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PubMed2004

Population pharmacokinetics and pharmacodynamics of mitomycin during intraoperative hyperthermic intraperitoneal chemotherapy.

BACKGROUND: During recent years, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin has been used for various malignancies. OBJECTIVE: To characterise the population pharmacokinetics and pharmacodynamics of mitomycin during HIPEC. METHODS: Forty-seven patients received mitomycin 35 mg/m2 intraperitoneally as a perfusion over 90 minutes. Mitomycin concentrations were determined in both the peritoneal perfusate and plasma. The observed concentration-time profiles were used to develop a population pharmacokinetic model using nonlinear mixed-effect modelling (NONMEM). The area under the plasma concentration-time curve (AUC) was related to the haematological toxicity. RESULTS: Concentration-time profiles of mitomycin in perfusate and plasma were adequately described with one- and two-compartment models, respectively. The average volume of distribution of the perfusate compartment (V1) and rate constant from the perfusate to the systemic circulation (k12) were 4.5 +/- 1.1L and 0.014 +/- 0.003 min(-1), respectively (mean +/- SD, n = 47). The average volume of distribution of the central plasma compartment (V2), clearance from the central compartment (CL) and volume of distribution of the peripheral plasma compartment (V3) were 28 +/- 16L, 0.55 +/- 0.18 L/min and 36 +/- 8L, respectively. The relationship between the AUC in plasma and degree of leucopenia was described with a sigmoidal maximum-effect (Emax) model. CONCLUSIONS: The pharmacokinetics of mitomycin during HIPEC could be fitted successfully to a multicompartment model. Relationships between plasma exposure and haematological toxicity were quantified. The developed pharmacokinetic-pharmacodynamic model can be used to simulate different dosage schemes in order to optimise mitomycin administration during HIPEC.

Antibiotics, Antineoplastic↗
PubMed2004

Mitomycin C in preventing spinal epidural fibrosis in a laminectomy model in rats.

OBJECT: Extensive epidural fibrosis after lumbar surgery may be the underlying cause in most cases of failed-back surgery syndrome. Various materials have been used to prevent epidural fibrosis, but only moderate success has been shown. Mitomycin C, an alkylosing antibiotic substance isolated from Streptomyces caespitosus, potentially supresses fibroblast proliferation after surgery. In this study, the authors investigated the effect of mitomycin C by local application on spinal epidural fibrosis in a rat laminectomy model. METHODS: Five Wistar rats underwent laminectomy at cervical, thoracic, and lumbar levels. Based on data obtained from ophthalmological studies, mitomycin C was applied to the laminectomy sites in various concentrations (0.01, 0.05, and 0.1 mg/ml). One laminectomy site in each rat was left untreated and thus served as a control. Evoked potentials were measured pre- and postoperatively, and all rats underwent clinical evaluation. Mobility status and evidence of neurological deficit were recorded. Twelve weeks later, the rats were killed, and the spinal column, including surrounding muscle tissue, was removed en bloc, decalcified, and fixed in formaldehyde. Epidural fibrosis was evaluated histologically. In all mitomycin C-treated laminectomy sites, epidural scarring was significantly reduced compared with control sites. Remarkably, dural adhesions were absent in laminectomy defects treated with mitomycin C concentrations of 0.05 and 0.1 mg/ml. Moderate to marked epidural fibrosis with adhesion to the dura mater was noted at sites receiving 0.01 mg/ml of mitomycin C. All control sites showed dense epidural fibrosis with marked dura adherence. CONCLUSIONS: In this experimental model, mitomycin C applied locally at a concentration of 0.1 mg/ml effectively reduced epidural fibrosis, completely avoided dural adherence, and induced no side effects.

Alkylating Agents↗
PubMed2002

Mitomycin as a modulator of irinotecan anticancer activity.

