Posterior scleral application of a mitomycin C-soaked sponge during trabeculectomy

AIM:To evaluate the safety and efficacy of posterior scleral application(a modified technique)of an antimetabolite mitomycin C-soaked sponge in trabeculectomy for patients with glaucoma.METHODS:This retrospective study included 101 patients(115 eyes)with glaucoma(aged 12–83y)who underwent trabeculectomy using a modified mitomycin C-soaked sponge placement method.A piece of 3.5×10 mm2 sponge was placed vertically and posteriorly with the long side perpendicular to the limbus.The mitomycin C concentration and exposure time were 0.2–0.5 mg/m L and 1–5min,respectively.Intraocular pressure,bestcorrected visual acuity,and hypotensive medications were recorded at baseline and at the final visit.Complications,interventions required,and bleb morphology were recorded postoperatively.The primary outcome was trabeculectomy safety,including complications and bleb morphology;the secondary outcome was the trabeculectomy success rate.RESULTS:At the final follow-up[median 28mo,range 7–67mo and interquartile range(IQR)13mo],the qualified(cumulative)success rate was 93.0%and the complete success rate was 60.0%.No bleb-related complications were observed.The mean height,extent,and vascularity grades were 0.6±0.9,1.1±0.4,and 2.4±0.9,respectively.All Seidel tests were negative.The mean posteriority grade was 0.8±0.4.CONCLUSION:Trabeculectomy with the long side of a mitomycin C-soaked sponge placed perpendicular to the corneal limbus is safe and effective.

Mitomycin C and capecitabine: An additional option as an advanced line therapy in patients with metastatic colorectal cancer

BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.

Studies on Mitomycin C Dextran-microspheres

In this paper,the preparation and properties of mitomycin C dextran-microspheres(MMC-DMS)were reported.The characteristics of pharmacokinetics and embolization effects of MMC-DMS in vivo were studied in dogs.The average diameter of the microspheres was 75±19μm and the content was 5% of MMC.In in vitro experiment, the release rate of drug demonstrated that the microspheres had sustained-release properties. The microspheres and conventional MMC were infused into the hepatic artery of dogs through a catheter for embolization,respectively.The plasma concentration of MMC was de- termined by HPLC.Results showed that the peak concentration of conventional MMC was 2.6 times as much as MMC-DMS.Angiograms revealed that peripheral blood vessels de- creased obviously in liver.The histopathologic examination showed that the microspheres lodged in the hepatic artery and displayed nodular necrosis in the embolized segment.The MMC-DMS were used in clinical trial in 100 patients with hepatic cancer.The tumor reduc- tion and improvement of symptoms in patients were observed after hepatic arterial embolization.The survival duration was prolonged.Results showed that the MMC-DMS is a promising embolic agent for treatment of hepatic cancer.It could aid in the use of intensive chemotherapy with minimum systemic side effect.

Interaction between Mitomycin C and DNA at Paraffined Graphite Electrode

Aim To investigate the electrochemical behaviors of Mitomycin C （MC） and its interaction with calf thymus DNA （ctDNA）. Methods The cyclic vohammetry （CV） was carried out at a paraffined graphite electrode. Results MC showed a well-defined oxidation-reduction peak. As a result of reaction with ctDNA, the peak current of MC decreased apparently. According to corresponding electrochemical equations, the diffusion coefficient of both free and MC-DNA complex have been determined, and the heterogeneous rate constants were also obtained simultaneously. Conclusion The solid paraffined graphite electrode could be used to estimate parameters of the interaction between DNA and MC, and provide the convenient and sensitive analysis.

Mitomycin C induces apoptosis in human epidural scar fibroblasts after surgical decompression for spinal cord injury

Numerous studies have shown that topical application of mitomycin C after surgical decompression effectively reduces scar adhesion. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of mitomycin C on the proliferation and apoptosis of human epidural scar fibroblasts. Human epidural scar fibroblasts were treated with various concentrations of mitomycin C （1, 5, 10, 20, 40 μg/mL） for 12, 24 and 48 hours. Mitomycin C suppressed the growth of these cells in a dose- and time-dependent manner. Mitomycin C upregulated the expression levels of Fas, DR4, DR5, cleaved caspase-8/9, Bax, Bim and cleaved caspase-3 proteins, and it downregulated Bcl-2 and Bcl-xL expression. In addition, inhibitors of caspase-8 and caspase-9 （Z-IETD-FMK and Z-LEHD-FMK, respectively） did not fully inhibit mitomycin C-induced apoptosis. Furthermore, mitomycin C induced endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78, CAAT/enhancer-binding protein homologous protein （CHOP） and caspase 4 in a dose-dependent manner. Salubrinal significantly inhibited the mitomycin C-induced cell viability loss and apoptosis, and these effects were accompanied by a reduction in CHOP expression. Our results support the hypothesis that mitomycin C induces human epidural scar fibroblast apoptosis, at least in part, via the endoplasmic reticulum stress pathway.

