Application of 5-fluorouracil and bandage contact lens in pterygium excision combined with autogenous limbal stem cell transplantation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To assess the clinical efficacy of 5-fluorouracil(5-FU)and bandage contact lens in the pterygium excision combined with autogenous limbal stem cell transplantation(ALSCT)in treating patients with pterygium.METHODS:Random controlled clinical trial. A total of 71 patients(71 eyes)of pterygium who treated at the department of ophthalmology in Qinhuangdao Haigang Hospital between May 2021 and November 2022 were included. They were divide into three groups, including 23 eyes received pterygium excision combined with ALSCT in group A, 24 eyes that were administered with 5-FU intraoperatively and postoperatively in group B, and 24 eyes that received both bandage contact lens and 5-FU in group C. Furthermore, comfort levels at 1, 3, 7, 14d postoperatively, corneal epithelial healing at 1, 3, 7, 14d and 1mo postoperatively, treatment outcomes and complications at 3～6mo postoperatively were compared among the three groups of patients.RESULTS:The comfort levels at 1, 3 and 7d postoperatively and corneal healing at 1 and 3d postoperatively of the group C were better than those of the groups A and B. There were no statistical significant differences in the comfort levels at 14d after surgery and corneal healing at 14d and 1mo after surgery among the three groups of patients. Over a 3～6mo follow-up period, group A experienced recurrence in 3 eyes, group B had 1 recurrence, while group C had no recurrence. There were no statistically significant differences in complication rates among the three groups of patients.CONCLUSIONS: The application of 5-FU combined with bandage contact lens can enhance postoperative comfort levels, promote corneal epithelial healing, and improve the success rate in pterygium excision combined with ALSCT.

Effect of Fuzheng Jiedu Prescription Combined with 5-Fu Against Postoperative Recurrence and Metastasis of Gastric Cancer in Mice： An Exploration Based on Endoplasmic Reticulum Stress / 中国实验方剂学杂志

Objective:To investigate the inhibitory effect of Fuzheng Jiedu prescription（FZJDP） combined with 5-fluorouracil （5-Fu） against postoperative recurrence and metastasis in gastric cancer-bearing mice and explore the possible mechanism based on changes in CD4⁺ T cells， CD8⁺ T cells， and regulatory T （Treg） cells of tumor microenvironment， endoplasmic reticulum stress （ERS） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B（Akt）/mammalian target of rapamycin（mTOR） pathway. Method:Forty 615 mice were randomly divided into the model group，FZJDP （25 g·kg^-1） group，5-Fu（25 mg·kg^-1）group，and combined （25 g·kg^-1 FZJDP + 25 mg·kg^-1 5-Fu）group， with 10 mice in each group. Mouse forestomach carcinoma （MFC） cells were implanted into the inner side of footpad of the left hind paw and the transplanted tumor was then surgically excised to establish a postoperative recurrence model. Hematoxylin-eosin（HE） staining was conducted to observe the pathological changes in mice with gastric cancer recurrence and lung metastasis. The CD4⁺/CD8⁺ T cell ratio in recurrent tumor and the percentages of Treg cells ［CD4⁺，CD25⁺， and forkhead box protein P3 （FOXP3）⁺ cells］ in spleen were detected by flow cytometry. The contents of ERS-related proteins ［78-kDa glucose-regulated protein（GRP78），inositol-requiring enzyme 1 alpha （IRE1<italic>α</italic>），activating transcription factor 6（ATF6），and protein kinase R-like endoplasmic reticulum kinase（PERK）］ and the expression of related proteins in the PI3K/Akt/mTOR signaling pathway were determined by Western blot and immunohistochemistry （IHC）. Result:Compared with the model group， the combined group significantly increased the recurrent inhibition rate （<italic>P</italic><0.05）. The recurrent tumor weight was significantly decreased in each treatment group （<italic>P</italic><0.05）. The number of lung metastases and metastasis rate declined in each treatment group， and the lowest values were observed in the combined group， without any statistical significance. The CD4⁺/CD8⁺ T cell ratios in the FZJDP group and combined group were significantly elevated （<italic>P</italic><0.05）， while the percentages of Treg cells were reduced （<italic>P</italic><0.05）. However， 5-Fu resulted in a significant increase in Treg cell percentage （<italic>P</italic><0.05）. IHC results showed that the protein expression levels of ATF6 （<italic>P</italic><0.05，<italic>P</italic><0.01）， IRE1<italic>α</italic>（<italic>P</italic><0.05），and Akt （<italic>P</italic><0.01） in each treatment group were significantly down-regulated as compared with those in the model group. As revealed by Western blot， the GRP78 expression level in the 5-Fu group was lower than that in the model group （<italic>P</italic><0.05）， and the expression levels of PI3K， phosphorylated Akt （p-Akt）， and mTOR were significantly decreased in the 5-Fu group and the combined group （<italic>P</italic><0.05）. Conclusion:FZJDP combined with 5-Fu reduces postoperative recurrence and metastasis in tumor-bearing mice possibly by inhibiting PI3K/Akt/mTOR signaling pathway， diminishing ERS，and improving tumor immune microenvironment.

