications, and no deaths occurred during surgery or in the postoperative period. Significant leakage (median 40%) was measured in the five patients studied. No severe systemic or regional toxicity was observed. After one course of treatment, the objective response rate was 47% (95% confidence interval 22.5-71.5%), the median time to disease progression was 10 months (range 2-40 months), and the 3 year overall survival was 20%. Hypoxic pelvic and limb perfusion seems to be a safe and effective treatment for patients with unresectable recurrent limb melanoma who are not eligible for isolated hyperthermic limb perfusion. Due to the non-homogeneity of the study, with some patients receiving a combination of melphalan and mitomycin C and others receiving only melphalan, it is not possible to make definite conclusions with regard to efficacy. Further studies are necessary to establish whether the response rates can be improved by using different drug regimens.

Adult↗
PubMed2004

Biweekly escalated, accelerated hyperfractionated radiotherapy with concomitant single-dose mitomycin C results in a high rate of local control in advanced laryngeal and hypopharyngeal cancer.

The purpose of this study is to evaluate the efficacy of a dose-escalated, accelerated, and hyperfractionated radiotherapy schedule with a concomitant single dose of mitomycin C in the treatment of patients with advanced laryngeal or hypopharyngeal cancer. Twenty-one previously untreated patients with advanced squamous cell carcinoma (stage III, n = 6; stage IV, n = 15) were treated with a biweekly dose-escalated, accelerated, and hyperfractionated schedule up to a total dose of 74.4 Gy in 54 fractions over 5 weeks. A single dose of intravenous mitomycin C 10 mg/m2 was given on day 30. The median follow-up after treatment of surviving patients is 48 months (range, 28 to 61 months). All patients showed complete tumor control at the primary site when evaluated 2 months after chemoirradiation by laryngomicroscopy or hypopharyngoscopy and radiologic imaging (CT, MRI). Two laryngectomies were carried out after given therapy: 1 for residual cancer and 1 for suspected residual cancer. After a median follow-up of 43 months (range, 28 to 61 months), a local control rate of 70% and disease-free survival (DFS) rate of 60% were achieved in the laryngeal cancer patients; in patients with hypopharyngeal cancer, the corresponding figures were 64% (82% after salvage surgery) and 36%. The results are promising and warrant comparison with other chemoradiotherapy regimens.

Adult↗
PubMed2004

Upper eyelid retraction after glaucoma filtering surgery and topical application of mitomycin C.

PURPOSE: To describe 3 cases of upper eyelid retraction after glaucoma filtering surgery and topical application of mitomycin C and to highlight possible causes. METHODS: A report of 3 patients, identified over an 8-year interval period, who had development of upper eyelid retraction a few months after undergoing trabeculectomy with mitomycin C in the ipsilateral eye. RESULTS: Testing for Graves disease, including second-generation thyrotropin receptor antibodies (TRAb), was negative in all cases. A complete physical examination was performed by an internist: Orbital and intracranial neuroimaging studies were ordered when necessary, and all were negative. One patient underwent surgical repair of the eyelid retraction and had a satisfactory result. CONCLUSIONS: Upper eyelid retraction after filtering surgery is a rarely reported entity. Müller muscle overaction, independent of Graves disease, is a likely cause and has been pointed out as a possible factor in one previous report. Müller muscle fibrosis, euthyroid Graves disease, and mechanical hindrance to an elevated bleb are other possible factors.

Administration, Topical↗
PubMed2003

Effect of intravesical treatment of transitional cell carcinoma with bacillus Calmette-Guerin and mitomycin C on urinary survivin levels and outcome.

