• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1845-1849
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• 2014

Background: There is no standard treatment for patients with colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability of raltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapy in mCRC patients. Materials and Methods: A total of 62 patients who had received raltitrexed combined with UFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6 $mg/m^2$ (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks (group A) or mitomycin C 6 $mg/m^2$ i.v. on day every 3 weeks (group B). Results: Forty-two patients (67.7%) were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resulting in dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival (PFS) was 3 months (95%CI 2.65-3.34) and median overall survival (OS) was 6 months (95%CI 2.09-9.90) in the whole group. Median PFS was 3 months (95%CI 2.60-3.39) in group A vs 3 months (95%CI 1.64-4.35) in group B (p=0.90). Median OS was 6 months (95%CI 2.47-9.53) in group A vs 12 months (95%CI 2.83-21.1) in group B (p=0.46). Conclusions: The combination of raltitrexed with UFT or mitomycin C seem to be a salvage therapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.525-533
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• 1997

Background : No ideal combination chemotherapy for lung cancer has been established even though lots of combination anticancer chemotherapies have been tried. For the combination of anticancer drugs, the interaction of anticancer drugs is very important but unpredictable factor. In this experiment, we designed and tested new experiment to measure the interaction of two anticancer drugs using MIT assay in an attempt to predict clinical response of the combination regimen. Methods : With human lung adenocarcinoma cell line (PC-14), the cytotoxic effect of cisplatin, adriamycin, mitomycin C and etoposide were measured by in vitro chemosensitivity test (MIT assay). The combined cytotoxic effects of combination of two drugs were also measured in every combination of the drug concentrations and analyzed the interaction by Anava analysis of two way factorial design. Results : Four individual drugs showed cytotoxic effects on PC-14 by dose dependent fashion. Comparison of two drug combinations revealed that mitomycin C + cisplatin and adriamycin + cisplatin combinations showed stronger synergistic cytotoxic effects. Conclusion : From this experiment, we suggest two combinations of mitomycin C + cisplatin and adriamycin + cisplatin as chemotherapeutic regimens for unresectable non-small cell lung cancer. Furthermore, this experimental design could be applied to other types of cancer requiring combination anticancer chemotherapy.

• Applied Microscopy
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• v.27 no.1
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• pp.13-30
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• 1997

The experiment was performed to study the morphological responses of the thymus of the mice, to antitumour agents (5-Fluorouracil or mitomycin C). Healthy adult mice weighing 25 gm each were divided into normal and experimental groups. 5-Fluorouracil (60 mg/kg) or Mitomycin-C $(400{\mu}g/kg)$ were injected subcutaneously to the animals every other day. Animals were sacrificed at 4 days and 7 days following the first injection. Pieces of the tissue taken from the thymus were prefixed with 2.5% paraformaldehyde-l.5% glutaraldehyde, followed by post-fixation with 1% osmium tetroxide. Ultrathin sections stained with uranyl acetate and lead citrate were observed with a JEM 100 CX-II electron microscope. The observed results were as follow: 1. Apoptoses of T-lymphocytes were observed more frequently in the thymus of the experimental groups than in those of a normal group. 2. In the experimental group, the plasma cells with distended cisternae of the granular endoplasmic reticulum and the eosinophile leukocytes were observed frequently. 3. In the experimental group, newly forming Hassall's corpurscles were observed frequently. 4. In the mitomycin-treated group, the epithelial reticular cells containing distended perinuclear cisternae, distended the granular endoplasmic reticula and pyknotic nuclei were observed in the cortico-medullary junctional area. 5. In the mitomycin-treated group, nuclear bodies with medium electron dense materials were often observed in the T lymphocyte. 6. In the 5-fluorouracil-treated groups, fused and dissolved tonofilament bundles and apoptotic bodies were observed in the some epithelial reticular cells in the medullary area. 7. In the 5-fluorouracil-treated groups, some elongated and bar-shaped lysosomes with electron lucent gap were often observed in the macrophages. 8. In the 5-fluorouracil-treated group, membrane complex of the smooth endoplasmic reticulum were ofen observed in the macrophage. From the above results, it was suggested that 5-fluorouracil or mitomycin could induce rapid involution of the thymus, and disturb maturation and differentiation of T lymphocytes, and, in turn, supress immunity.