Curcumin mediates IL-6/STAT3 signaling pathway to repair intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer / 中国中药杂志

This study aims to investigate the potential mechanism of curcumin in mediating interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3) signaling pathway to repair intestinal mucosal injury induced by 5-fluorouracil(5-FU) chemotherapy for colon cancer. SD rats were intraperitoneally injected with 60 mg·kg~(-1)·d~(-1) 5-FU for 4 days to establish a model of intestinal mucosal injury. Then the rats were randomly divided into model group(equal volume of normal saline), curcumin low, medium and high dose groups(50, 100, 200 mg·kg~(-1)), and normal SD rats were used as control group(equal volume of normal saline). Each group received gavage administration for 4 consecutive days, and the changes of body weight and feces were recorded every day. After administration, blood was collected from the heart, and jejunum tissues were collected. The levels of serum interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA, and at the same time, the concentration of Evans blue(EB) in jejunum was measured. Hematoxylin-eosin(HE) staining was used to observe the pathological state of jejunum, and the length of jejunum villi and the depth of crypt were measured. The positive expression levels of claudin, occludin and ZO-1 were detected by immunohistochemistry. Western blot was used to detect the protein expression of IL-6, p-STAT3, E-cadherin, vimentin and N-cadherin in jejunum tissues. The results showed that, curcumin significantly increased body weight and fecal weight(P<0.05 or P<0.01), decreased fecal score, EB concentration, IL-1β and TNF-α levels(P<0.05 or P<0.01) in rats. In addition, curcumin maintained the integrity of mucosal surface and villi structure of jejunum to a large extent, and reduced pathological changes in a dose-dependent manner. Meanwhile, curcumin could increase the positive expression of occludin, claudin and ZO-1(P<0.05 or P<0.01), repair intestinal barrier function, downregulate the protein expression of IL-6, p-STAT3, vimentin and N-cadherin in jejunum tissues(P<0.05 or P<0.01), and upregulate the protein expression of E-cadherin(P<0.05). Therefore, curcumin could repair the intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer, and the mechanism may be related to the inhibition of IL-6/STAT3 signal and the inhibition of epithelial-mesenchymal transition(EMT) process.

Effect of DUOX2 on sensitivity of colorectal cancer cells to 5-fluorouracil / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effect of double oxidase 2 (DUOX2) on the sensitivity of colorectal cancer (CRC) cells to 5-fluorouracil (5-FU). Methods: CRC cell lines DLD-1, SW480, HCT116, SW620 and normal intestinal epithelial cell line NCM460 were selected, and the expression of DUOX2 in these cell lines were detected by qPCR. DUOX2 expression in HT-29 and HCT116 cells was stably knocked down by lentivirus infection technique. The knockdown efficiency was detected by qPCR and WB. Cells in sh-Control and sh-DUOX2 groups were treated with 5-FU at different concentrations (0, 5, 10, 20, 40, 80, 120 μg/ml). The effects of 5-FU on cell proliferation, apoptosis and cell cycle were detected by CCK-8 method and flow cytometry. HT29 cell transplanted xenograft model in nude mice was constructed to observe the effect of DUOX2 gene on the treatment efficacy of 5-FU. Results: the expression level of DUOX2 mRNA in CRC cells was significantly higher than that in NCM460 cells (P<0.05 or P<0.01). Compared with sh-Control group, the mRNA and protein expressions of DUOX2 in sh-DUOX2 group were significantly decreased (all P<0.01); the sensitivity of cells to 5-FU was enhanced, the apoptosis rate and the ratio of cells at G0/G1 phase were significantly increased (all P<0.01), and the ratio of cells at G2 and S phase was significantly decreased (all P<0.01). There was no significant difference in tumor volume and mass between sh-Control group and sh-DUOX2 group without 5-FU treatment (all P>0.05), but the volume and mass of transplanted tumor in sh-DUOX2+5-FU group after 5-FU treatment was significantly lower than that in sh-Control+5-FU group (all P<0.01). Conclusion: The sensitivity of CRC cells to 5-FU can be significantly enhanced by knocking down DUOX2 gene.

