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[Application of amnion membrane transplantation combine with mitomycin C in the treatment of pterygium].

PURPOSE: To evaluate the effect of combining amniotic membrane transplantation with mitomycin C to prevent the recurrence in primary pterygium surgery. METHOD: Forty eyes were simply excised pterygium and were applied with amniotic membrane transplantation with 0.2 mg/ml mitomycin. RESULT: Following up 6 to 18 months, the rate of recurrence is 3%. CONCLUSION: Applying amniotic membrane transplantation with mitomycin in operation can decrease pterygium recurrence, and no serious complication happens.

Adult↗

[The heat shock protein 70 antisense oligomers enhance the sensitivity of bladder cancer cell EJ to mitomycin C].

OBJECTIVE: To investigate whether the heat shock protein (HSP) 70 antisense oligomers can enhance the sensitivity of bladder cancer cell EJ to mitomycin C. METHODS: The HSP70 mRNA of EJ cells was blocked by the 10 micromol/L HSP70 antisense oligomers, while its effect on cell growth was evaluated by methyl thiazolyl tetrazolium (MTT) and colony forming ability test. RESULTS: The HSP70 expressions in HSP70 antisense treated group were lower than the corresponding sense and nonsense treated groups (P < 0.01). While, the increased sensitivity of EJ to mitomycin C was found in antisense treated group, compared with the corresponding sense and nonsense treated groups (P < 0.01). CONCLUSION: The sensitivity of bladder cancer cell EJ to mitomycin C was enhanced by the blockage of the HSP70 expression.

Cell Division↗

Evaluation of in vitro genotoxic activity of bleomycin and mitomycin C in human lymphocytes using the alkaline comet assay.

Although chemotherapy targets cancer tissue, it also damages the DNA of non-cancer cells. The aim of this study was to evaluate the in vitro genotoxic potential of therapeutic concentrations of bleomycin and mitomycin C, added alone or in combination to cultures of human peripheral lymphocytes. The levels of DNA damage and repair were assessed using the alkaline comet assay immediately after cell treatment as well as 24 and 48 hours following treatment. The results indicate that individual drugs and their combination induce a significant DNA damage to peripheral blood lymphocytes. Bleomycin alone induced the highest levels of primary DNA damage immediately after cell treatment. Although mitomycin C alone induced massive cross-linking and retarded DNA migration in resting cells, active proliferation and repair processes significantly increased DNA damage. Combined, they showed a synergetic effect, inducing complex patterns of DNA damage in peripheral blood lymphocytes and producing different types of lesions and a number of DNA alterations that directly or indirectly increased DNA migration. Our study has confirmed the sensitivity of the alkaline comet assay for assessing bleomycin and/or mitomycin C genotoxicity to human lymphocytes at concentration levels used in clinic. It has also demonstrated the utility of the alkaline comet assay as one of the primary screening methods for in vitro studies of drug-DNA interactions, especially in studying mechanisms of action of new drugs.

Adult↗

Clinical effects of intra-arterial infusion chemotherapy with cisplatin, mitomycin C, leucovorin and 5-flourouracil for unresectable advanced hepatocellular carcinoma.

BACKGROUND: Intra-arterial infusion chemotherapy (IAIC) can potentially improve survival in some patients with hepatocellular carcinoma (HCC), but the ideal regimen is not yet established. We prospectively evaluated the effects of short-course continuous infusion with the combination of cisplatin, mitomycin C, 5-fluorouracil (5-FU) and leucovorin for unresectable advanced HCC and analyzed their prognostic factors. METHODS: Patients with unresectable advanced HCC and not suitable for other therapy were enrolled. Cannulation via the left subclavian artery with the tip of catheter at the proper hepatic artery was done before initialization of IAIC routinely. The regimen consisted of the daily administration of cisplatin (10 mg/m2), mitomycin C (2 mg/m2), leucovorin (15 mg/m2), and daily infusion of 5-FU (100 mg/m2) for 5 days. Only the patients that had received at least 2 courses of IAIC were evaluated. RESULTS: Two-hundred and 11 courses of IAIC were performed, and each patient received at least 2 cycles of chemotherapy. The overall response rate was 28.3%. We observed a complete response in 5 patients (9.4%), a partial response in 10 patients (18.9%), a minimal response in 5 patients (9.4%), no change in 11 patients (20.8%) and a progressive disease in 22 patients (41.5%). The patients with response to treatment survived longer than the patients without response (24.6 +/- 14.2 months vs 8.7 +/- 5.3 months, p < 0.001). In univariate and multivariate analysis, absence of main vessel thrombosis and alpha-fetoprotein (AFP) reduction percentage > 50% following treatment showed significance in our study. All side effects subsided after conservative treatment. CONCLUSIONS: Continuous IAIC with cisplatin, mitomycin-C, leucovorin, and 5-FU is effective for patients with severe advanced HCC. Absence of main vessel thrombosis, and AFP reduction percentage > 50% following treatment were good predictors of treatment response in our study. All side effects were mild and tolerable.