Study of Low-intensity 2450-MHz Microwave Exposure Enhancing the Genotoxic Effects of Mitomycin C Using Micronucleus Test and Comet Assay in vitro

Objective To determine the interaction between 2450-MHz microwaves (MW) radiation and mitomycin C (MMC). Methods The synergistic genotoxic effects of low-intensity 2450-MHz microwave and MMC on human lymphocytes were studied using single cell gel electrophoresis (SCGE) assay (comet assay) and cytokinesis-blocked micronucleus (CBMN) test in vitro. The whole blood cells from a male donor and a female donor were either only exposed to 2450-MHz microwaves (5.0 mW/cm2) for 2 h or only exposed to MMC (0.0125 μ/mL, 0.025 μg/mL, 0.05μg/mL and 0.1 μg/mL) for 24 h; and the samples were exposed to MMC for 24 h after exposure to MW for 2 h. Results In the comet assay, the comet lengths ( 29.1 μm and 25.9 μm) of MW were not significantly longer than those (26.3 μrn and 24.1 μm) of controls (P>0.05). The comet lengths (57.4 μm, 68.9 μm, 91.4 μm, 150.6μm and 50.6 μm, 71.7μm, 100.1 μm, 145.1 μm) of 4 MMC groups were significantly longer than those of controls (P<0.01). The comet lengths (59.1 μm, 92.3 μm, 124.5 μm, 182.7 μm and 57.4 μm, 85.5 μm, 137.5 μm, 178.3 μm) of 4 MW plus MMC groups were significantly longer than those of controls too (P<0.01). The comet lengths of MW plus MMC groups were significantly longer than those of the corresponding MMC doses (P<0.05 or P<0.01) when the doses of MMC were ≥50.025 μg/mL. In the CBMN, the micronucleated cell (MNC) rates of MW were 5% and 6%, which showed no difference compared with those (4‰ and 4‰) of controls (P>0.05). The MNC rates of 4 MMC groups were 8‰, 9‰, 14‰, 23‰ and 8‰, 8‰, 16‰, 30‰ respectively. When the doses of MMC were 3≥0.05 μg/mL, MNC rates of MMC were higher than those of controls (P<0.05). MNC rates of 4 MW plus MMC groups were 12‰, 13‰, 20‰, 32‰ and 8‰, 9‰, 23‰, 40‰. When the doses of MMC were 5≥0.05 μg/mL, MNC rates of MW plus MMC groups were much higher than those of controls (P<0.01). MNC rates of 4 MW plus MMC groups were not significantly higher than those of the corresponding MMC doses. Conclusion The low-intensity 2450-MHz microwave radiation can not induce DNA and chromosome damage, but can increase DNA damage effect induced by MMC in comet assay.

Bare sclera resection followed by mitomycin C and/or autograft limbus conjunctiva in the surgery for pterygium:a Meta-analysis

AIM: To evaluate the recurrence and complications after bare sclera resection (BSR) combined with mitomycin C (MMC) treatment and/or autograft limbus conjunctiva (ALC) in the surgery for pterygium. METHODS: Meta -analysis was used to evaluate the differences in patient outcomes between BSR of pterygium with or without MMC and/or ALC. All included studies were randomized trials of patients with pterygium who received BSR followed by MMC and/or ALC in the surgery. The recurrence of pterygium and other complications resulting from different treatments were extracted for analysis. RESULTS: Thirteen studies met the inclusion criteria. The recurrence of pterygium with intraoperative (10) MMC was higher than that with ALC (OR=2.38,95% confidence interval 1.45-3.91, I-2=29%). Postoperative MMC resulted in an incidence of recurrence similar to that of ALC (OR= 0.66, 95% confidence interval 0.30-1.42, I-2=0%), and 10 MMC treatment in combination with ALC produced similar patient outcomes to ALC alone (OR =0.41, 95% confidence interval 0.16-1.01, I-2=16%). Other complications such as punctate epitheliopathy, scleral thinning and ischemia, irritation and persistent epithelium defect, were more common in patients in the MMC group as compared to those treated with ALC. CONCLUSION: The recurrence of pterygium with BSR followed by ALC is lower than that of BSR followed by MMC, and the incidence of other complications is lower. While ALC is a more effective strategy for treating pterygium, the quality of the ALC transplant should be considered when the patient has a history of glaucoma.