Effect and molecular mechanism of Lin28 on 5-Fu sensitivity of hepatocellular carcinoma HepG2 cells / 中国肿瘤生物治疗杂志

@# Objective: To investigate the effect and mechanism of RNA binding protein Lin28 on the 5-fluorouracil (5-Fu) sensitivity of HepG2 cells. Methods: HepG2 cells were transfected with plasmid pcDNA3.1-Lin28 or si-Lin28 (small interfering RNA of Lin28). qPCR and Western blotting were used to detect the expression of Lin28 in HepG2 cells after transfection. Changes of cell proliferation in transfected cells after 5-Fu treatment was detected by CCK8 assay and the 50% inhibitory concentration (IC50) was calculated. Flow cytometry was used to detect apoptotic rate after 5-Fu treatment and the expression of apoptosis-related protein was assayed by Western blotting. The mRNA expressions of drug-resistant miRNAs (let-7a and let-7b), as well as cancer stem cell markers (Oct4, Nanog and Sox2) after transfection were detected by qPCR. Results: As compared to the HepG2/Vector cells, the mRNA and protein expressions of Lin28 were significantly up-regulated in HepG2/Lin28 cells (P<0.05 or P<0.01). Over-expression of Lin28 significantly suppressed the sensitivity of HepG2 cells to 5-Fu (IC50elevated obviously, P<0.05) and significantly increased cell proliferation while decreased apoptotic rate and expression of apoptotic-related protein caspase-3 (all P<0.01). As compared to si-control group, expression of Lin28 in HepG2/si-Lin28 cells was significantly down-regulated (P<0.01). Lin28 knockdown significantly reduced cell proliferation and IC50 of 5-Fu (all P<0.01) but increased apoptotic rate and expression of apoptosis-related protein (P<0.01). Compared with HepG2/Vector group, expressions of let-7a and let-7b, as well as cancer stem cell markers (Oct4, Nanog and Sox2) were significantly increased in HepG2/Lin28 cells (all P<0.01); while these molecules were significantly decreased in HepG2/si-Lin28 cells as comparing to si-control group (all P<0.01). Conclusion: Lin28 can modulate the chemosensitivity of HepG2 cells by regulating the expression of miRNAs and the formation of cancer stem cells. Targeting Lin28 might be a promising approach to improve the chemotherapy efficacy in HCC.

Study on synergistic anti-tumor effect of Shuangdan Capsules combined with 5-FU on hepatocellular carcinoma cells Huh-7 and xenograft mice / 中国中药杂志

This paper discussed the synergistic anti-tumor effect of Shuangdan Capsules combined with 5-fluorouracil(5-FU) on human liver cancer cell line Huh-7 and tumor bearing mice. The effects of Shuangdan Capsules combined with 5-FU on the activity and vascular endothelial growth factor(VEGF) receptor protein expression of Huh-7 cells were investigated, and the effects of drug combination on tube formation of HUVEC cell were also verified. In addition, the mice model of Huh-7 was established to observe the anti-tumor effect of drug combination and the distribution of tumor blood flow in tumor bearing mice by using molecular imaging. HPLC analysis showed that Shuangdan Capsules mainly consisted of danshensusodium, protocatechuic aldehyde, paeoniflorin, rosmarinic acid, alkannic acid, salvianolic acid B, and paeonol. In MTT experiment, the inhibition rate of Shuangdan Capsules(20 mg·L~(-1)) and 5-FU(1 μmol·L~(-1)) on Huh-7 cells was 60%, and the CI value was 0.59, suggesting that these two drugs had synergistic anti-hepatoma cells effect. The expression of VEGF receptor in Huh-7 cells was inhibited by the combination of these two drugs. In addition, the process of HUVEC was slow, and the number, length and area of the lumen branches decreased significantly. In vivo, Shuangdan Capsules combined with 5-FU inhibited the growth and prolongation of survival of Huh-7 cells in subcutaneous transplanted tumor nude mice; serum expression of CD31 and VEGF in nude mice were decreased, while caspase-3 was increased. Meanwhile, the drug combination significantly inhibited the expressions of MMP2 and VEGF in tumor tissues. Ultrasound showed that Shuangdan Capsules combined with 5-FU also inhibited tumor angiogenesis and reduced blood flow of tumor tissue. The results showed that Shuangdan Capsules combined with 5-FU may inhibit tumor angiogenesis by inhibiting VEGF and MMP2 expressions, thereby blocking tumor growth.