Irinotecan and mitomycin (Mutamycin) possess significant single-agent activity against several tumor types, and mitomycin activates topoisomerase I, the cellular target of irinotecan. We conducted a phase I dose-escalation study of irinotecan and mitomycin in 37 evaluable patients with solid tumors. Antitumor responses included 2 complete responses, 5 partial responses, 10 minor responses, and a CA 19-9 tumor marker response. Responders included 14 patients previously treated with chemotherapy for metastatic disease. No pharmacokinetic interaction between mitomycin and irinotecan was apparent when these agents were given 24 hours apart. Responders (complete and partial responses) demonstrated the largest topoisomerase I induction 24 hours following mitomycin infusion. In addition, since maximum topoisomerase I up-regulation was reached 24 hours after administration of mitomycin, a delay in the administration of irinotecan after mitomycin appeared justified. Based on these encouraging phase I data, phase II clinical trials in breast and esophageal/gastroesophageal junction adenocarcinomas at the recommended doses and schedule are under way.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

[Adriamycin and mitomycin dose-dependently downregulate X-kinked inhibitor of apoptosis protein in human bladder cancer cells].

OBJECTIVE: To investigate the efficacy of inducing apoptosis in human bladder cancer cells by adriamycin and mitomycin and relevant mechanism. METHODS: Human bladder cancer cells of the lines RT4, MGH-U1, FJ, and T24 were cultured. Adriamycin of the concentrations of 0.1, 1, and 10 microg/ml, and mitomycin of the concentrations of 0.01, 0.1, and 1 microg/ml were added into the culture fluid respectively. CCK-8 colorimetric assay was used to detect the survival rates of the cells so as to select the cell line sensitive and tolerable to the drugs. Flow cytometry was used to detect the cell apoptosis. Western blotting was used to detect the levels of X-kinked inhibitor of apoptosis protein (XIAP) and the cleavage of caspase-3 precursor. RESULTS: It was found that RT4 cells were the most sensitive and the T24 cells were the most tolerable to adriamycin and mitomycin. Treated with adriamycin of the concentrations of 0.1, 1, and 10 microg/ml for 24 hours, the apoptotic rates of the RT4 cells were 15.3% +/- 4.3%, 29.3% +/- 6.4%, and 45.0% +/- 5.5% respectively; and the apoptotic rates of the T24 cells were 7.3% +/- 3.1%, 12.5% +/- 4.3%, and 18.2% +/- 6.3% respectively, all significantly lower than those of the RT4 cells (P < 0.05 or P < 0.01). Treated with mitomycin of the concentrations of 0.01, 0.1, and 1 microg/ml for 24 hours, the apoptotic rates of the RT4 cells were 12.7% +/- 2.9%, 31.3% +/- 4.4%, and 48.9% +/- 5.8% respectively, and the apoptotic rates of the RT4 cells were 7.2% +/- 3.3%, 15.5% +/- 5.2%, and 21.2% +/- 4.4% respectively, all significantly lower than those of the RT4 cells (all P < 0.05). The XIAP expression was not significantly different in these 4 cell lines before the adriamycin and mitomycin treatment. After the treatment of adriamycin and mitomycin, the expression of XIAP was down-regulated dose-dependently, however, being weaker in the T24 cells than in the RT4 cells; and caspase-3 precursor cleavage was enhanced, however, being weaker in the T24 cells too. CONCLUSION: Adriamycin and mitomycin dose-dependently kill the human bladder cancer cells. Such cytotoxic effect may be realized through inducing the cell apoptosis which is associated with the down-regulation of XIAP and cleavage of caspase-3 precursor.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Re-evaluation of tumor-specific cytotoxicity of mitomycin C, bleomycin and peplomycin.

Three antitumor antibiotics, mitomycin C, bleomycin sulfate and peplomycin sulfate, were compared for their tumor-specific cytotoxicity, using human oral squamous cell lines (HSC-2, HSC-3, HSC-4, Ca9-22 and NA), human promyelocytic leukemic cell line HL-60 and human normal oral cell types (gingival fibroblast HGF, pulp cell HPC and periodontal ligament fibroblast HPLF). Among these three compounds, mitomycin C showed the highest tumor-specificity, due to its higher cytotoxic activity against human oral tumor cell lines than bleomycin and peplomycin. However, there was considerable variation of drug sensitivity among the six tumor cell lines. Mitomycin C induced internucleosomal DNA fragmentation and caspase-3, -8 and -9 activation in HL-60 cells only after 24 h. On the other hand, mitomycin C induced no clear-cut DNA fragmentation in HCS-2 cells, although it activated caspase-3, -8 and -9 to a slightly higher extent. Western blot analysis demonstrated that mitomycin C did not induce any apparent change in the intracellular concentration of anti-apoptotic protein (Bcl-2) and pro-apoptotic proteins (Bax, Bad). Electron microscopy of mitomycin C-treated HL-60 cells showed intact mitochondria (as regards to integrity and size) and cell surface microvilli, without production of an apoptotic body or autophagosome, at an early stage after treatment. The present study suggests the incomplete induction of apoptosis or the induction of another type of cell death by mitomycin C treatment.