Mitomycin C in pterygium treatment

Pterygium is a benign lesion usually growing from the nasal side of the conjunctiva onto the cornea.Most cases of pterygium does not cause problem or requires specific treatment.The exact cause of pterygium is not clear yet,but some factors are pointed as causes,being the most important the long-term ultraviolet ray exposure.Pterygium surgery is usually considered when there are symptoms that do not respond to conservative treatment.Recurrence is the main complication of the surgery,and much has been done to avoid it.Mitomycin C（MMC） has been used as a fibroblast proliferation inhibitor during the surgery to reduce the chance of recurrence of the pterygium.This review describes the use of MMC as an adjunctive,the optimal dosage,the duration of administration of MMC and possible complications,when used during,after and before the surgery.Most studies suggest that increased exposure（dose or duration） of MMC is associated with a lower recurrence,but with higher risks of complications.

Safety and efficacy of photodynamic therapy using BCECF-AM compared to mitomycin C in controlling post-operative fibrosis in a rabbit model of subscleral trabeculectomy

AIM： To evaluate the safety and efficacy of cellular photoablation using BCECF-AM [2, T-bis-（2-carboxyethyl） -5-（and-6）-carboxyfluorescein, acetoxymethyl ester mixed isomersl as a method to control postoperative fibrosis in subscleral trabeculectomy （SST） compared to mitomycin C （MMC） in a rabbit model. METHODS： A comparative prospective case-control animal study was conducted. Fourteen rabbits were subjected to SST with intraoperaUve use of wound modulating agents （MMC or BCECF-AM） of the right eye （study groups I and II respectively） and SST without use of intraoperative wound modulating agents for the left eye （control group II）. Two rabbits 4 eyes were considered as control group I with no surgical intervention. BCECF-AM was injected subconjunctivally 30min before surgery followed by intraoperative illumination with diffuse blue light for 10min. Antifibrotic efficacy was established by clinical response and histological examination. Clinical response was assessed by measuring intraocular pressure （lOP） at day 1, 3, 5, 7, 14, 21 postoperatively, Success was defined by 〉20.0% reduction in lOP from the preoperative values without anti-glaucoma medications. RESULTS： The mean percentage of reduction was 35.0% in the study group I with only one eye （14.3%） had 12.5% reduction. The mean percentage of reduction was 28.0% in the study group U with two eyes （28.6%） in study group II had 14.2% reduction each. Regarding the control group II, the mean percentage of reduction was 14.3% with 64.3% eyes had 〈20.0% reduction. There was a highly statistically significant difference between each of the study groups （right eyes） and the corresponding control group II （left eyes） as regards the mean postoperative lOP values started from day 5 in both study groups and this highly significant difference remained so till the end of the follow up period. Histologically, MMC treated blebs showed thinning of conjunctival epithelium with marked reduction of the goblet cells relative to control. Marked sub-epithelial edema was seen along with variable collagen dispersion. Mild cellularity was noted in sub-epithelial tissue. BCECF-AM treated blebs showed normal conjunctival epithelial thickness with abundant goblet cells. Mild sub- epithelial edema was noted along with moderate collagen dispersion. No histological abnormality was noted in the ciliary body or the cornea in any of the studied groups. CONCLUSION： Cellular photoablation using BCECF-AM is a safe and effective wound modulating agent to control postoperative fibrosis in trabeculectomy. However MMC considered as a more potent adjuvant to trabeculectomy than BCECF-AM in promoting IOP reduction.