Effect of Yiqi Jianpi Huayu Recipe Combined with 5-FU on Growth and Immune Function of Subcutaneous Transplanted Tumor in MFC Bearing Mice / 中国实验方剂学杂志

Objective:To discuss the effect of Yiqi Jianpi Huayu recipe (YQJPHY) combined with 5-fluorouracil(5-FU) on the growth and immune function of subcutaneous transplanted tumor in MFC tumor bearing 615 mice. Method:Twenty-four mice were inoculated subcutaneously to establish the transplanted tumor model of gastric cancer in mice, and then randomly divided into model control group, YQJPHY (20 g·kg-1)group, 5-FU (25 mg·kg-1) group and (YQJPHY+5-FU) combined group, with 6 rats in each group. After the last administration, the transplanted tumor, spleen and thymus were stripped completely. The tumor inhibition rate, thymus and spleen index were calculated. Flow cytometry was used to determine the content of myeloid-derived suppressor cells (MDSCs) and its subtype polykaryotype cells (PMN-MDSC), single karyotype cells (M-MDSC) in both peripheral blood and tumor tissue, and macrophages and their M1 type, M2 type, T lymphocyte, B lymphocyte, and natural killer cells (NK cells) in peripheral blood. Expressions of arginase-1(Arg-1) and inducible nitric oxide synthesis (iNOS) gene in tumor tissues were detected by Real-time PCR. Result:Compared with model control group, the weight of mice in YQJPHY group increased, whereas the weight of tumor, the weight of tumor, the index of thymus and spleen decreased in 5-FU group(PPPPPPPP+,CD4+,CD8+ T cell group decreased(PPPPPPConclusion:YQJPHY can better inhibit the growth of subcutaneous transplanted tumor when combined with 5-FU, and improve immune status after chemotherapy. The mechanism may be related to the decrease of MDSCs content and the increase of T cell and macrophages content.

Sensitization of 5-Fluorouracil-Resistant SNUC5 Colon Cancer Cells to Apoptosis by α-Mangostin

5-fluorouracil (5-FU) is a chemotherapeutic agent commonly used for treatment of solid tumors, including colorectal cancer. However, chemoresistance against 5-fluorouracil (5-FU) often limits its success for chemotherapy and, therefore, finding out appropriate adjuvant(s) that might overcome chemoresistance against 5-FU bears a significant importance. In the present study, we have found that α-mangostin can sensitize 5-FU-resistant SNUC5/5-FUR colon cancer cells to apoptosis. Exposure of α-mangostin induced significant DNA damages and increased the intracellular 8-hydroxyguanosine (8-OH-G) and 4-hydroxynonenal (4-HNE) levels in SNUC5 and SNUC5/5-FUR cells. Western blot analysis illustrated that α-mangostin-induced apoptosis was mediated by the activation of the extrinsic and intrinsic pathways in SNUC5/5-FUR cells. In particular, we observed that Fas receptor (FasR) level was lower in SNUC5/5-FUR cells, compared with SNUC5 cells and that silencing FasR attenuated α-mangostin-mediated apoptosis in SNUC5/5-FUR cells. Together, our study illustrates that α-mangostin might be an efficient apoptosis sensitizer that can overcome chemoresistance against 5-FU by activating apoptosis pathway.

Effects of sphingosine kinase 1 inhibitors in combination with 5-FU on gastric cancer MGC-803 cells and the possible mechanisms / 西安交通大学学报(医学版)

Objective To investigate the effects of sphingosine kinase 1 (SphK1 ) inhibitor N, N-dimethylsphingosine (DMS)combined with 5-fluorouracil (5-FU)on the proliferation and apoptosis of gastric cancer MGC-803 cells and to explore the possible mechanisms involved.Methods MGC-803 cells were cultured in vitro.The effects of DMS and 5-FU on cell proliferation,apoptosis,and cell cycle distribution of MGC-803 cells were detected by MTT assay and flow cytometer (FCM),respectively.The expressions of SphK1 ,TS,DPD,NF-κB p65 and Bcl-2 proteins were detected by Western blot.Results Different concentrations of DMS or 5-FU alone or in combination could obviously inhibit the proliferation of MGC-803 cells in a dose-dependent and time-dependent manners (P0.05).As compared with the cells without drug treatment,DMS or 5-FU alone could obviously increase the apoptosis rate of MGC-803 cells (P<0.05);the apoptosis rate in the combination group was significantly higher than that in the single-drug groups (P<0.05).The expression levels of SphK1,NF-κB p65 and bcl-2 proteins were down-regulated with the treatment of DMS alone or in combination,whereas those of TS and DPD were not affected.Conclusion DMS can inhibit the proliferation and induce apoptosis of gastric cancer MGC-803 cells in vitro.It shows a good synergetic effect in combination with 5-FU,probably by down-regulating the expressions of SphK1,NF-κB p65 and Bcl-2 proteins.