Antibiotics, Antineoplastic↗
PubMed1978

The effect of mitomycin C on platelet aggregation and adenosine 3',5'-monophosphate metabolism.

The effect of Mitomycin C on aggregation, adenosine 3',5'-monophosphate (cyclic AMP) metabolism and reactions induced by thrombin was studied in rabbit platelets. Mitomycin C inhibited the platelet aggregation induced by adenosine diphosphate or thrombin. The level of radioactive cyclic AMP derived from 8-14C adenine or 8-14C adenosine increased after incubating intact platelets with Mitomycin C. Formation of radioactive adenosine triphosphate also increased though mitochondrial oxidation was not stimulated. Similar effect was observed also in rabbit liver. Mitomycin C failed to stimulate platelet adenyl cyclase but inhibited cyclic AMP phosphodiesterase in the absence of theophylline. In the platelets preincubated with Mitomycin C, thrombin-induced inhibition of adenyl cyclase, stimulation of membrane-bound cyclic AMP phosphodiesterase, and release of 250,000 dalton protein from platelet membranes were prevented. These results suggest that Mitomycin C will affect cellular membrane structure and function, and this extranuclear effect of Mitomycin C will lead to inhibition of aggregation in blood platelets.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Long-term follow-up study of mitomycin eye drops as adjunctive treatment of pterygia and its comparison with conjunctival autograft transplantation.

We observed 48 patients for 7-21 months (mean, 18 months) after pterygium excision and 2 weeks of placebo or mitomycin topical therapy to evaluate whether or not the short-term efficacy of mitomycin in preventing pterygium recurrence would be reflected in long-lasting efficacy as well. Placebo-treated pterygia showed a 73% recurrence rate. One of 58 (1.7%) mitomycin-treated pterygia recurred (p less than 0.05). We also performed a pilot study comparing pterygia treated with excision followed by 0.4 mg/ml of mitomycin to pterygia treated with excision coupled with conjunctival autograft transplantation to estimate the number of patients required for a randomized clinical trial comparing these two treatment modalities and thereby to decide whether or not such a study would be justified. Thirteen primary and two recurrent pterygia were treated with mitomycin, while 14 primary and one recurrent pterygia were treated with conjunctival autograft transplantation. With mean follow-up times of 4 and 6 months, respectively, no recurrences were noted in the mitomycin-treated group, while the conjunctival autograft transplantation group had one recurrence (6.6%). We estimate that 400 patients would be required for a properly designed clinical trial comparing these two effective therapies for prevention of recurrent pterygia. We conclude that such a study is unjustified, and further conclude that the vastly less expensive, simple therapy of mitomycin eye drops is the more appropriate treatment.

Administration, Topical↗
PubMed1979

[Action of mitomycin C on the variability of Actinomyces hygroscopicus in forming a proteolytic complex of hygrolytin enzymes and the antibiotic, hygromycin B].

The lethal and mutagenic effect of mitomycin C in doses of 10 and 15 micrograms/ml on the spores and 24-hour culture of Act. hygroscopicus, strain O878 producing hygrolytin, a proteolytic enzyme and hygromycin B, an antibiotic was studied. It was found that mitomycin C had a high lethal effect on the organism. The lethal effect of the antibiotic depended on the stage of the culture development, mitomycin C dose and exposure time. The 24-hour culture was most sensitive to the effect of mitomycin in a dose of 50 micrograms/ml. Exposure to mitomycin increased the actinomycete variation with respect to the colony morphology and induction of new morphological mutations. Exposure of strain O878 to mitomycin C significantly increased the culture variation with respect to the quantitative features of production of the hygrolytin proteolytic enzyme complex and hygromycin B. The character of the strain induced variation with respect to the features studied was different which indicated the absence of correlation between them. The use of mitomycin C proved to be promising in selection of Act. hygroscopicus with a purpose of increasing the culture proteolytic and antibiotic activity.

Anti-Bacterial Agents↗
PubMed1981

Enhancement by hyperthermia of the in vitro cytotoxicity of mitomycin C toward hypoxic tumor cells.