PURPOSE: Urine survivin is a predictive/prognostic molecular marker that detects transitional cell carcinoma (TCC) with high specificity and sensitivity. The presence of urine survivin in patients with TCC who receive intravesical instillation of bacillus Calmette-Guerin or mitomycin C may predict recurrence. MATERIALS AND METHODS: Urine from 25 subjects receiving 27 intravesical treatments of bacillus Calmette-Guerin or mitomycin C for TCC were collected prior to, during and after treatment. Urinary survivin levels were compared with outcome, as assessed by cytology and cystoscopy with or without biopsy 1 month and up to 12 months after the completion of treatment. RESULTS: Pretreatment survivin levels were higher in subjects in whom TCC recurred following treatment compared with those who achieved remission. Survivin levels increased several-fold during treatment with the highest survivin levels measured in subjects with recurrence. Median posttreatment values of survivin were zero in those who achieved remission and 1.0 ng/ml urine in subjects in whom TCC recurred. CONCLUSIONS: The presence of urinary survivin 1 month after the completion of treatment predicts TCC recurrence with 100% sensitivity and 78% specificity. Specificity to predict TCC recurrence increases to 92% after 1 year. No TCC recurred for 1 year in 12 of the 14 subjects with a posttreatment survivin level of 0.1 ng or less per ml urine. Three of the 4 subjects who were survivin positive but in remission 1 month after the completion of treatment had recurrent TCC within 1 year. Subjects who have urinary survivin after the completion of intravesical instillation have a high likelihood of TCC recurrence.

Adjuvants, Immunologic↗
PubMed2005

Vascular endothelial growth factor antisense pretreatment of bladder cancer cells significantly enhances the cytotoxicity of mitomycin C, gemcitabine and Cisplatin.

PURPOSE: Due to unsatisfactory success in the treatment of local and systemic bladder cancer and the low response rates to commonly used chemotherapy (CT) alternative and additive approaches must be found. The function of vascular endothelial growth factor (VEGF) in neo-angiogenesis and, therefore, in solid tumors makes it a promising target for a specific antitumor therapy. We investigated the possibility of sensitizing transitional bladder cancer cell lines to CT by pretreatment with VEGF antisense (AS) oligodeoxynucleotides (AS-ODNs). MATERIALS AND METHODS: The human bladder cancer cell lines EJ28 and 5637 were transiently transfected with 3 antiVEGF AS-ODNs, followed by incubation with 3 doses of mitomycin C, gemcitabine or cisplatin CT. WST-1 (a sodium salt of 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) assay (Roche, Mannheim, Germany) was performed to assess effects on cell viability. Apoptosis was examined by Annexin V staining. In all experiments a nonsense ODN served as a control. RESULTS: Each cell line responded in a dose dependent manner to all CTs. Combined treatment with VEGF AS-ODNs and CT resulted in decreased viability compared with isolated CT. VEGF857 plus CT significantly decreased the viability of the 2 cell lines compared with nonsense ODN plus CT for all 3 CT agents (p <0.007). This detected chemosensitization was based on an AS mediated increase in apoptosis. CONCLUSIONS: One of the 3 AS-ODNs tested (VEGF857) significantly sensitizes human transitional cell carcinoma cells to CT. We suggest VEGF as an additional putative target to enhance the therapeutic benefit of, for example mitomycin C and gemcitabine instillation treatment schedules.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Effects of topical application of mitomycin-C and 5-fluorouracil on myringotomy in rats.

OBJECTIVE: The effects of topical application of Mitomycin-C (MMC) and 5-fluorouracil (5-FU) for maintaining myringotomy patency were investigated in this experimental study. STUDY DESIGN: We performed simple myringotomy with a knife on 140 tympanic membranes of 70 rats. Rats were divided in two study groups and a control group. Each study group had 60 tympanic membranes, and the control group had 20. We applied Mitomycin-C (0.4 mg/ml) in Group A, 5-fluorouracil (50 mg/ml) in Group B topically, and sterile saline in the control group for 10 minutes. Examination was made with otoendoscope on days 1, 3, 5, 7, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, and 70, and patency rates were recorded. RESULTS: MMC and 5-FU Groups remained open for a mean of 46.17 days and 14.62 days, respectively. The control ears healed within 10.4 days. Fibrosis of the MMC-treated group was the same as that of 5-FU-treated groups. Fibrosis of both study groups was significantly lower than that of the control group. CONCLUSIONS: MMC is more effective than 5-FU, which is more effective than the simple myringotomy procedure in extending the patency of myringotomies in rat tympanic membranes (p < 0.05). Both medications are useful as an adjunct in preventing myringotomy closure.