A Case of Corneal Endothelial Damage by 5-Fluorouracil Inflow Into Anterior Chamber After Subconjunctival Injection

PURPOSE: To present a case of corneal endothelial damage caused by inflow of 5-FU after subconjunctival 5-FU injection in a patient undergoing trabeculectomy. CASE SUMMARY: A 65-year-old female patient diagnosed with chronic angle-closure glaucoma underwent trabeculectomy using mitomycin C. Three weeks after the surgery, her intraocular pressure (IOP) elevated, and the follicles had disappeared by trabeculectomy. Subsequently, subconjunctival 5-FU injection was performed. Following the fourth injection, visual acuity abruptly decreased, and corneal edema was observed. Upon presumption of inflow of 5-FU into the anterior chamber, anterior chamber irrigation was performed within 40 minutes. On postoperative day 1, visual acuity decreased from 0.8 to counting fingers, and diffuse corneal edema and anterior capsular opacity of the lens were noted. Three months after the irrigation, visual acuity improved to 0.8. Corneal edema and capsular opacity also improved, however the density of the corneal endothelial count decreased. CONCLUSIONS: Inflow of 5-FU into the anterior chamber can cause corneal and lenticular toxicity. Anterior chamber irrigation is considered necessary to prevent 5-FU toxicity.

A case of microinvasive Paget's disease of the vulva: Treatment of positive resection margin with topical 5-FU cream application / 대한산부인과학회지

Extramammary Paget's disease of the vulva is a rare lesion that accounts for 1~2% of vulvar neoplasms. Paget's disease often has a microscopic extension beyond the gross lesion and shows a multifocal distribution. Positive resection margin is common. We applied 5-FU cream on the lesion who had a positive resection margin. There was no residual lesion on multiple punch biopsies after 5-FU cream treatment three months later. And there has been no evidence of disease recurrence in the 12-month follow-up period. We experienced a case of effective treatment with 5-FU cream in microinvasive Paget's disease of the vulva with positive resection margin. We present it with a brief review of literatures.

Inhibitory effect of 5-fluorouracil encapsulated by galactosylceramide liposomes on drug resistance and its mechanisms / 中国药理学通报

Aim To study inhibitory effect of 5-fluorouracil encapsulated by galactosylceramide liposomes (5-Fu-GCL)on 5-Fu-resistent HepG_2 cells and its mechanisms. Methods Inhibitory effect of 5-Fu-GCL on established model of 5-Fu-resistant HepG_2 cells was assessed with MTT assay in vitro. The concentration-time course of 5-Fu-GCL in intracellular fluid was detected with high performance liquid chromatography (HPLC). Thymidylic acid synthase (TS) expression was observed with immunohistochemical method,and NO content was determined with chemical method. Results Obvious inhibitory effects of 5-Fu-GCL (75,150,300,600,1200?mol?L-1) on 5-Fu-resistant HepG_2 cells were observed with IC_ 50 of 158.6 ?mol?L-1,far lower than that of free 5-Fu (400.9 ?mol?L-1). 5-Fu-GCL (300 ?mol?L-1) inhibited 5-Fu-resistant HepG_2 cells in a time-dependent manner,and the inhibitory effect of 5-Fu-GCL was stronger than that of free 5-Fu during 12～48 h. Compared with free 5-Fu,5-Fu-GCL (300 ?mol?L-1) increased the content of intracellular fluid in 5-Fu-resistant HepG_2 cells. 5-Fu-GCL(62.5,300,1200 ?mol?L-1) not only inhibited the expression of TS,but also increased the production of NO in 5-Fu-resistant HepG_2 cells,and these effects of 5-Fu-GCL(300,1200 ?mol?L-1) were stronger than those of free 5-Fu. Conclusion 5-Fu-GCL has inhibitory effect on 5-Fu-resistant HepG_2 cells. The effect may be related to the increased concentration of 5-Fu-GCL in intracellular fluid,inhibited expression of TS and increased production of NO.