Mitomycin C and hyperthermia are both toxic to chronically hypoxic EMT6 tumor cells. Combinations of this drug and heat were tested in vitro in normally aerated and chronically hypoxic EMT6 mouse mammary tumor cells to establish whether greater than additive cytotoxicity could be achieved by combined treatment. Cell survival was measured at four concentrations of mitomycin C (0.01, 0.1, 1.0, and 10 microM) at 37 degrees or at elevated temperatures (41, 42, and 43 degrees) for durations of 1, 2, 3, and 6 hr. At 42 degrees, exposure to mitomycin C for 3 and 6 hr produced a 2- to 3-fold increase in hypoxic tumor cell kill at all drug concentrations over that expected for strict additivity. A 15-fold enhancement in the kill of hypoxic tumor cells was obtained at 1.0 and 10 microM mitomycin C at 43 degrees for 6 hr of exposure. Under most conditions, additivity was observed for the antibiotic and heat in oxygenated cells, except at 43 degrees with 0.01 and 0.1 microM mitomycin C following 3 and 6 hr of treatment, conditions under which a 5- to 10-fold potentiation of tumor cell kill was obtained. The rate of formation of reactive metabolites from mitomycin C under anaerobic conditions in EMT6 cell-free preparations was measured. A 30 to 50% increase in alkylating activity was observed at elevated temperatures, suggesting that the enhanced cytotoxicity of mitomycin C with heat toward hypoxic cells may, in part, be due to an increase in activation of the drug.

Aerobiosis↗
PubMed1993

Reductive activation of mitomycin C by NADH:cytochrome b5 reductase.

Mitomycin C requires bioreduction in order to exert its cytotoxic action. Activation of mitomycin C to an electrophile was equally supported by NADPH and NADH in EMT6 tumor cell sonicates under hypoxia. No alkylation was observed under aerobic conditions. Purified NADH:cytochrome b5 reductase catalyzed the reduction of mitomycin C with a Km of 23 microM at pH 6.6. At pH 7.6, the rate of enzymatic reduction of mitomycin C was 61% of that at pH 6.6. NADH:cytochrome b5 reductase catalyzed the activation of mitomycin C to alkylating metabolites under both hypoxic and aerobic conditions, with alkylation being 1.5 times greater in hypoxia. Dicumarol at 100 microM inhibited the NADH:cytochrome b5 reductase-catalyzed reduction of mitomycin C by 24% and by 57% at 300 microM. The degree of inhibition of the enzyme by dicumarol was the same at both pH 6.6 and 7.6. NADH:cytochrome b5 reductase exhibited a small but measurable NADH-oxidase activity, which was unaffected by 300 microM dicumarol. These findings demonstrate that (a) NADH:cytochrome b5 reductase can metabolically activate mitomycin C and (b) dicumarol is capable of inhibiting this enzymatic activity.

Aerobiosis↗
PubMed1996

The effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: a further report with 7 years of follow up.

PURPOSE: We determined the role, if any, of 1 and 5 instillations of intravesical mitomycin C in the treatment of newly diagnosed superficial bladder cancer. MATERIALS AND METHODS: A multicenter randomized clinical trial was done involving 502 patients with newly diagnosed superficial bladder cancer. After complete transurethral resection patients with newly diagnosed superficial bladder cancer. After complete resection patients were randomized into 1 of 3 treatment arms: no further treatment, 1 instillation of mitomycin C at resection and 1 instillation at resection and at 3-month intervals for 1 year (total 5 instillations). The dose of mitomycin C used was 40 mg./40 ml. water. End points were interval to first superficial recurrence, recurrence rate (defined as the number of positive cystoscopies per year) and progression-free interval rate (progression defined as the development of muscle invasive or metastatic disease, or death from bladder cancer). RESULTS: After median followup of 7 years 1 and 5 instillations of mitomycin C resulted in decreased recurrence rates and increased recurrence-free interval. The benefit of mitomycin C was observed in patients at low, medium and high risk for subsequent recurrence. There was suggestive but not conclusive evidence that 5 instillations of mitomycin C offered a slight advantage over 1 instillation. CONCLUSIONS: Our analysis confirms the positive benefit of mitomycin C to decrease the number of subsequent recurrences and increase the recurrence-free interval.

Administration, Intravesical↗
PubMed1997

The role of mitomycin treatment duration and previous intraocular surgery on the success of trabeculectomy surgery.