Smac/DIABLO Promotes Mitomycin C-induced Apoptosis of Bladder Cancer T24 Cells

The enhancing effects of Smac gene on the mitomycin C-induced apoptosis of the bladder cancer cell line T24 were investigated. The Smac gene was transfected into bladder cancer cell line T24 under the induction of liposome. The intrinsic Smac level was detected by using immunohistochemistry and RT-PCR. The in vitro cellular growth activities were assayed by MTT colorimetry. Apoptosis was assayed by the flow cytometry. The results showed that as compared with the control cells, the apoptosis rate of T24 cells induced by mitomycin C was enhanced by transfected Smac gene. Flow cytometry revealed that, the apoptosis rate was 18.84 % and 33.52 %, and 10.72 % and 26.24 % respectively in blank and transfected cells treated with 0.05 or 0. 005 mg/mL mitomycin C （P〈0.05）. It was concluded that Smac could enhance the apoptosis of T24 by mitomycin C, which could provide a useful experimental evidence for bladder cancer therapy.

A Study in vitro on the Synergetic Cytocidal Effect ofAscorbic Acid and Mitomycin C against the Ehrlich As-cites Tumor Cells in Culture

The synergetic cytocidal effect of ascorbic acid and mitomycin C on Ehrlich as-cites tumor cells in culture was studied. The chain scission of DNA by Cu(Ⅱ)mitomycin C/ascorbic acid system,and the chemical kinetics of the Cu(Ⅱ) catalyzed aerobic oxidation of ascorbic acid in the presence of mitomycin C were also discussed. Experimental results showed that ascorbic acid and mitomycin C were synergetic in destroying Ehrlich ascites tumor cells.The effect is related to the breaking action of the Cu(Ⅱ)mitomycin C/ascorbic acid system on the DNA chain, and to the quantity of the system produced ·OH, and the speed of production which are both directly proportional to the concentration of ascorbic aci.These results imply that the ·OH produced in the aerobic oxidation of ascorbic acid,and·OH induced scission of DNA chain, are important factors to he synergetic cytocidal effect of ascorbic acid and mitomycin C on Ehrlich ascites tumor cells.

Potential risk of mitomycin C at high concentrations on peripheral nerve structure

Although the local application of mitomycin C may prevent epidural adhesion after laminectomy, mitomycin C can induce neurotoxicity in optic and acoustic nerves at high concentrations. To determine the safe concentration range for mitomycin C, cotton pads soaked with mitomycin C at different concentrations （0.1, 0.3, 0.5, and 0.7 mg/mL） were immediately applied for 5 minutes to the operation area of rats that had undergone laminectomy at L1. Rat sciatic nerves, instead of dorsal nerves, were used in this study. The results showed that mitomycin C at 0.1-0.5 mg/mL did not damage the structure and function of the sciatic nerve, while at 0.7 mg/mL, mitomycin C signiifcantly reduced the thickness of the sciatic nerve myelin sheath compared with lower concen-trations, though no functional change was found. These experimental ifndings indicate that the local application of mitomycin C at low concentrations is safe to prevent scar adhesion following laminectomy, but that mitomycin C at high concentrations （＆gt;0.7 mg/mL） has potential safety risks to peripheral nerve structures.

Study on the Interaction of Mitomycin C with ct-DNA by Pd-Porphin Room Temperature Phosphorescence Probe

Anticancer drug Mitomycin C (MMC) quenches remarkably phosphorescence and reduces lifetime of phosphorescence probe, Pd-meso-tetrakis-(4-trimethylaminophenyl)porphin (Pd-TAPP), in the presence of calf thymus DNA. These results may be attributed to the site competition of MMC with the probe and electron transfer between MMC and probe. MMC also increases polarization degree of the probe by covalent drug-DNA or DNA-drug-DNA crosslinking.

Deep sclerectomy-trabeculectomy with mitomycin C in treating glaucoma:postoperative long-term results