• Applied Biological Chemistry
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• v.46 no.1
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• pp.32-38
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• 2003

Seventy percent ethanolic extracts from commercially available 13 legumes were made to investigated their antioxidative activities by determining the reducing power, inhibitory effect on lipid peroxidation, scavenging activity against both superoxide radical and hydroxyl radical, together with inhibitory activity toward mitomycin C-induced oxidative damage of DNA. High level of reducing powers were detected in Yepat, Sokpiri, Yuweol-bean and Jeokdu. Inhibitory effects on lipid peroxidation were found ubiquitously in all extracts examined when employing the linoleic acid autoxidation system, whereas, only 3 legumes, Yepat, Namul-bean and Jeenuni-bean, were revealed marked inhibition in rabbit erythrocyte-ghost membrane lipid peroxidation system. Yepat, Namul-bean, Jeokdu and Jeenuni-bean showed great scavenging activities on superoxide radical, on the other hand, high level of hydroxyl radical scavenging activities were demonstrated in Sokpiri, Chungtae, Yepat and Jebi-bean. Ubiquitous inhibitory effects on mitomycin C-induced oxidative damage on DNA were found in all extracts tested, Among them, however, Yepat, Jeenuni-bean, Namul-bean, Nokdu and Jeokdu showed the higher level of inhibition. Taken together, we could assign Yepat, Jeokdu, Jeenuni-bean and Sokpiri, for the legume species highly functional on overall antioxidative activity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4993-4998
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• 2012

Vanillic acid, a vegetable phenolic compound, is a strong antioxidant. The aim of the present study was to determine its effects on mitomycin C-induced DNA damage in human blood lymphocyte cultures in vitro, both alone and in combination with mitomycin C (MMC). The cytokinesis block micronucleus test and alkaline comet assay were used to determine genotoxic damage and anti-genotoxic effects of vanillic acid at the DNA and chromosome levels. MMC induced genotoxicity at a dose of $0.25{\mu}g/ml$. Vanillic acid ($1{\mu}g/ml$) significantly reduced both the rates of DNA damaged cells and the frequency of micronucleated cells. A high dose of vanillic acid ($2{\mu}g/ml$) itself had genotoxic effects on DNA. In addition, both test systems showed similar results when tested with the negative control, consisting of dimethyl sulfoxide (DMSO) in combination with vanillic acid ($1{\mu}g/ml$)+MMC. In conclusion, vanillic acid could prevent oxidative damage to DNA and chromosomes when used at an appropriately low dose.

• Korean Journal of Pharmacognosy
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• v.29 no.2
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• pp.93-103
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• 1998

In order to investigate the reducing effect of velvet antler water extract (VAWE) on the toxicity of anti-cancer drug, cis-platin (CDDP) and mitomycin C (MMC), we examined effects of co-administration with VAWE and anti-cancer drugs on their toxicities. We recognized that $LD_{50}$ of CDDP/MMC were increased by co-administration with VAWE and them in mice. It was found that co-administration of VAWE and MMC increased the survival rate in mice treated by lethal dose of MMC. Also, co-administration of VAWE and CDDP/MMC inhibited decrease of the body weight and organ weight in mice intoxificated by CDDP/MMC. The increase of serum blood urea and serum creatinine levels in rats intoxicated by CDDP were significantly inhibited by the co-administrationin with VAWE and CDDP. The decrease of RBC and WBC in rats intoxificated by MMC were significantly inhibited by the co-administration with VAWE and MMC. These results suggest that the combined usage of VAWE and CDDP/MMC drugs may be a new method for prevented or minimized the toxicity of them.