Administration, Topical↗
PubMed1979

Effect of mitomycin C and 60Co gamma-irradiation on the replication of SV40 in cell lines of varying permissivity for SV40 replication.

The effects of mitomycin C and 60Co gamma-irradiation, which induce production of SV40 from SV40-transformed hamster cells, on the replication of superinfecting SV40 or virus DNA in cells varying in permissivity for SV40 replication have been examined. These agents enhance replication of SV40 in an uninducible line of SV40-transformed hamster kidney cells and in nonpermissive secondary hamster kidney cells. The same treatments do not affect SV40 replication in semipermissive hamster (BHK21) and human (HEL, HEK) cells and inhibit SV40 replication in permissive monkey (TC-7) cells. We conclude that forms of induction treatment, such as mitomycin C or 60Co gamma-irradiation, modify the expression of host cell factors which determine the level of permissivity for SV40 infection.

Animals↗
PubMed1992

Detection by ELISA of low numbers of Shiga-like toxin-producing Escherichia coli in mixed cultures after growth in the presence of mitomycin C.

Techniques currently available to detect Shiga-like toxin (SLT)-producing Escherichia coli lack sensitivity or require specialised equipment and facilities, and in some cases detect only strains belonging to serotype O157. We have used an ELISA technique, capable of detecting both SLTI and SLTII with crude P1 glycoprotein from hydatid cysts, in combination with enhancement of toxin production by culture with mitomycin C. Supernates of Tryptone Soya Broth cultures containing mitomycin C 200 ng/ml were tested for SLTII. For SLTI, cell lysates pre-treated with polymyxin B were tested. In tests with E. coli O157:H7 in mixed culture with E. coli strain C600 alone, or with E. coli C600, Proteus mirabilis and Enterococcus faecalis, SLTI could be detected when the proportion of toxigenic organisms represented 1% of the mixture, and SLTII when the proportion was 0.025%. When faecal samples with added E. coli O157:H7 were examined in this system, SLTII-producing strains were detected when they comprised less than 0.1% of the coliform population. This technique is a sensitive and specific assay for detecting low numbers of SLT-producing organisms in mixed culture such as occurs in cases of haemolytic uraemic syndrome and haemorrhagic colitis.

Bacterial Toxins↗
PubMed1989

Differential degradation of intracellular proteins in human skin fibroblasts of mitotic and mitomycin-C (MMC)-induced postmitotic differentiation states in vitro.

Rates of degradation of short- and long-lived proteins were analysed in homogeneous fibroblast cultures of mitotic or mitomycin C (MMC)-induced postmitotic states. When the highly mitotic MFII type cells--the major cell type of so called "early passage" or "young" fibroblasts--differentiate into MFIII type cells, the last mitotic fibroblast type, and further into MMC-induced postmitotic fibroblasts, the degradation of short-lived proteins increases by a factor of 1.4, resulting in significantly reduced half-lives of these proteins in the postmitotic fibroblasts. From the highly mitotic MFII to the final postmitotic PMFVI-type cells via the intermediates MFIII, PMFIV and PMFV, the half lives (t1/2) of short-lived proteins decrease by a total of 122 min in average, from 362 to 240 min. Degradation of long-lived proteins did not change significantly from cell type MFII to PMFVI. As analysed by two-dimensional (2D)-gel electrophoresis the half-lives of the mitotic and postmitotic cell-type-specific proteins except one, protein PIVa (33 kDa; Pi 5.0), range between 33.2 h and 62.9 h. Protein PIVa, the first protein specific for postmitotic cells, is initially expressed 18 h after the induction of the postmitotic state by mitomycin C (MMC) and has a half-life of approximately 66 min. This may indicate that protein PIVa could function as one possible regulatory factor controlling the postmitotic differentiation state.

Cell Differentiation↗
PubMed2004

Effect of intraurethral Mitomycin-C on healing and fibrosis in rats with experimentally induced urethral stricture.