AIM:To determine the long-term postoperative outcomes of deep sclerectomy-trabeculectomy(DST)with mitomycin C(MMC)in the treatment of glaucoma.METHODS:Patients who underwent DST with MMC between 2010 and 2017 were included in this retrospective observational study.Complete success was defined as postoperative intraocular pressure(IOP)≤21 mm Hg or 30%reduction of IOP from baseline without any topical IOP-lowering agent,and qualified success defined as IOP≤21 mm Hg or 30%reduction of IOP from baseline with/without single topical agent.We evaluated the surgical success rates and complication rates of this procedure,as well as described the IOP profiles,best corrected visual acuity(BCVA)profiles and mean deviations(MD)of Humphrey visual field(HVF)24-2 performance at each follow-up time point.Mixed linear regression models were constructed to determine estimated predictive values of demographic data,use of topical IOPlowering agents,baseline and postoperative IOP and optical profiles(e.g.,BCVA and MD).RESULTS:Totally 98 eyes(mean postoperative followup 67.5mo)showed mean IOP reduction at every followup interval.Both median BCVA and MD of visual fields were maintained throughout the follow-up intervals when comparing to baseline.The number of IOP-lowering medications decreased from 2.8±0.8 to 0.3±0.7(P=0.068).Totally 84(85.7%)eyes achieved complete success at final follow-up.Transient hyphaema and transient choroidal effusion developed in 15 eyes(15.3%)and 11 eyes(11.2%)respectively.Other complications included shallow anterior chamber in 5 eyes(5.1%),bleb leak in 4 eyes(4.1%),bleb revision in 7 eyes(7.1%),bleb needling in 9 eyes(9.2%)and repeat trabeculectomy in 1 eye(1.0%).There was no endophthalmitis,blebitis or macular oedema.There was no significant correlation between postoperative IOP control and postoperative BCVA.CONCLUSION:DST with MMC demonstrates effective and sustained long-term outcomes in the treatment of glaucoma with no major complication.

Trabeculectomy with Ologen implant versus mitomycin C in congenital glaucoma secondary to Sturge Weber Syndrome

AIM： To compare the efficacy and safety of collagen matrix implant [Ologen（OLO） implant] versus mitomycin C（MMC） with subscleral trabeculectomy（SST） for the surgical treatment of congenital glaucoma（CG） in SturgeWeber Syndrome（SWS）.METHODS： A prospective comparative randomized study of 20 eyes of 16 patients with CG associated with SWS was divided into two groups. The first group（MMC Group） included 10 eyes that were subjected to SST with MMC. The second group（OLO Group） included 10 eyes that were subjected to trabeculectomy with a collagen matrix implant（OLO implant）. Postoperative evaluation included intraocular pressure（IOP） level, bleb evaluation, complications, and the need for further medication or surgical intervention. RESULTS： The mean preoperative IOP was 29±3.16 mm Hg in MMC and 29.8±3.08 mm Hg in OLO eyes. Mean 12-month percentage reduction in IOP was significant in both groups（57.9% and 56.3%）. At the end of the 12 postoperative follow-up month, in the MMC Group, 80% of eyes achieved the complete success, 20% of eyes had qualified success with no failed surgery in comparison to OLO Group which 70% of eyes achieved the complete success, 20% of eyes had qualified success with 10% failed surgery. In terms of complications, the MMC Group had a higher rate of complications than the OLO Group in the form of thin polycystic bleb in 6 eyes（60%）, blebitis in only one eye（10%） treated with topical antibiotics, shallow anterior chamber in two eyes（20%）.CONCLUSION： This study proves that the use of a collagen matrix implant yields equally effective results as MMC when combined with trabeculectomy for the treatment of CG in SWS. Furthermore, OLO implantation is safe and has low incidences of complications.

Evidence of increased chromosomal instability in infertile males after exposure to mitomycin C and caffeine

Aim： To evaluate the genetic instability of 11 fertile and 25 infertile men. Methods： The methodology of sister chromatid exchanges （SCEs） was applied to cultures of peripheral blood lymphocytes, and the levels of SCEss were analyzed as a quantitative index of genotoxicity, along with the values of the mitotic index （MI） and the proliferation rate index （PRI） as qualitative indices of cytotoxicity and cytostaticity, respectively. The genotoxic and antineoplastic agent, mitomycin C （MMC）, and caffeine （CAF） - both well-known inhibitors of DNA repair mechanism - were used in an attempt to induce chromosomal instability in infertile men, so as to more easily detect the probable underlying damage on DNA. Results： Our experiments illustrated that infertile men, compared with fertile ones, demonstrated a statistically significant DNA instability in peripheral blood lymphocytes after being exposed simultaneously to MMC and CAF. Conclusion： The current study showed vividly that there was genetic instability in infertile men which probably contributes to the development of an impaired reproductive capacity. （Asian JAndro12006 Mar; 8： 199-204）

Short-term outcomes of mitomycin C-augmented excisional bleb revision with capsulectomy for failed Ahmed glaucoma valve