PURPOSE: This study was performed to determine the effect of duration of mitomycin exposure during trabeculectomy surgery on filtration success in eyes that had and had not been subjected to previous surgery. METHODS: On hundred six eyes of 92 patients were retrospectively reviewed. The effect of previous surgery and exposure duration of mitomycin 0.5 mg/ml on outcomes of trabeculectomy surgery were evaluated. RESULTS: The mean duration of mitomycin exposure was 0.7 +/- 0.02 min (mean +/- SEM) in the eyes that had not been subjected to previous surgery and 1.5 +/- 0.11 min in the eyes that had (p < 0.001). The mean follow-up times were 14 months in both groups. The mean decrease in intraocular pressure was 13.6 +/- 1.25 mm Hg in the group that had not been subjected to previous surgery and 13.9 +/- 1.45 mm Hg in the group that had been subjected to previous surgery. Analysis of variance techniques demonstrated no predictive value of demographics, history of previous surgery, or duration of mitomycin exposure with results of trabeculectomy surgery. Hypotony was the most frequent complication in both the no previous surgery and the previous surgery groups. The incidence of complications was numerically greater in the group that had not been subjected to previous surgery. CONCLUSIONS: The duration of mitomycin exposure and the history of previous surgery did not correlate with postoperative intraocular pressure, medications, or incidence of complications. The exposure duration response curve of mitomycin 0.5 mg/ml in these patients appears to be flat through the time evaluated. Lower concentrations of mitomycin and shorter exposure should be used to maintain efficacy with reduced risk of complications.

Adolescent↗
PubMed1985

Mitomycin-C plus metronidazole in advanced carcinoma of the breast.

Twenty-seven patients with metastatic adenocarcinoma of the breast refractory to other chemotherapy were treated with mitomycin-C plus metronidazole. The mitomycin-C dose was 15-20 mg/m2 I.V. repeated every 6-9 weeks. Metronidazole 1.5 g/m2 was given p.o. 12 hr and 1 hr before mitomycin-C and again 6 hr and 24 hr after mitomycin-C. Partial remissions were noted in 4 of 24 (17%) evaluable patients. Good performance status patients who were lightly pretreated, unresponsive to prior chemotherapy, and estrogen receptor negative were most likely to respond, and further studies are indicated in this subgroup of patients. Hematological toxicity was similar to that anticipated with mitomycin-C alone. Gastrointestinal toxicity was probably increased. Three probable and 2 possible cases of pulmonary toxicity were seen. It is unclear whether the incidence of mitomycin-C pulmonary toxicity was increased by the metronidazole.

Adenocarcinoma↗
PubMed1984

Sister chromatid exchanges after exposure to ultrasound and mitomycin C.

A pilot study was designed to determine whether a synergistic ability to produce sister chromatid exchanges exists between ultrasound and mitomycin C, an alkylating agent known to induce sister chromatid exchanges. Bromodeoxyuridine-containing cells from human lymphocyte cultures were randomized into one of four exposures: (1) unexposed controls, (2) 20 minutes of pulsed ultrasound (3.5 MHZ), (3) mitomycin C alone, or (4) mitomycin C and 20 minutes of pulsed ultrasound. The mean sister chromatid exchange frequencies were 6.7 control cells, 7.5 cells exposed only to ultrasound, 8.1 cells treated with both ultrasound and mitomycin C, and 10.4 cells treated with mitomycin C alone. Neither X2 tests for differences in the four distributions nor analysis of variance for interaction between ultrasound and mitomycin C was significant. Our results suggest that individuals receiving alkylating agents are not likely to be highly susceptible to any deleterious effects of ultrasound. However, these results remain tentative pending repetition of studies and development of more appropriate in vitro exposure systems.

Adult↗
PubMed1991

Spontaneous and mitomycin-C-induced micronuclei in human lymphocytes exposed to extremely low frequency pulsed magnetic fields.