Aged↗

[Determination of magnetic mitomycin C-polybutylcyanoacrylate nanoparticles in mouse plasma].

OBJECTIVE: To establish a method by high-performance liquid chromatography (HPLC) for determining the concentration of magnetic mitomycin C-polybutylcyanoacrylate nanoparticles in mouse plasma. METHODS: Chromatography was performed on a LiChroCART C18 (250 mm x 4 mm, 5 microm) column with the mobile phase consisting of acetonitrile-NaAC (15:85), the flow rate of 1.0 ml/min, and the detection wavelength of 365 nm. Sample extraction was carried out with ethylacetate. RESULTS: The linear range of mouse plasma mitomycin C concentration was 0.04-1.00 microg/ml, and the linear equation of Y=16 388X-17.17 (r=0.999 8) was derived. CONCLUSION: This method is very easy to operate and suits the need of perclinical pharmacokinetic studies of mitomycin-magnetic nanoparticles and yields accurate and precise results.

Animals↗

Effects of mitomycin C on glaucoma filtration capsules.

One of the leading causes of implantable device failure is build up of scar tissue on the device. Approaches to address this complication range from choosing device materials that prevent cell adhesion to treatment with potent antifibrotic medications such as mitomycin C. We examined the collagen matrix around aqueous shunt implants in rabbit eyes and found the filtration capsule formed around these devices is not composed of scar tissue. Rather collagen deposition is highly organized with collagen bundles oriented along stress axes. We also examined adjacent tissue deposition in mitomycin C treated animals and found decreased vascularization, condensed collagen in Tenon's capsule with more collagen bundles less well formed than those in the control eye of the same animal. The sclera was thicker under the plate than at the opposite side of the same eye. Structural and functional evaluation correlates with the clinical paradox that patients treated with mitomycin C have lower initial pressures with adjunct drug treatment but lower success rates than the control population after 18 months.

Animals↗

[Mitomycin-C-sensitive carcinoid tumor of the gallbladder: report of a case].

A case of carcinoid tumor of the gallbladder, which was sensitive to mitomycin-C is reported. A 49-year-old male was admitted to our hospital with a 2-month history of epigastralgia. He underwent right extended lobectomy of the liver, pancreaticoduodenectomy and lymph node dissection. Histology revealed a carcinoid tumor of the gallbladder with invasion of the liver and lymph node metastasis. About 2 months after the operation, right supraclavicular lymph node metastasis was detected and CT scan revealed abdominal paraaortic lymph node metastasis. The patient was given cis-platinum, but the right supraclavicular lymph node metastasis increased in size and number. After administration of mitomycin-C, the paraaortic lymph node metastasis disappeared. Carcinoid tumor obtained from the right supraclavicular lesion was inoculated into BALB/c nude mice, and sensitivity to anticancer drugs was assayed. This carcinoid tumor was sensitive to mitomycin-C but not to cisplatinum, adriamycin, or nimustine.

Animals↗

Enhanced sensitivity to mitomycin C by abating heat shock protein 70 expression in human bladder cancer cell line of BIU-87.