The Toxic and Morphologic Effects of Mitomycin-C, 5-FU and Genistein on Rabbit Corneal Endothelium

PURPOSE: We determined the toxic and morphologic effects of the anti-proliferative drugs, mitomycin-C (MMC), 5-fluorouracil (5-FU) and genistein on rabbit corneal endothelium. METHODS: After intramuscular anesthesia, each drug of different concentrations (MMC at 0.05, 0.1, and 0.2 mg/ml; 5-FU at 5, 10, and 50 mg/ml; and genistein at 0.013, 0.027, and 0.054 mg/ml) was perfused into the anterior chamber of 54 white rabbits (108 eyes). The same amount of balanced salt solution was perfused into control eyes. The corneal thickness was measured before perfusion and 15 min, 30 min, 45 min, 1 h, and 24 h after perfusion. Corneal samples were prepared at 24 h after perfusion to determine the changes in corneal thickness and to observe morphologic changes of corneal endothelium under scanning electron microscope (SEM). RESULTS: A significant increase in corneal thickness was observed. Destruction of corneal endothelial cell structure was seen under scanning electron microscope at 24 h after perfusion with MMC at 0.2 mg/ml for 1, 3, and 5 min, and at 0.1 mg/ml for 5 min; and 5-FU at 50 mg/ml for 5 min into the anterior chamber. However, no significant difference was seen in corneal thickness or in corneal endothelial morphology at 24 h after perfusion with genistein. CONCLUSIONS: To avoid morphologic changes of the cornea, we recommend the anterior chamber perfusion of MMC at 0.1 mg/ml between 1 and 2 min, 5-FU at 10 mg/ml between 3 and 5 min, and genistein at 0.027 mg/ml for 5 min. Genistein at low concentrations showed no morphologic change in the cornea, suggesting the possible clinical use with safety.

The Effect of 5-Fluorouracil or Mitomycin-C in Glaucoma Filtration Surgery on the Rabbit Cornea and Sclera

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.

Trabeculectomy and the use of Low-dose 5-Fluorouracil

5-Fluorouacil (5-FU) 5mg/day was injected subconjunctivally from the third day after trabeculectomy in 8 eyes of 7 patients who had poor prognostic glaucomas such as previously unsuccessful trabeculectomy, aphakic glaucoma, glaucoma after retinal reattachment surgery, and inflammatory glaucoma. The eyes were injected once or multiple times no more than eigth doses in total. Each dose contained 5 mg of 5-FU so patients were given a minimum dosage of 5 mg or an additive maximum dosage of 40 mg. The follow-up period ranged from 2 months to 9 months and averaged 6 months. All eyes showed intraocular pressure below 21 mmHg with or without anti glaucoma medications with the mean intraocular pressure reduced by 16.5 +/- 9.4mmHg from 30.8mmHg preoperatively to 14.3mmHg postoperatively. The postoperative visual acuity was decreased in one eye and remained unchanged in 7 eyes. Diffuse filtering blebs were seen in 7 eyes and an encapsulated bleb was encountered in one eye. The average number of antiglaucoma medications was decreased from 3 preoperativdy to 1.4 postoperatively. Postoperative complications were corneal epithelial detect and conjunctival wound leak in one eye and conjunctival wound leaks alone in two other eyes.

Low-dose 5-Fluorouracil and Glaucoma Filtering Surgery

It has been known that subconjunctival injections of 5-fluorouracil (5-FU) may enhance the surgical outcome of glaucomatous eyes with poor prognosis after filtering surgery. The authors reviewed 24 eyes of 23 patients who had received subconjunctival injections of 5-FU after filtering surgery, and all of them were followed up at least 6 months. The average follow-up period was 12 months, and the average total dosage of 5-FU was 17.4mg per eye. Successful surgical outcomes were observed in 7 of 10 eyes with glaucoma after unsuccessful filtering surgery (70%), 7 of 9 eyes with neovascular glaucoma (78%), and 4 of 5 eyes with aphakic glaucoma (80%). The complications of filtering surgery and 5-FU injections were corneal epithelial defects (17%), hyphema (12%), conjunctival wound leakage (4%), and filtering site obstruction (4%). Therefore, we think that postoperative subconjuntival 5-FU injection increase the success rate of filtering surgery in refractory glaucoma.