BACKGROUND: In the pathogenesis of urethral stricture, fibrosis is associated with an excessive collagen increase. After the recognition that topical application of Mitomycin-C (MMC) inhibits fibroblast proliferation and is effective in preventing scar formation, many studies have been carried out on this subject outside the scope of urology. The aim of the present study is to observe the intraurethral impact of the employment of low doses of MMC on scar formation and fibrosis in experimental rat model. METHODS: Urethral injuries were made by internal urethrotomy knife. The study was carried out with 35 adult male Wistar albino rats. Five rats were allocated to the control group (group 1), 10 to a group that was administered 2 mg/L MMC (group 2) and 20 to a group that was administered 10 mg/L MMC (group 3). Mitomycin-C was administered to the injured urethra in the form of irrigation for 5 min. The rats were sacrificed 14 days later in order to evaluate chronic inflammation and fibrosis and their penises were histopathologically examined under light microscopy with hematoxilen eosin and trichrom stains. RESULTS: When group 2 was compared with control group, the differences in hemosiderin-laden macrophages (HLM), mononuclear cell infiltration (MCI) and fibrosis were found to be statistically significant (P < 0.01, P < 0.05, P < 0.005, respectively). When group 3 was compared with control group, the differences in HLM, MCI and fibrosis were also found to be statistically significant (P < 0.05, P < 0.05, P < 0.005, respectively). In the comparison of group 2 with group 3, no statistically significant differences were found in terms of the these parameters. CONCLUSIONS: Although MMC is toxic at high doses, the antifibrotic effect of the intraurethral low dose MMC may be useful in combination therapy for internal urethrotomy.

Animals↗
PubMed2005

Scedosporium prolificans sclerokeratitis 10 years after pterygium excision with adjunctive mitomycin C.

Scedosporium prolificans is an unusual infection, especially following pterygium surgery. A 63-year-old man who developed an uncomfortable, red right eye 10 years after pterygium surgery with adjunctive mitomycin C is described. To the best of the authors' knowledge, this is the first reported case of S. prolificans sclerokeratitis following pterygium surgery with adjunctive mitomycin C.

Amphotericin B↗
PubMedDate not supplied

Interferon alpha 2b treatment for residual ocular surface squamous neoplasia unresponsive to excision, cryotherapy and mitomycin-C.

Three patients had residual or recurrent tumour following excision of large ocular surface squamous neoplasia (OSSN) lesions, which did not resolve despite the use of adjunctive cryotherapy and topical mitomycin-C therapy. The residual tumour was treated with topical or subconjunctival injectable interferon alpha 2b. All three eyes had complete resolution of the OSSN lesions after an average of 6 weeks (range 4-8 weeks) of treatment with interferon alpha 2b. No regrowth was seen during the follow-up period of 22.7 +/- 32.3 months (range 5-60 months). No adverse reactions or complaints were reported during and following interferon use, and previous symptoms from mitomycin-C treatment resolved completely. In these patients subconjunctival or topical interferon was an effective and safe treatment for residual OSSN. Longer follow up is required to confirm the long-term efficacy in prevention of recurrences.

Aged↗
PubMedDate not supplied

Successful treatment of laryngeal stenosis in laryngo-onycho-cutaneous syndrome with topical mitomycin C.

Laryngo-onycho-cutaneous syndrome is a very rare entity found in Punjabi families. It affects the skin, nails, and larynx. Laryngeal involvement may cause lethal airway obstruction, and has in the past proved very difficult to treat. Mitomycin C is an antibiotic that acts as an alkylating agent, inhibiting DNA synthesis. It reduces fibroblast proliferation, and has previously been used to treat choanal atresia and laryngeal stenosis. We report an 18-year-old man with complete transglottic laryngeal stenosis secondary to laryngo-onycho-cutaneous syndrome. An airway was established by dissection with a bougie and sickle knife, and was initially maintained by the upper limb of a Montgomery T-tube. Laryngeal granulation tissue present on removal of the T-tube was treated with topical mitomycin C (2 mg/mL) applied for 4 minutes on two occasions with an interval of 1 month. A year later, the airway remained patent, with no granulation tissue.

Administration, Topical↗