BACKGROUND: Bladder cancer is a relatively common tumor in the urinary system, in which mitomycin C (MMC)-based chemotherapy or combination chemotherapy has been mainly used to treat patients with advanced bladder cancer. The prognosis of patients with advanced bladder cancer is still extremely poor in spite of recent therapeutic advances. To improve the prognosis, the sensitivity of tumor cells to mitomycin C by the induction of apoptosis with the abating heat shock protein 70 (HSP70) expression in human bladder cancer cell lines of BIU-87 was investigated. METHODS: HSP70 expression was abated in BIU-87 cells by HSP mRNA antisense oligomers. MTT assay and the clone-forming test were used for evaluating the sensitivity of cells to MMC. Apoptosis was assessed using both fluorescent microscopy after staining the cells with Hoechst 33258 and DNA fragment ladder agarose electrophoresis. Thirty-two male six-week-old BALB/c nude mice, at the beginning of the experiment, were used to evaluate the effect of antisense oligomers (ASO) on the tumor formation in vivo. RESULTS: HSP70 expression in BIU-87 was effectively abated by HSP70 mRNA antisense oligomers. The percentage of apoptotic cells in ASO group was greater than in sense oligomers (SO) [P < 0.05, (18.31 +/- 2.89)% vs (1.89 +/- 0.74)%], nonsense oligomers (NO) [P < 0.05, (18.31 +/- 2.89)% vs (1.78 +/- 0.92)%] and blank groups [P < 0.05, (18.31 +/- 2.89)% vs (1.87 +/- 0.84)%], while the sensitivity of tumor cells to mitomycin C was enhanced. The in vivo tumor inhibition rate of ASO plus MMC (> 50%) was more than that of ASO or MMC group alone (all P < 0.05). CONCLUSIONS: The abating level of HSP70 expression can strengthen the sensitivity of BIU-87 to MMC. One of this effect might be related to the induction of apoptosis by abating HSP70 expression.

Apoptosis↗

Results of trabeculectomy with adjunctive intraoperative mitomycin C in Chinese patients with glaucoma.

BACKGROUND AND OBJECTIVE: To report the results of trabeculectomy with adjunctive intraoperative mitomycin C in Chinese patients with glaucoma. PATIENTS AND METHODS: The medical records of Chinese patients who received trabeculectomy with intraoperative mitomycin C from 1992 to 1998 were retrospectively reviewed. A "successful" trabeculectomy was defined as one after which the intraocular pressure (IOP) could be controlled to between 5 and 21 mm Hg, inclusive, with no more than 3 glaucoma medications. RESULTS: One hundred fourteen trabeculectomies in 105 eyes of 90 patients were retrospectively reviewed. Mean age +/- standard deviation was 48.1 +/- 21.9 years. Primary open-angle glaucoma (43.0%) and angle-closure glaucoma (27.2%) were the most common diagnoses leading to trabeculectomy. The mean follow-up +/- standard deviation was 29.6 +/- 18.6 months (range, 6 to 92 months). The overall success rate at the last follow-up was 73.7% (84 of 114 trabeculectomies). CONCLUSIONS: Trabeculectomy with mitomycin C is a safe and effective procedure for the control of IOP in Chinese patients with glaucoma.

Adolescent↗

Hypoxic stop-flow perfusion with mitomycin-C in the treatment of multifocal liver metastases. Usefulness of a vascular arterial stent to prevent iatrogenic lesions of the hepatic arterial wall.

13 patients affected by multifocal and/or large liver metastases from various solid tumors have been treated with stop-flow liver perfusion, to evaluate the safety and feasibility of hypoxic loco-regional infusion with Mitomycin C. The treatment was based on the hypoxic effect due to stop-flow, potentiating the cytotoxic activity of Mitomycin C, combined with the ischemic damage caused by the embolization of the vascular supply to the tumor. The schedule consisted in blocking arterial flow by an angiographic occlusion balloon catheter inflated in the hepatic artery, with previous placement of a vascular stent in order to prevent iatrogenic arterial lesions, and followed by the intraarterial administration of Mitomycin C; finally, arterial hepatic embolization was performed by a gelatine sponge. The study is ongoing with a median follow up of 8 months (range 2-12). Partial response was observed in 1/13 patients (8%), stable disease in 8/13 patients (61%), while progressive disease occurred in 4/13 patients (31%). Nine patients are still alive, and four patients died for hepatic progressive disease, three of them heavily pre-treated with multiple lines of chemotherapy for advanced disease. Toxicity was mild; main side effects were anaemia and thrombocytopenia(Grade 3 both in 1/15 treatments), while fever, nausea and vomiting and upper abdominal pain were short-lasting and easily manageable. No iatrogenic lesion of the hepatic arterial wall occurred. These preliminary data, although the small number of patients and the short follow up, show that the procedure is safe and feasible, with a interesting percentage of clinical responses. In addition, the placement of an arterial stent have demonstrated to protect vascular wall ensuring a regular blood flow, so allowing to perform repeated treatments in responsive patients. The good tolerability of this therapeutic modality suggests further investigation in order to determine its efficacy even in combination with systemic chemotherapy and other locoregional treatments such as termoablative procedures and/or intraarterial antiblastic perfusions in patients affected by metastatic liver disease.

