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 1,603 records · Page 89Linked to original sources
PubMed1997

Severe visual loss after autologous blood injection for mitomycin-C-associated hypotonous maculopathy.

It has been shown that mitomycin-C increases the success rate of trabeculectomy; however, a rise in the incidence of postoperative complications has also been reported. Consequently, the use of antimetabolite is usually reserved for patients who are at high risk of surgical failure or for patients with advanced glaucoma in whom low intraocular pressure is desired. This report describes a patient who suffered severe visual loss which was a direct result of hypotonous maculopathy after trabeculectomy with mitomycin-C and various other complications from the subsequent interventions.

Adult↗
PubMed1997

MVP (mitomycin-C, vinblastine, cisplatin) salvage chemotherapy for relapsed and refractory metastatic breast cancer.

Salvage chemotherapy for relapsed and refractory metastatic breast cancer is a challenging issue for oncologists. At our institution, the combination of mitomycin-C, vinblastine and cisplatin (MVP) is used for treatment. The records of 19 consecutive patients with refractory metastatic breast cancer treated with MVP between April 1992 and October 1995 were reviewed. The regimen consisted of mitomycin-C 6 mg/m2, vinblastine 6 mg/m2 and cisplatin 60 mg/m2, repeated every 3 to 4 weeks. The median age of patients was 49 years (range, 35-71 yr). All patients had clinically measurable or evaluable disease and a Karnofsky's performance status greater than or equal to 50%. The median number of prior chemotherapy regimens was two (range, 1-4). Eighteen (94.7%) patients had previously received an anthracycline/anthracenedione-containing regimen, and seven (36.9%) had progression of disease during these therapies. Sixteen patients had two or more sites of metastasis and 17 patients had visceral disease. The median duration of follow-up was 26 months. A mean of 3.5 courses (range, 1-7) was administered. One patient was lost to follow-up after one course of treatment. Of the remaining 18 patients, two complete and five partial responses were observed, for a total response rate of 37% (range, 17-61%, 95% CI). One of the partial responders had disease progression during anthracycline treatment. Treatment-related toxicities were relatively well tolerated. There were no treatment-related deaths. The median duration of response was 3 months (range, 2-11 mo). The median overall survival was 7 months (range, 1-32 mo). Our data suggest that the MVP regimen is an effective palliative treatment for patients with refractory metastatic breast cancer.

Adult↗
PubMed1997

[Surgical revision of failed filtering bleb with mitomycin C].

The revision of a failed filtering bleb using mitomycin C was performed in 40 eyes (28 eyes with primary open angle glaucoma and 12 eyes with secondary open angle glaucoma) in which the previous trabeculectomy using 5-fluorouracil had failed to control intraocular pressure (IOP). Presurgical IOP ranged from 21 approximately 36 mm Hg (average: 24.7 mmHg) with the maximum tolerable antiglaucoma medication. The follow-up period was at least 2 years (24 approximately 60, mean: 39.8 months). Mitomycin C (0.04%, 5 ml, 5 min) was applied under the subconjunctival space. After rinsing, the wall of the scarred bleb was incised in cases with a localized bleb, or the margin of the scleral flap was incised in cases without a filtering bleb. The conjunctival wound was closed with 10-0 Nylon sutures. IOP control under 21 mmHg was achieved in 53.4% without medication and in 60.2% with or without medication at 60 months. After repeating the same procedure, IOP control was obtained in 82.2% with or without medication at 60 months. The success rate in secondary open angle glaucoma was less than in primary open angle glaucoma. Complications such as flattening of the anterior chamber requiring reformation (8%), choroidal detachment (8%), hyphema (5%), and hypotonic maculopathy (5%) were less than after trabeculectomy but conjunctival wound separation (5%) occurred little more frequently.

Adult↗
PubMed1997

A new cellular target for mitomycin C: a case for mitochondrial DNA.