• Korean Journal of Food Science and Technology
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• v.34 no.6
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• pp.1115-1122
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• 2002

To evaluate the physiological properties of 22 varieties of legumes, antioxidative activity, antimutagenicity against Mitomycin C, genotoxicity, and mutagenicity were tested. Ethanolic extracts of legumes had significant antioxidative activities in the tests of electron-donating ability to DPPH radical, hydroxy radical-scavenging activity, and inhibitory effect on lipid auto-oxidation model system. Soy sprout bean (green), mung bean, and small black bean (green) had excitatory effects on the growth of E. coli PQ 37 cell. Black bean and green soy bean had inhibitory effects on the mutagenicities of the cells. Rice bean, pea, mung bean, and bonavista bean showed antimutagenic activities against chemical mutagen, Mitomycin C. Thus, rice bean and mung bean were found to be appropriate auxiliary ingredients of rice cake and rice processing food for the promotion of health and augmentation of rice and legume consumptions.

• Journal of Microbiology
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• v.44 no.5
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• pp.473-479
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• 2006

A well characterized naphthalene-degrading strain, Pseudomonas putida PpG7 was observed to utilize limonin, a highly-oxygenated triterpenoid compound as a sole source of carbon and energy. Limonin concentrations evidenced a 64% reduction over 48 h of growth in batch cultures. Attempts were made to acquire a plasmid-less derivative via various methods (viz. Ethidium Bromide, SDS, elevated temperature & mitomycin C), among which the method involving mitomycin C ($20{\mu}g/ml$) proved successful. Concomitant with the loss of plasmid in P. putida PpG7 strain, the cured derivative was identified as a $lim^-$ phenotype. The $lim^+$ phenotype could be conjugally transferred to the cured derivative. Based on the results of curing with mitomycin C, conjugation studies and presence of ndo gene encoding naphthalene 1,2 dioxygenase, it was demonstrated that genes for the limonin utilization were encoded on an 83 kb indigenous transmissible Inc. P9 NAH plasmid in Pseudomonas putida PpG7 strain.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.92-100
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• 2004

Effect of the depletion or oxidation of GSH on mitomycin c (MMC)-induced mitochondrial damage and cell death was assessed in small cell lung cancer (SCLC) cells. MMC induced cell death and the decrease in the GSH contents in SCLC cells, which were inhibited by z-LEHD.fmk (a cell permeable inhibitor of caspase-9), z-DQMD.fmk (a cell permeable inhibitor of caspase-3) and thiol compound, N-acetylcysteine. MMC caused nuclear damage, release of cytochrome c and activation of caspase-3, which were reduced by N-acetylcysteine. The depletion of GSH due to L-butionine-sulfoximine enhanced the MMC-induced cell death and formation of reactive oxygen species in SCLC cells, whereas the oxidation of GSH due to diamide or $NH_2Cl$ did not affect cytotoxicity of MMC. The results show that MMC may cause cell death in SCLC cells by inducing mitochondrial dysfunction, leading to activation of caspase-9 and -3. The MMC-induced change in the mitochondrial membrane permeability, followed by cell death, in SCLC cells may be significantly enhanced by the depletion of GSH. In contrast, the oxidation of GSH may not affect cytotoxicity of MMC.

• Applied Microscopy
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• v.44 no.3
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• pp.88-95
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• 2014

This study examined the effects of quercetin on corneal opacity caused by corneal edema by suppressing the damage on corneal endothelial cell, which was induced by mitomycin-C (MMC). In the MMC-treated group, the number of keratocytes was noticeably fewer compared to that of other groups. Although this group showed normal amount of fiber in the corneal stroma, the thickness was shown to be very thick and the alignment of the corneal endothelial cells that worked as the barrier against aqueous humor was irregular. According to such results, it was known that corneal opacity induced by MMC is not caused by proliferation of keratocytes, but by corneal edema triggered by the infiltration of aqueous humor. In the MMC+quercetin and quercetin+MMC-treated groups, the number of keratocytes was higher and polymorphonuclear leukocytes infilteration was lower significantly compared to that of the MMC-treated group. Although the amounts of fiber and endothelioid cell arrangement were normal, there was more space observed in the corneal stroma. Nonetheless, these groups showed significantly lower stromal thickness compared to that of the MMC group. In conclusion, quercetin has the effect on the reduction of corneal opacity caused by corneal edema that work MMC-induced damage to the corneal endothelial cells.