Adult↗

Preliminary results of mitomycin C local application as post-treatment prevention of vaginal radiation-induced morbidity in women with cervical cancer.

PURPOSE: To determine the usefulness of local mitomycin C application in the prophylaxis of vaginal narrowing after irradiation. MATERIAL AND METHODS: 31 patients with advanced cervical cancer qualified for the study. They underwent brachytherapy with iridium-192 isotope and external beam therapy with linear accelerators. In a blind probe method 16 patients were chosen to have an aqueous solution of mitomycin C applied to the vagina. RESULTS: Radiotherapy caused a shortening of vaginal length in both groups (study and control). In the "mitomycin C group" complete vaginal occlusion was visibly less frequent as were solid fibrotic vault changes. CONCLUSIONS: This mode of morbidity prevention can potentially diminish the occurrence of local vaginal fibrosis and thus may improve patients' quality of life. Further investigations are needed to confirm these results.

Antibiotics, Antineoplastic↗

Intratumor chemoimmunotherapy with mitomycin C and components from mycobacteria in regression of line 10 tumors in guinea pigs.

Intratumor chemotherapy with the use of mitomycin C and/or immunotherapy caused regression of line 10 carcinomas in strain 2 guinea pigs and resulted in development of tumor-specific immunity. The immunotherapeutic preparation consisted of oil-in-water emulsions containing Mycobacterium cell walls or residues of cell walls termed cell wall skeletons. The latter preparations were combined with trehalose dimycolate, which was isolated by microparticulate chromatography from whole cells of mycobacteria. Reducing mitomycin C to a single intratumor injection of 50 microgram produced little necrotizing effect and a mean tumor regression rate of 17%. Intratumor immunotherapy 1 day after treatment with 50 microgram of mitomycin C resulted in regression of 90% of the treated tumors as compared to mean regression rates of 30 to 50% for immunotherapy alone. In addition, chemoimmunotherapy was more effective than either chemotherapy or immunotherapy alone in producing regression of relatively large, as well as smaller, tumors.

Animals↗

[Treatment of peritoneal carcinomatosis by intraperitoneal chemo-hyperthermia with mitomycin C. Initial experience].

Intra-peritoneal chemo-hyperthermia with mitomycin C was used to treat 9 patients with very advanced gastrointestinal cancers with peritoneal seedings. Resection of the primary tumor was possible in 3 cases. After temporary of closure of the abdominal wall, 90 to 120 minutes of intra-peritoneal chemo-hyperthermia was performed under general anaesthesia with 32 degrees C of systemic hypothermia, via 3 intra-peritoneal drains forming a closed circuit, using 10 mg/l of mitomycin C in 61 of peritoneal dialysate warmed at the inflow temperature of 46 to 49 degrees C. We observed no mortality or morbidity. There were only minor and temporary laboratory side effects and for 6 patients, no malignant cells could be found in the ascitic fluid after intra-peritoneal chemo-hyperthermia. In six patients, we conserved an improvement in the Karnofsky index 3 to 7 months after intra-peritoneal chemo-hyperthermia. These results show that intraperitoneal chemo-hyperthermia with mitomycin C is a safe and reliable treatment for peritoneal seedings in severely advanced gastrointestinal cancers and encourage us to proceed with this new therapeutic modality.

Adult↗

Comparison of vindesine plus cisplatin or vindesine plus mitomycin in the treatment of advanced non-small cell lung cancer.

Fifty-eight patients with advanced non-small cell lung cancer were randomly allocated to receive vindesine (3 mg/m2 every week) plus either cisplatin (80 mg/m2 every 3 weeks) or mitomycin (8 mg/m2 weekly X 3, then every 3 weeks). No patients achieved complete response. Among the 28 patients treated with vindesine plus cisplatin, there were 12 partial responders (42.9%); among the 30 patients treated with vindesine plus mitomycin, there were only three partial responders (10%) (P less than 0.005). The median duration of response was 11.5 weeks (range, 4-25) in the patients treated with vindesine plus cisplatin. The median survival times for patients treated with vindesine plus cisplatin and vindesine plus mitomycin were 10.1 and 10.2 months, respectively; there was no statistical difference in survival time between the two groups. Initial performance status was the strong predictor of patient survival. Toxic effects, including moderate myelosuppression, nephrotoxicity, peripheral neuropathy, and gastrointestinal symptoms, were generally manageable. The combination of vindesine and cisplatin appears to be effective against advanced non-small cell lung cancer.