Mitomycin C (MMC) is an anticancer, antibiotic that is currently used clinically against a wide variety of tumors. Nuclear DNA is regarded as the primary cellular target for mitomycin's toxicity. In this study, the effect of MMC on mitochondrial DNA was tested both in vitro and in vivo. EMT6 mouse mammary carcinoma cells were treated with MMC and conformational changes in their mitochondrial DNA were determined as a measure of mitochondrial DNA damage. A dose-dependent relationship was observed between MMC treatment dosages and mitochondrial DNA damage. Liver tissue mitochondria from Balb/c mice treated with MMC were assayed for mitochondrial integrity. Mitochondrial integrity was lowered in the MMC-treated animals. Liver tissue adenosine triphosphate (ATP) levels were also shown to be significantly decreased in these same animals. We also show that MMC can be activated by mitochondria. These studies provide strong evidence that mitochondrial DNA is a target for MMC and that this interaction has a biochemical consequence that could prove toxic.

Adenosine Triphosphate↗
PubMed1998

[Influences of trabeculectomy combined with the use of mitomycin C on corneal endothelial cells].

We used a specular microscope to evaluate the corneal endothelial cells in 119 eyes before and 2 to 3 weeks after trabeculectomy with topical mitomycin C. The endothelial cell density per square millimeter averaged 2,569 +/- 487 (mean +/- standard deviation) before surgery and 2,444 +/- 536 after surgery, showing a decrease of 4.98%. The hexagonality decreased by 1.7%, the coefficient of variation increased by 1.9, and the average cell area increased by 6.82%. There were no statistical differences as a whole in these values. Decrease in hexagonality was more frequent in eyes with prior intraocular or glaucoma surgery. Eyes treated by laser trabeculoplasty showed a decrease in endothelial cell density, an increase in coefficient of variation and an increase in hexagonality. Eyes with postoperative flat anterior chamber showed significant changes in each parameter. The findings show that trabeculectomy with topical mitomycin C does not significantly affect the corneal endothelial cells at 2 to 3 weeks after surgery.

Administration, Topical↗
PubMedDate not supplied

Effect of combination therapy with a methionine-mitomycin C conjugate and a methionine-deficient diet on tumor growth.

BACKGROUND: We investigated effects of a combination therapy of a methionine-mitomycin C conjugate (M-M conj) and methionine-free nutrition both in vitro and in vivo, compared to mitomycin C (MMC) administration alone. MATERIALS AND METHODS: The human esophageal cancer cell line, KE-3, incubated in either standard or methionine-free media, was treated with phosphate buffered saline (PBS), M-M conj in PBS, or MMC in PBS. The rate of cell survival was determined. The tumor bearing mice were maintained on either a standard or methionine-free diet (MFD) and treated with PBS, MMC, or M-M conj. RESULTS: The lowest tumor cell survival rate was found with the M-M conj plus methionine-free media at every dose tested (p < 0.05). Tumor weight was significantly lower with the M-M conj plus MFD than in any other group (p < 0.003). CONCLUSION: Methionine targets MMC to tumor during administration of MFD.

Animals↗
PubMed1998

The effect of mitomycin C on Molteno implant surgery: a 1-year randomized, masked, prospective study.

PURPOSE: The authors assess whether adjunctive mitomycin C improves Molteno tube shunt surgery in terms of intraocular pressure (IOP), visual acuity, and complication rates. PATIENTS AND METHODS: Twenty-five eyes of twenty-five consecutive patients undergoing double-plate Molteno implant surgery were randomized to receive either mitomycin C (MMC) 0.4 mg/mL for 2 minutes or a control balanced salt solution in a masked, prospective study. Intraocular pressure, visual acuity, and complications were recorded 1 week and 1, 3, 6, and 12 months after surgery. A repeated measures analysis of variance (ANOVA) model was used to test the overall effect of the drug on IOP and percent change from preoperative IOP. RESULTS: Thirteen eyes received balanced salt solution and 12 eyes received MMC. There was no difference between the groups with respect to age, preoperative IOP, log mean angle of resolution (LogMar) visual acuity, or number of preoperative medications. Except for week 1, there were no differences between the groups at any of the clinic visits with respect to IOP and percent change from baseline IOP. Analysis of the visual acuity (LogMar) showed reduction in vision for both groups. Complications were similar in each group, as were number of postoperative hypotensive agents required. CONCLUSIONS: Adjunct MMC does not demonstrate a significant difference in outcomes compared with placebo in pressure-ridged Molteno implant surgery. Results of this study are limited by a small number of patients in each group and a fixed dose of MMC.