AIM: To report short-term outcomes of mitomycin C-augmented excisional bleb revision with capsulectomy(ERC) after Ahmed glaucoma valve(AGV) failure.METHODS: Patients who underwent ERC procedures between January 2017 and December 2019 with a minimum follow-up of 6mo were evaluated retrospectively for indications of AGV and AGV implantation to ERC interval.The number of anti-glaucoma medications(AGMs),intraocular pressure(IOP) and best corrected visual acuity(BCVA) were recorded at baseline, 1, 7, 30, 90, and 180d.Intra-and postoperative complications were also recorded.Positive outcome was defined as IOP≤21 mm Hg with or without AGMs.RESULTS: Fourteen eyes [14 patients, median age 69.5y, interquartile range(IQR) 61.3-80] were included.Pseudoexfoliative glaucoma(n=5, 36%) was the most common form of glaucoma. The median AGV implantation to ERC interval was 8.8mo(IQR 3.91-43.67). At 6mo, the median number of AGMs decreased from 3.0(IQR 3.0-4.0)to 2.0(IQR 1.5-3), the median IOP decreased from 26 mm Hg(IQR 22-29) to 16.5 mm Hg(IQR 13.75-20) and there was no significant change in BCVA. The success rate at 6mo was 92.9%. The Kaplan-Meier cumulative probability of survival was 93%, 79%, 64%, and 64% at 1wk, and 1,3, and 6mo, respectively. No intraoperative complications were identified. Postoperative complications were identified in 5 eyes(36%), which were resolved spontaneously during the first week following ERC.CONCLUSION: ERC has a high success rate for shortterm management of AGV failure. A longer follow-up study is required to determine long-term cumulative failure rates.

PRE-EXPOSURE OF MICE TO LOW DOSE OR LOW DOSE RATE IONIZING RADIATION REDUCES CHROMOSOME ABERRATIONS INDUCED BY SUBSEQUENT EXPOSURE TO HIGH DOSE OF RADIATION OR MITOMYCIN C

The phenomenon of cytogenetic adaptive and cross-adaptive response induced by low dose irradiation and chemical mutagen in mice is described. We found, firstly, that adaptation can be induced by acute low dose Xirradiation (0-100 mGy). Secondly, a cross-adaptation can occur between X-irradiation and mitomycin C (MMC). And finally, mice pre-exposed to chronic low dose rate￣(60)Co-Gamma irradiation (0-226.0 mGy/day) are less susceptible to chromosome aberration induced by subsequent acute higher Xirradiation. Therefore, our data suggest that radioadaptive response depends on dose, dose rate and time interval. Possible mechanisms are also discussed.

Phase Ⅱ study of mitomycin C and cisplatin in heavily pretreated advanced breast cancer

Objective： The mitomycin C and cisplatin combination was investigated in patients with advanced breast cancer who had been exposed to anthracyclines, vinorelbine and taxanes. Methods： Three-weekly regimen consisted of mitomycin, 6 mg/m^2 administered intravenously on day 1, and cisplatin, 25 mg/m^2 intravenously on day 1-3. Results： Thirty-eight patients aged 25-75 years （median, 46 years） were treated with an overall response rate of 31.6%. The median time to progression （TTP） was 4.0 months. Median TTP for 12 patients with a complete or partial response was 9.0 months, while stable disease and progression of disease 4.0 months, P=0.002. Grade 3/4 side effects of neutropenia, thrombocytopenia and nausea/vomiting were documented in 4 （10.5%）, 4 （10.5%） and 3 （7.9%） patients, respectively. The median overall survival was 13＊ months. Conclusion： Mitomydn C/cisplatin doublet showed antitumor activity for anthracydine-, vinorelbine- and taxane-resistant breast cancer comparable to other regimens. This well-tolerated regimen provides an affordable option for patients in China.

Chronic model of tympanic perforation in rats with mitomycin C and dexamethasone

A rat model of chronic tympanic membrane perforation was developed to be used in the search of new materials for the sealing of these perforations. A longitudinal study was carried out in rats subjected to incisional myr-ingotomy followed by the application of mitomycin C alone or with dexamethasone. Rats were checked at days 3, 7,1 0,1 4 and weekly thereafter until perforation closure, for up to 6 months. The addition of dexamethasone is a key component in order to obtain a chronic opening. Myringotomies treated w ith saline had a mean healing time of 8.5 days. At 8 weeks, between 62.5% and 77.7% of tympanic membranes treated w ith mitomycin C and dexamethasone remained perforated and at 6 months this number fell to 21.4%. This technique is able to maintain most tympanic membrane perforations patent for at least 8 weeks. This rat model is adequate for its use in preclinical or translational research.