BACKGROUND: Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. METHODS: A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. RESULTS: Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. CONCLUSION: Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene. Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.
Humans ; Lung Neoplasms ; Genes, p53 ; Antimetabolites

PURPOSE: In order to analyze the clinical efficacy of amniotic membrane transplantation, this study reviewed the literature on the treatments of pterygium with antimetabolites, radiation and conjunctival autograft. In addition, the outcome of simple excision with preserved human amniotic membrane transplantation in the treatment of a primary and recurrent pterygium were assessed. METHODS: A total of 28 eyes with pterygium (primary 11 eyes, recurrent 17 eyes) were treated with a simple excision and a preserved human amniotic membrane transplantation. A recurrence was defined as a regrowth of fibrovascular tissue invading the cornea. RESULTS: During a mean follow-up of 86 days, 2 (7%) recurrences were observed. One out of 11 eyes had a recurrence of the primary pterygium (9%), 1 out of 17 eyes had a recurrence of the recurrent pterygium (6%). No side effects or complications were observed. CONCLUSIONS: The simple excision of pterygium with amniotic membrane transplantation had a low recurrence rate and no side effects. The amniotic membrane transplantation is an effective method for treating pterygium.
Amnion* ; Antimetabolites ; Autografts ; Cornea ; Follow-Up Studies ; Humans ; Pterygium* ; Recurrence

Inspite of technical advances, the need for pharmacologic treatment of proliferative vitreoretinopathy was increased. In order to evaluate the antiproliferative effect of various antimetabolites to the rabbit retinal pigment epithelial cell, we treated cultured rabbit retinal pigment epithelial cell with different concentration of drugs to perform dose inhibition studies. We found that the antimetabolites inhibited the proliferation of rabbit retinal pigment epithelial cell in a dose dependent and a time dependent manner. The drug concentration required for 50% inhibition of cell growth (ID50) were found to be as follows (BCNU; 6.51 mg/L, 5-FU ; 8.94 mg/L, Daunorubicin; 0.03mg/L, Mitomycin-C; 0.26mg/L).
Antimetabolites* ; Daunorubicin ; Epithelial Cells* ; Fluorouracil ; Mitomycin ; Retinaldehyde* ; Vitreoretinopathy, Proliferative

Late bleb leak after trabeculectomy is a serious and intractable complication and its frequency is increasing as antimetabolites are used in the surgery. Various modalities have been challenged in the treatment of late bleb leak but the results have not been satisfactory.Amniotic membrane is avascular tissue with thick basement membrane and rich stroma, and it can modulate wound.As it does not express HLA, it doesn t induce graft rejection. With the use of these characteristics of amniotic membrane, we report a case in which late bleb leak after trabeculectomy with MMC was successfully treated with amniotic membrane transplantation maintaining bleb function.
Amnion* ; Antimetabolites ; Basement Membrane ; Blister* ; Graft Rejection ; Humans* ; Membranes ; Trabeculectomy

PURPOSE: The purpose of this study was to evaluate the effects of revision endoscopic endonasal dacryocystorhinostomy (EDCR) and the causes of postoperative failure after primary endoscopic DCR in patients with nasolacrimal duct obstruction. METHODS: This prospective study enrolled 32 patients (32 eyes) who had undergone revision of endoscopic DCR with the diagnosis of obstruction of nasolacrimal system after primary EDCR between October 1997 and February 2003. RESULTS: The most common cause of revision operation after primary EDCR was granuloma, followed by membranous obstruction and common canalicular obstruction. The success rate of the cases with granuloma was 69.2%, and that with membranous obstruction was 100%. CONCLUSIONS: Revision EDCR success rate can be improved by reducing the frequency of granuloma as this was the most common factor for revision EDCR. The effect of antimetabolites in revision EDCR success rate is to be further evaluated.
Antimetabolites ; Dacryocystorhinostomy ; Diagnosis ; Granuloma ; Humans ; Nasolacrimal Duct ; Prospective Studies

Radiotherapy has been offered to patients with pancreatic cancer, either in the adjuvant or definitive setting. However, the role of radiotherapy in pancreatic cancer is increasingly doubted, especially after the introduction of gemcitabine to both domains. Although contradictory data exist, combined chemoradiotherapy improves both quantity and quality of life for patients with locally advanced tumors compared with radiotherapy alone or chemotherapy alone. Recently, induction chemotherapy strategy is being evaluated for better selection of patients for optimal benefit from consolidative chemoradiotherapy. Much controversy has been suggested concerning the role of adjuvant radiotherapy, but quality assurance for radiotherapy was not considered in the previously reported studies. Combined chemoradiotherapy in the adjuvant setting is still considered as a viable option. Current phase III randomized on-going studies will provide better answers on the role of radiotherapy in the treatment of pancreatic cancer.
Antimetabolites/therapeutic use ; Antimetabolites, Antineoplastic/therapeutic use ; Combined Modality Therapy ; Deoxycytidine/analogs & derivatives/therapeutic use ; Fluorouracil/therapeutic use ; Humans ; Pancreatic Neoplasms/drug therapy/*radiotherapy