Adult↗
PubMed1998

Three-year follow-up of trabeculectomies performed with different concentrations of mitomycin-C.

BACKGROUND AND OBJECTIVE: Mitomycin-C is effective for improving success rates of trabeculectomies. The authors sought to determine longterm success rates and complications by studying two widely used concentrations. PATIENTS AND METHODS: Trabeculectomies were performed with mitomycin-C (MMC) in concentrations of 0.5 mg/ml (group 1) and 0.2 mg/ml (group 2) in a prospective, nonrandomized fashion. Patients were observed for at least 3 years, and all follow-up data were analyzed in addition to the preoperative and postoperative conditions and complications. RESULTS: A total of 51 and 40 eyes (groups 1 and 2, respectively) were observed for 3 years. The majority of the eyes had repeat trabeculectomy. Complete surgical success was reached in 76% and 63%, respectively. The mean intraocular pressure (IOP) in the two groups decreased significantly, and the decrease was larger in the MMC 0.5 mg/ml group (P < .015). The mean visual acuity did decrease in the two groups, but this was not significant. Complications included short-term and long-term hypotony, conjunctival dehiscence, choroidal detachments, and endophthalmitis. Trabeculectomies failed both within the first 3 months (n = 4; 4%) and later (n = 11; 12%). CONCLUSION: Three-year results of trabeculectomies performed with MMC are promising. A dose-response effect of the concentration of MMC and IOP levels is present, suggesting that the higher concentration leads to lower IOP values. Despite the antimetabolic effect of MMC, trabeculectomies fail in both the short-term and the long-term.

Adolescent↗
PubMed1998

[Isolated hypoxic perfusion with mitomycin C confers no benefit for patients with advanced pancreatic carcinoma].

Since therapy options in the treatment of advanced pancreatic cancer are rare, the present study has investigated whether patients with advanced pancreatic cancer may profit from isolated hypoxic perfusion (IHP) of the abdomen with mitomycin C. None of the 17 treated patients responded to IHP with mitomycin C, and the survival time corresponded to that of untreated patients. On the basis of these results, this procedure should no longer be used as treatment for patients with advanced pancreatic cancer.

Adenocarcinoma↗
PubMedDate not supplied

Prospective randomized trial of 5-fluorouracil, doxorubicin, and mitomycin C for non-resectable pancreatic and biliary carcinoma: multicenter randomized trial.

BACKGROUND/AIMS: The efficacy of combination chemotherapy, which consists of fluorouracil, doxorubicin and mitomycin, was compared with that of palliative surgery-only in patients (control) having non-resectable pancreatic and biliary carcinomas in a multicenter randomized trial. METHODOLOGY: The patients were assigned to combination chemotherapy consisting of concomitant 5-fluorouracil 200 mg/m2, doxorubicin 15 mg/m2, and mitomycin 5 mg/m2 by intravenous administration. This combination chemotherapy was given concurrently as the initial dose within 1 week after palliative operation, and this regimen was repeated for at least 2 whole courses at 4-week intervals before the next course of therapy. Forty-two cases of this combination chemotherapy group and 41 of the control group were completely eligible for analysis. RESULTS: Regarding the overall 50% inhibition of tumor progression and that of gallbladder carcinoma, there were significantly better outcomes in the modified FAM therapy group. In this group, tumor reduction was achieved in 1 complete response (CR) and 2 partial response (PR) patients. With respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy, there was no difference between the groups. The most frequent adverse reactions were gastrointestinal manifestations such as anorexia, nausea, vomiting, and diarrhea; also noted was alopecia. CONCLUSIONS: Since this combination chemotherapy inhibited the tumor progression for significantly longer duration and, to a lesser extent, reduced the tumor size in non-resectable gallbladder carcinomas compared to a non-administrated chemotherapy group, this study will function as the basis for pursuing a more effective chemotherapy.

Adult↗
PubMed1985

Quantitative aspects of the degradation of mitomycin C in alkaline solution.