Adenocarcinoma↗

Long-term follow-up study of gastric cancer patients treated with surgery and adjuvant chemotherapy with mitomycin C.

A group of 496 cases was used in a controlled trial to study the possible value of mitomycin C as an adjuvant to curative surgery for gastric cancer. Patients assigned to receive the drug were given mitomycin C, 0.8 mg/kg body weight intravenously, twice a week for 5 weeks immediately after surgery. The control group was treated with surgery alone. Sixty-six patients were excluded from the study because of non-curative surgery. There was no over-all difference in survival and cancer death rates at 5 and 10 years between treated and control groups. However, a survival rate 18.6% higher at 5 years was observed in the subset of patients who had moderately advanced lymphatic metastases, and a survival rate 26.4% higher at 5 years was observed in the subset of patients who had involved serosa. The difference in cancer death rate was 14.5 and 24.0% in each subset, respectively. These significant differences persisted at 10 years. The effect of chemotherapy seemed to result from the successful inhibition of peritoneal dissemination and local recurrence. An adverse effect was observed in patients in the early stages cancer. These results suggest that mitomycin C could be useful as an adjuvant to curative surgery for moderately advanced stages of gastric cancer.

Adult↗

Phase II trial of ftorafur with mitomycin C versus ftorafur with methyl-CCNU in untreated colorectal cancer.

In an attempt to substitute ftorafur for burdensome 5-fluorouracil (5-FU) infusions, 52 previously untreated patients were randomized to receive ftorafur with either mitomycin C or methyl-CCNU. Ftorafur was administered monthly as a 2-hour infusion daily x 5 days. Mitomycin C and methyl-CCNU were repeated every 8 weeks. A response rate of 27% (seven responses among 26 patients) was demonstrated on the mitomycin C arm compared to a response rate of 15% (four responses among 26 patients) on the methyl-CCNU arm (P = 0.25). There was no significant difference in the median survival between treatment arms. Central nervous system toxicity occurred in greater than 30% of the patients and appeared to be the limiting factor with ftorafur administration. Alternate schedules of ftorafur should be explored since there appears to be little advantage of a daily ftorafur schedule over conventional 5-FU infusions.

Adenocarcinoma↗

First-line chemotherapy of superficial bladder cancer: mitomycin vs thiotepa.

A prospective randomized study has been conducted to compare the efficacy and toxicity of thiotepa with mitomycin in patients with transitional cell carcinoma of the bladder. The 156 patients entered to date in the study were distributed by tumor grade and stage as follows: grade 1, 36 patients; grade 2, 49 patients; grade 3, 18 patients; Ta, 67 patients; T1, 33 patients; and TIS, 56 patients. All patients had tumor present in the bladder on entry to the study and after eight instillations at weekly intervals; evaluative cystoscopy and biopsy were performed four weeks later. Preliminary analysis of 156 patients indicated on overall complete response of 39 per cent for mitomycin and 27 per cent for thiotepa, which is a statistically significant difference (P = 0.02). Moderate to severe leukopenia was the most common single toxic effect with thiotepa, and a rash was the most common single toxic effect with mitomycin.

Carcinoma, Transitional Cell↗

Treatment of mitomycin-associated microangiopathic hemolytic anemia with vincristine.

A syndrome, including microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and renal insufficiency, has been recognized to occur as a complication of antineoplastic therapy with mitomycin. The clinical presentation can vary from a chronic course with mild anemia and slowly progressive renal dysfunction to a fulminant course with severe anemia, rapid deterioration of renal function, and death. The optimal treatment of the mitomycin-associated MAHA syndrome is unknown. Therapy with steroids, antiplatelet agents, and heparin sodium has failed to reverse the MAHA. Plasmapheresis has improved the MAHA in a few patients without reversing the renal failure. We treated two patients who had MAHA and renal dysfunction during chemotherapy that included mitomycin; the MAHA and hypertension both objectively improved after treatment that included vincristine sulfate.

Acute Kidney Injury↗