The cytokinesis block micronucleus method, a very sensitive cytogenetic assay, was used to ascertain the possible genotoxic effects of extremely low frequency pulsed magnetic fields in phytohemagglutinin-stimulated human lymphocytes cultures from 16 healthy donors. Four conditions were studied: i) lymphocytes not exposed to the field (control cultures); ii) lymphocytes exposed to the field; iii) lymphocytes treated with mitomycin-C and not exposed to the field; iv) lymphocytes treated with mitomycin-C and exposed to the field. Mitomycin-C-treated cultures were used as control for the micronucleus method, because it is known that mitomycin-C is a potent genotoxic agent, capable of inducing micronuclei. The frequency of micronuclei in field-exposed cultures was similar to the spontaneous frequency observed in control unexposed-cultures. Moreover, the exposure to pulsed magnetic fields did not affect the frequency of micronuclei induced by mitomycin-C, suggesting that, in the experimental conditions used, this kind of field neither affected the integrity of chromosomes nor interfered with the genotoxic activity of mitomycin-C.

Alkylating Agents↗
PubMed1982

Metabolic activation of mitomycin C by liver microsomes and nuclei.

Bioreductive alkylating agents require reductive activation prior to exerting their cytotoxic actions. This property results in preferential toxicity to hypoxic cells. Previous data have demonstrated that mitomycin C is activated by hypoxic tumor cells and is selectively cytotoxic to these oxygen-deficient cells. The biotransformation of mitomycin C was studied in liver microsomes and nuclei and in a reconstituted, partially purified cytochrome P-450 drug-metabolizing system to provide information on these reductive processes. Both the metabolism of mitomycin C, measured by disappearance of the quinone portion of the substrate, and the formation of an alkylating metabolite(s), determined by employing 4-(p-nitrobenzyl)pyridine as a trapping agent, required anaerobic conditions and an NADPH-generating system, and were inhibited by O2 and CO in both microsomes and nuclei. A reconstituted enzyme system consisting of NADPH, NADPH-cytochrome P-450 reductase, phospholipid and cytochrome P-450 converted mitomycin C to a reactive metabolite(s) under hypoxic conditions. Omission of N2 or any component of the system decreased the metabolic activation of mitomycin C. These findings support the concept that the cytochrome P-450 system is capable of activating mitomycin C under hypoxic conditions to the alkylating metabolite(s) that is responsible for antineoplastic activity.

Alkylating Agents↗
PubMed1989

Intravesical mitomycin C instillation as a prophylactic treatment of superficial bladder tumor.

A study was performed to determine the prophylactic efficacy of intravesical mitomycin C instillation in 43 patients with recurrent (more than 3), multiple (more than 3) or large (more than 3 cm.) superficial bladder tumors (stage Ta or T1). Of the patients 21 were treated with 8 weekly intravesical instillations of 40 mg. mitomycin C after transurethral resection and 22 were followed conventionally. The recurrence rate was 42.9 per cent in the mitomycin C group and 40.9 per cent in the controls during the first 3 months, and it was 81.0 and 77.3 per cent, respectively during 24 months. Recurrences per 100 patient-months were 8.7 and 8.9, respectively. Two patients in the mitomycin C group and 4 controls had recurrent tumors with progression in stage. We conclude tentatively from these observations that intravesical mitomycin C instillation is not effective in the prophylaxis of tumor recurrence in patients at high risk. This finding is contrary to other reports indicating a marked decrease in recurrence with mitomycin C.

Administration, Intravesical↗
PubMedDate not supplied

Preparation of antigastric cancer monoclonal antibody MGb2-mitomycin C conjugate with improved antitumor activity.

In the present study, an antigastric cancer monoclonal antibody, MGb2, was chosen to prepare antibody-mitomycin C conjugate with dextran T-40 as intermediary. Up to 20 molecules of mitomycin C were specifically bound per molecule of antibody, without significantly impairing the antigen-binding capacity of the antibody and the pharmacological activity of mitomycin C. The conjugate showed selective cytotoxicity upon human gastric cancer cell line SGC-7901 in vitro. Radioimmunoimaging and biodistribution studies indicated that, after conjugation with mitomycin C via dextran T-40 as intermediary, the tumor localization capacity of the antibody was well-retained. When tested in nude mice inoculated with human gastric carcinoma GAII in bilateral subrenal capsules, intraperitoneal injection of the conjugate twice a week for 3 weeks at the dose of 1 mg/kg of drug gave a tumor inhibitory rate of 152.29%, the result being far better than that of free mitomycin C or an irrelevant conjugate. A similar result was found in another nude mouse model of human gastric carcinoma SGC-7901. Meanwhile, after conjugation with antibody, the toxicity of mitomycin C on tested animals was significantly reduced.

Animals↗