The alkaline hydrolysis of mitomycin C has been studied over a wide range of pH/H_(7-15). A stability-indicating high-performance liquid chromatographic (HPLC) method was used to separate the degradation products from the parent drug. The quantitative effects of temperature and buffers on the degradation of mitomycin C in alkali have been determined. A profile of log k(obs) against pH/H_ was constructed after corrections had been made for buffer effects and after extrapolation to 25 degrees C by application of the Arrhenius equation.

Journal Article↗
PubMed1999

A Novel Class of CC-1065 and Duocarmycin Analogues Subject to Mitomycin-Related Reductive Activation.

A new class of DNA alkylating agents is described that incorporate the quinone of the mitomycins, which is thought to impart tumor cell selectivity as a result of preferential reduction and activation in hypoxic tumors, into the AT-selective binding framework of the duocarmycins capable of mitomycin-like reductive activation and duocarmycin-like spirocyclization and subsequent DNA alkylation. Consistent with this design, the quinone prodrugs fail to alkylate DNA unless reductively activated and then do so with an adenine N3 alkylation sequence selectivity identical to that of the duocarmycins. Additionally, the agents exhibit a selectivity toward DT-Diaphorase (NQO1)-containing versus DT-Diaphorase-deficient (resistant) tumor cell lines, and they were shown to be effective substrates for reduction by recombinant human DT-Diaphorase. As such, the agents constitute effective duocarmycin and CC-1065 analogues subject to reductive activation. In addition, the solvolysis pH rate dependence of a series of reactive spirocyclopropanes revealed a unique and inverted order of reactivity at pH 7 versus pH 3. This behavior and the structural features responsible for it are consistent with an acid-catalyzed reaction at pH 3, but a direct uncatalyzed S(N)2 reaction at pH 7 that is not subject to acid catalysis.

Journal Article↗
PubMed2000

Phase II study of vincristine, bleomycin, mitomycin C and cisplatin (VBMP) in disseminated squamous cell carcinoma of the uterine cervix.

The objective of this study was to study the antitumor activity of the vincristine, bleomycin, mitomycin C and cisplatin (VBMP) scheme in patients with disseminated squamous cell carcinoma of the uterine cervix and to document its toxicity. VBMP consisted of vincristine 1.4 mg/m2 (max. 2 mg) i.v. day 1, bleomycin 15 mg/day by continuous i.v. infusion on day 1 + 2, mitomycin C 6 mg/m2 i.v. day 3 and cisplatin 50 mg/m2 i.v. day 4, and was given every 4 weeks. Bleomycin was withdrawn from the schedule after a cumulative dose of 300 mg (210 mg in patients over 60). Thereafter VMP continued (V + M day 1, P day 2) with the same interval. A median number of 4.5 (range 2-13) treatment cycles was given to 50 fully evaluable patients, 26 with only distant metastases (group A) and 24 with pelvic disease also (23 previously irradiated) (group B). All patients were < 70 years old, had a Karnofsky index >/=60, and measurable metastatic lesions outside previously irradiated areas. They all had normal organ functions and gave informed consent. Response in group A was 54% (31% complete), in group B 25% (all partial), 40% in all. Median time to progression in group A was 20 weeks and in group B 15 weeks; median survival was 42 weeks in group A, 32 weeks in group B, 37 weeks for all patients. Hematologic toxicity was cumulative and the majority of patients needed blood transfusions. Nonhematologic toxicity was acceptable, but in one patient pulmonary toxicity might have contributed to death. Although it is active, it is unclear whether this regimen is superior to cisplatin alone.

Journal Article↗
PubMed2000

The role of reductive enzymes in cancer cell resistance to mitomycin C.