Antimetabolites, 5-fluorouracil(5-FU) and mitomycin-C(MMC), are used to promote the success rate of the glaucoma filtration surgery(GFS). The authors observed and compared the duration of bleb formation and complications by slit-lamp biomicroscopy, and the inhibition of fibroblast proliferation and of fibrosis by light microscopy following GFS in 4 group rabbits. One hundred and twenty rabbits comprised in this study were divided into four groups; the first control group(I) was the balanced salt solution soaked group(BSS) during GFS, the second(II) was the 5-FU subconjunctival injected group(5-FU SC) after GFS, the third(III) was the 5-FU soaked group(5-FU) during GFS, and the fourth(IV) was the MMC soaked group(MMC) during GFS. For the maintenance of bleb formation, MMC, 5-FU SC, 5-FU and BSS group showed 0%, 26.7%, 16.7%, 100% at the 1 month after GFS, and 0%, 0%, 0%, 73.3% at the 2 months after GFS, respectively, which suggested that MMC group lasted longest. The inhibition of fibrosis and fibroblast proliferation became higher in the order of MMC, 5-FU, 5-FU SC, BSS group at 2 weeks after the surgery. At 3 months after GFS, there was no conspicuous statistic difference(P>0.05) between 5-FU SC and 5-FU group, but some differences(P<0.001) in the rest groups. From these results, we concluded that antimetabolites such as 5-FU and MMC could be used effectively in cases of poor prognosis of GFS. However, the dosage and application method of antimetabolites should be considered very carefully and further research will be necessary to find out the optimal dosage with minimum toxicity.
Antimetabolites ; Blister ; Fibroblasts ; Fibrosis ; Filtering Surgery* ; Filtration* ; Fluorouracil* ; Glaucoma* ; Microscopy ; Mitomycin* ; Prognosis ; Rabbits*

PURPOSE: To investigate the effects of two antimetabolites, mitomycin C (MMC) and 5-fluorouracil (5-FU), on proliferation of cultured human nasal mucosa fibroblasts. METHODS: Human nasal mucosa fibroblasts were primarily cultured, and exposed to various concentrations of MMC and 5-FU for 5 minutes. Control fibroblasts were exposed to only DMEM media without the drugs. Effect of drugs on cell morphology was observed by phase-contrast microscopy. Cell viability and apoptosis were measured using MTT [3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl-tetrazolium bromide] assay and Acridine orange/Hoechst (AO/HO) staining, respectively. RESULTS: In both experimental groups exposed to MMC and 5-FU, fibroblasts maintained standard spindle shape. The MTT assay showed that both MMC and 5-FU inhibited fibroblast proliferation in a dose dependent manner. AO/HO staining showed apoptotic cells in both experimental groups. CONCLUSIONS: Both MMC and 5-FU have an antiproliferative effect on fibroblasts in vitro at least through induction of apoptosis. Therefore, adjuvant use of either MMC or 5-FU during endonasal dacryocystorhinostomy may improve the clinical outcome by inhibiting proliferation of the nasal mucosa.
Antimetabolites ; Apoptosis ; Cell Survival ; Dacryocystorhinostomy ; Fibroblasts ; Fluorouracil ; Humans ; Microscopy, Phase-Contrast ; Mitomycin ; Nasal Mucosa

The authors investigated the toxicity of two antimetabolites. 5-fluorouracil(5-FU) and mitomycin-C(MMC) on the rabbit cornea and sclera following glaucoma filtration surgery(GFS). Forty rabbits were divided into four groups; the first control group(I) was the balanced salt solution soaked group(BSS) during GFS, the second(II) was the 5-FU subconjunctival injected group(5-FU SC) after GFS, the third(III) was the 5-FU soaked group(5-FU) during GFS, and the fourth(IV) was the MMC soaked group(MMC) during GFS. At the fifth day after GFS, scanning electron microscopic findings showed that corneal epithelial cells were most seriously damaged in 5-FU SC group, slightly damaged in 5-FU group, and no change in MMC and BSS group. At six months after GFS, transmission electron microscopic observation on sclera revealed the most profound degenerative changes in 5-FU group, and followed by an order of MMC, 5-FU SC, and BSS group. These results suggest that the dosage and application method of antimetabolites should be selected with great caution to prevent ocular toxicity.
Antimetabolites ; Cornea* ; Epithelial Cells ; Filtering Surgery* ; Filtration* ; Fluorouracil* ; Glaucoma* ; Mitomycin* ; Rabbits ; Sclera*

Antimetabolites that inhibit postoperative fibroblast proliferation increases the success of glaucoma filtration surgery. However, the use of mitomycin C in young patients has not been extensively studied. The effectiveness of initialtrabeculectomy with mitomycin C or uncomplicated glaucoma in patients age 40 years or younger was evaluated in a consecutive series of 15 eyes of 10 patients. Thirteen eyes had juvenile primary open-angle glaucoma and 2 eyes had steroid induced glaucoma. Mitomycin C (0.002%) was applied for 2 to 4 minutes during the surgery. The success rate was evaluated with Kaplan-Meier analysis, and it was 78% at postoperative 9 months. Complications included postoperative hyphema(7 eyes), hypotony (2 eyes), and bleb-related endophthalmitis.
Antimetabolites ; Endophthalmitis ; Fibroblasts ; Filtering Surgery ; Glaucoma ; Glaucoma, Open-Angle ; Humans ; Kaplan-Meier Estimate ; Mitomycin* ; Trabeculectomy*