• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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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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• 제44권3호
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• pp.525-533
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• 1997

연구배경 : 수술적 절제가 불가능한 폐암환자에서 복합화학요법의 역할이 최근 증대되고 있으나 아직 가장 이상적인 복합화학요법은 확립되지 않고 있다. 두 종류 이상의 항암제를 복합투여시 약제간의 상호작용에 의해 항암효과의 상승 혹은 억제를 보일 수 있으나 이를 예측하기가 어려웠다. 본 연구에서는 MTT 검사를 이용하여 두 약제를 여러 농도에서 복합투여후 살해능의 변화를 관찰하였다. 방 법 : 사람의 폐선암세포인 PC-14를 이용하여 cisplatin, mitomycin C, adriamycin 및 etoposide를 여러 농도에서 단독 또는 두 약제를 복합투여하여 항암효과의 변화를 MTT 검사로 측정하고 두 약제 복합투여시의 상호 작용의 결과를 이원배치법을 이용한 Anova분석을 이용하여 측정하였다. 결 과 : 위의 네종류의 약제는 단독투여시 농도에 비례하는 암세포살해능을 보였고 두 약제를 복합투여시 모든 조합에서 암세포살해능의 상승효과를 보였으며 특히 mitomycin C 와 cisplatin 및 adriamycin과 cisplatin을 복합투여시 상승효과가 강하게 나타났다. 결 론 : 위의 결과로 비소세포폐암의 복합화학요법시 mitomycin C와 cisplatin 혹은 adriamycin과 cisplatin을 같이 사용할 경우 항암효과의 극대화를 얻을 수 있으리라 기대된다. 나아가 이번 연구의 디자인은 복합항암화학요법을 필요로 하는 모든 종류의 암에 적용되어 최대항암효과를 얻을 수 있는 약제선정에 도움의 될 수 있으리라 생각된다.

• Applied Microscopy
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• 제27권1호
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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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• 제46권1호
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• pp.32-38
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• 2003

시판되고 있는 두류 13종류의 70% 에탄을 추출물을 제조하여, 이들의 항산화 활성을 환원력, 지질과산화 억제 활성, superoxide radical 소저활성, hydroxyl radical 소거활성, mitomycin C로 유도된 DNA의 산화적 손상에 대한 억제활성을 지표로 조사하였다. 환원력은 예팥, 속피리, 유월콩 및 적두가 높았다. 지질과산화 억제능을 조사한 결과, linoleic acid 자동산화계를 이용한 실험계에서 모든 시료가 억제활성을 보인 반면, 토끼 적혈구막 지질과 산화에 대한 억제활성은 쥐눈이콩과 적두, 속피리에서만 관찰되었다. Superoxide radical 소거활성은 예팥, 나물콩, 적두, 쥐눈이콩에서 높게 나타났으며, hydroxyl radical 소거활성은 속피리, 청태, 예팥과 제비콩에서 높았다. Mitomycin C로 유도된 DNA의 산화적 손상에 대한 억제활성을 조사한 결과, 모든 품종들이 DNA의 산화적 손상을 억제할 수 있었으나, 특히 예팥, 쥐눈이콩, 나물콩, 녹두, 적두의 억제활성이 우수하였다. 이상의 실험결과에서 예팥, 적두, 쥐눈이콩, 속피리가 환원력, 지질과산화 억제, superoxide radical 및 hydroxyl radical 소거활성, DNA의 산화적 손상에 대한 억제활성 둥 항산화활성이 우수한 품종임을 알 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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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.

• 생약학회지
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• 제29권2호
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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.

• 한국식품과학회지
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• 제34권6호
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• pp.1115-1122
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• 2002

시판되고 있는 두류 22 종류의 70% 에탄올 추출물을 제조하여, 이들의 항산화 활성, 화학적 변이원 mitomycin C에 대한 항변이원성, 세포독성, 변이원성 등을 포함하는 생리활성 효과를 비교 검정하였다. DPPH radical에 대한 전자공여능, hydroxy radical 소거능 및 지질 자동산화 억제효과 등은 모든 두류 품종이 거의 유사한 효과를 나타내었다. 예팔, 완두, 녹두, 백편두 등은 변이원 mitomycin C에 대해 유의할만한 수준의 항변이원성을 보였으며, 녹색나물콩, 녹두, 속피리 등은 지시 세포의 성장을 촉진하는 효과가 있었고, 속청과 청태는 변이원성을 억제하는 특성이 있었다. 백편두는 세포 성장과 돌연변이 유발 모두를 억제하는 것으로 나타나 추출물 자체가 독성을 가질 수도 있을 것으로 생각되었다. 결과적으로 본 연구의 목적이었던 기능성 밥 및 떡 제조를 위한 부재료로서의 두류 이용을 위해서는 예팥, 녹두 등을 이용하는 것이 바람직하리라고 생각된다.

• Journal of Microbiology
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• 제44권5호
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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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• 제12권2호
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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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• 제44권3호
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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.