Mitomycin C (MMC) is bioreductively activated to DNA binding species via complex chemical pathways involving a common hydroquinone intermediate. A recent publication by Belcourt et al. (1999) has revealed that the bacterial mitomycin C resistance protein (MCRA) acts as a unique hydroquinone oxidase converting this reactive intermediate back to the parent drug in the presence of molecular oxygen, preventing the formation of cytotoxic interstrand DNA crosslinks. It was argued that a mechanism analogous to MCRA may be responsible for the often observed phenomenon of aerobic drug resistance that develops in vitro to MMC in human cancer cell lines. Altered expression of activating reductase enzymes, which usually accompanies aerobic drug resistance, was claimed to be of lesser importance. Therefore, the role of reductases in MMC drug resistance has been reviewed. While it is clear from numerous studies that lowered reductase expression can in certain situations produce drug resistance, simple correlations between a specific enzyme and chemosensitivity generally do not hold due to the complex functional and regulatory interplay that exists among the different activating enzymes and detoxification systems. Copyright 2000 Harcourt Publishers Ltd.

Journal Article↗
PubMed1999

Use of mitomycin C and 5-fluorouracil in external dacryocystorhinostomy.

PURPOSE. To evaluate the effects of antiproliferative agents on the fibrous tissue responsible for the failure of external dacryocystorhinostomy at the site of surgical rhinostomy. METHODS. The study group consisted of 60 cases. Patients with primary acquired idiopathic nasolacrimal duct obstruction were divided into three groups according to the agent used. Each group consisted of 20 patients. Mitomycin C was applied to the first group (0.5 mg/ml to 10, 1 mg/ml to 10 cases) and 5-flourouracil to the second group (2.5 mg/ml to 10, 5 mg/ml to 10 cases). The third group consisted of 20 control cases. The mean follow-up period was 15.3 +/- 2.60 (12-18) months. The tissues obtained during the revision of the cases with failure were evaluated by light and electron microscopic examination. RESULTS. External dacryocystorhinostomy failed in four cases. Of these, one was in the first group (0.5 mg/ml mitomycin C), one in the second group (2.5 mg/ml 5-flourouracil), and two were in the control group. Light microscopic examination of the tissues revealed an increase in fibroblastic activity in the control group whereas hypo- and acellular areas were found to be dominant in the groups given antifibroblastic agents. The control group revealed more active fibroblasts with cytoplasms containing numerous organelles in electron microscopic examination. Electron microscopic examination of the cases given antifibroblastic agents revealed fibroblastic cells with nuclear fragmentation, necrosis or pyknosis, while some others had scanty cytoplasms poor in organelles. CONCLUSION. We can conclude that intraoperative antiproliferative agents improve the success rate of external dacryocystorhinostomy.

Journal Article↗
PubMed2003

Randomized, controlled, multicenter phase III trial of standard-dose fluorouracil-epirubicin-cyclophosphamide (FEC), compared with time-intensive FEC (FEC-G) and mitoxantrone-methotrexate-mitomycin C (MMM-G) in metastatic breast carcinoma.

The purpose of this multicenter phase III trial was to assess the impact of a time-intensification of FEC (fluorouracil, epirubicin, cyclophosphamide) and MMM (mitoxantrone, methotrexate, mitomycin C) regimens, supported by lenograstim (G-CSF) on the objective response rate, time to progression and survival of patients with chemotherapy-naive metastatic breast cancer (mbc). Women with mbc were randomized to receive as first-line chemotherapy either standard-dose FEC (all doses in mg/m2): arm A (500, 75, 500 every 21 days), or time-intensified FEC-G: arm B (500, 75, 500 every 14 days), or time-intensified MMM-G: arm C (mitoxantrone 10, methotrexate 35 every 14 days and mitomycin C 10 every 28 days), both with support of lenograstim (G-CSF 150 microg/m2/day s.c. for 10 days). All study treatments were administered for six cycles. Eligible female patients were in the 31-70 year range with histologically proven mbc, and measurable or evaluable disease. An intent-to-treat analysis was performed. The overall response rate (CR + PR, intent-to-treat analysis) was significantly improved in the time-intensified FEC-G regimen (69%) in comparison with standard-dose FEC (41%), p=0.002. Time-intensified MMM-G (51%) did not lead to a significant improvement in the response rate. The percentage of complete responses was significantly higher in the FEC-G arm as compared to standard-dose FEC (17% vs. 4.7%; p=0.002). The median duration was longer in the intensified-dose arms without, however, achieving a statistically significant improvement. The median time to progression (TTP), and the median survival time did not differ between the three treatment arms. Grade 3-4 leukopenia was significantly higher (p<0.001) in the standard FEC regimen-treated patients. Thrombocytopenia was significantly higher (p<0.001) in both intensified regimens. Alopecia and mucositis were significantly more frequent in both anthracycline-containing regimens (p=0.003). Other hematological and non hematological toxicities were similar in the 3 treatment arms. The increase of dose-intensity of both FEC and MMM regimens improved activity, but not efficacy as compared to standard FEC regimen in our group of chemotherapy-naive, metastatic breast cancer patients.

Adult↗
PubMedDate not supplied

Concurrent 5-fluorouracil, mitomycin C and radiation, with or without brachytherapy, in recurrent endometrial cancer: a scoring system to predict clinical response and outcome.

AIMS AND BACKGROUND: This prospective, phase II study aimed to test the efficacy of concurrent 5-fluorouracil, mitomycin C and radiation, with or without brachytherapy, on the clinical outcome of a series of recurrent endometrial cancer patients and to determine the prognostic impact of a subset of factors. METHODS: Thirty patients with locally recurrent, nonmetastatic endometrial cancer received external beam radiation (4-week split course: 23.4 + 23.4 Gy) plus two courses of concomitant chemotherapy (5-fluorouracil, 96-h continous infusion, days 1-4; 1 g/m2/day; mitomycin C, 10 mg/m2, bolus iv, day 1). Nineteen patients (63.3%) underwent endocavitary, low-dose brachytherapy boost (20-25 Gy); eight patients (26.7%) received external beam radiation boost (14-20 Gy). RESULTS: Eleven complete responses (36.7%), 11 partial responses (36.7%), 6 disease stabilizations (20.0%) and 2 progressions (6.6%) were observed. After a median follow-up of 27 months (range, 1-108), overall actuarial 3-year survival, progression-free survival and local progression-free survival were 46.8%, 35.2% and 41.2%, respectively. Two patients (6.7%) experienced hematological grade 3 toxicity. Two patients (6.7%) had grade 3 intestinal toxicity. Severe late toxicity was infrequent, only 3 patients showing severe vaginal stenosis (10.0%). A clinical score of 0 to 1 was assigned to each patient on the basis of the absence (score = 0) or presence (score = 1) of any of the following prognostic factors: time between surgery and recurrence shorter than 12 months, pelvic wall site of recurrence, positive lymph nodes, hemoglobin < 11 g/dL. With this device, it was clear that patients with a low score had a significantly better outcome (clinical remission: 77.2% of patients with a score < 2 vs 25.0% of patients with a score > or = 2, P = 0.009), better local control of the disease (50.2% vs. 0 at 3 years, P = 0.014,) and better overall survival (65.8% vs 0 at 3 years, P = 0.003). CONCLUSIONS: Our data suggest that this combined modality therapy was relatively well tolerated and resulted in reasonable local control and survival. The scoring system proved to be helpful in identifying patients with the best chance of benefiting from the treatment.

Adult↗
PubMed1990

Effects of mithramycin, mitomycin, daunorubicin, and bleomycin on human subconjunctival fibroblast attachment and proliferation.

Scar formation and fibrosis are the most common causes of ultimate glaucoma filtration surgery failure. The authors used Coulter counter, hexosaminidase, and 3H-thymidine assays to evaluate the effects of mithramycin, mitomycin, daunorubicin, and bleomycin on human subconjunctival fibroblast growth in tissue culture. Fifty percent inhibitory doses (ID50) for each drug on different days of incubation with fibroblasts were calculated with these three assays. Among these four drugs only daunorubicin exerted a significant effect on cellular attachment, showing cytotoxicity at 4 x 10(-6) M. However, all drugs had antiproliferative effects. Daunorubicin was the most potent drug in the concentration range studied. Mithramycin had a narrow therapeutic range in tissue culture. Cellular antiproliferative responses to mitomycin and bleomycin were more gradual. These drugs have potential applications in the prevention of glaucoma filtration surgery failure.

Antibiotics, Antineoplastic↗