Hypoxia, a state of low oxygen, is a common feature of solid tumors and is associated with disease progression as well as resistance to radiotherapy and certain chemotherapeutic drugs. Hypoxic regions in tumors, therefore, represent attractive targets for cancer therapy. To date, five distinct classes of bioreactive prodrugs have been developed to target hypoxic cells in solid tumors. These hypoxia-activated prodrugs, including nitro compounds, N-oxides, quinones, and metal complexes, generally share a common mechanism of activation whereby they are reduced by intracellular oxidoreductases in an oxygen-sensitive manner to form cytotoxins. Several examples including PR-104, TH-302, and EO9 are currently undergoing phase II and phase III clinical evaluation. In this review, we discuss the nature of tumor hypoxia as a therapeutic target, focusing on the development of bioreductive prodrugs. We also describe the current knowledge of how each prodrug class is activated and detail the clinical progress of leading examples.
Anthraquinones ; chemistry ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; Aziridines ; chemistry ; pharmacology ; Cell Hypoxia ; drug effects ; Humans ; Indolequinones ; chemistry ; pharmacology ; Molecular Structure ; NAD(P)H Dehydrogenase (Quinone) ; chemistry ; pharmacology ; Neoplasms ; drug therapy ; pathology ; Nitrogen Mustard Compounds ; chemistry ; pharmacology ; Nitroimidazoles ; chemistry ; pharmacology ; Phosphoramide Mustards ; chemistry ; pharmacology ; Prodrugs ; chemistry ; pharmacology ; Triazines ; chemistry ; pharmacology

Purpose: To prevent the occurrence of secondary cataract after ECCE with PC-IOL implantation and evaluate the safety and effectiveness of Mitomycin C and 5-FU when used intraocular as an irrigating solution for its prevention in rabbits Materials and Methods: 15 rabbits were divided into 3 groups: Group A was given 5-50 mg/ml FU in 500 cc of BSS plus solution; Group B received MMC 0.2 percent mg/ml in 500 cc BSS; and Group C served as control with pure BSS. The study was done in accordance with the guidelines published by ARVO. The investigated drug solution was used as irrigating solution in cataract extraction performed in rabbits. Postoperatively, the rabbits examined under slit lamp from the 1st post op day and every 3 days thereafter. Their globes were enucleated 2 wks post op and 4 weeks post op, and sent to Pathology Laboratory for processing Results: Group A and Group B showed clear posterior capsule with no evidence of epithelial cell migration. Group C showed evidence of minimal to moderate epithelial cell migration and proliferation with fibrosis Conclusion: Mitomycin C (MMC) and 5-FU minimized and even prevented secondary cataract formation, with no effect on ocular structures when used as an irrigating solution.
Animal ; MITOMYCIN ; MITOMYCIN C ; MITOMYCINS

CLINICAL SCENARIO A 30-year-old overseas contract worker consulted the outpatient department for a noninflamed, large, slightly vascularized, fleshy mass that encroached on the limbus of the right eye and reached the paracentral area of the cornea. The mass gradually increased in size over the past 3 years, associated with occasional redness that spontaneously resolved without any medication. The vision in the right eye degenerated over the last year. There were no other ocular or systemic signs and symptoms, and no surgery was ever done in that eye. Visual acuity was 20/40 (correctable to 20/20) in the right eye (OD) and 20/20 uncorrected in the left eye (OS). Manifest refraction revealed an against the-rule astigmatism of -2.0 diopters OD and plano OS. The rest of the ophthalmic examination was normal. His agency instructed him to have the mass removed prior to departure for Dubai in about 4 months. Since the mass was already causing astigmatism and reduced uncorrected visual acuity, surgery was contemplated. The ophthalmologist on duty wants to know whether the traditional bare-sclera technique is still the best method to use in treating this disease and preventing recurrence CLINICAL QUESTION: Pertinent data presented include a noninflamed, fleshy mass that over a period of 3 years gradually crossed the limbal border into the paracentral area of the cornea causing a two-diopter against-the-rule astigmatism. In the absence of any previous eye surgery, this picture is compatible with a primary pterygium After identifying the ocular condition in the clinical scenario, a clinical question can now be formulated as follows: Among patients with primary pterygia, how effective is bare-sclera technique compared to adjuvant treatment with mitomycin C (MMC) or conjunctival autografting (CA) in minimizing pterygium recurrence? (Author)
MITOMYCIN

No abstract available.
Constriction, Pathologic* ; Dilatation* ; Mitomycin*

The purpose of this study is to compare the effects of three different concentrations of mitomycin-C(MMC) as an adjunct therapy to trabeculectomy. We reviewed 26 patients(36 eyes) who underwent trabeculectomy in which MMC was applied intraoperatively. The application time was 5 minute, and concentration of MMC was 0.1mg/ml(n=10), 0.2mg/ml(n=17) and 0.41mg/ml(n=9) respectively. The mean IOP at postoperative 3 months was significantly lower in 0.4mg/ml group (10.4 +/- 5.5mmHg) than in the 0.2mg/ml group(16.1 +/- 4.7mmHg)(p<0.05). There was no statistical difference among the three groups in the success rate regardless of medication, the size and longevity of bleb. The postoperative hypotony(2 eyes) was noted in the 0.4mg/ml group. In conclusions, It is desirable to use the lowest concentration of MMC that will facilitate bleb formation.
Blister ; Longevity ; Mitomycin* ; Trabeculectomy*

The purpose of this study was to evaluate the efficacy of conjunctival autograft with single intraoperative application of MMC 0.04% within 3 minutes in primary and recurrent pterygium and to compare this method with other’s. Sixty three patients (68 eyes: 50 eyes with primary and 18 eyes with recurrent pterygium) underwent pterygium excision with conjunctival autograft and single application of MMC 0.045/3 minutes. Patients were followed from 3 to 12 months after operation. Results: recurent rate of 1.96% (1 eye) was observed in the group of recurrent pterygium. There were 2 cases of superficial punctuate keratitis. Conclusion: this study indicates that intraoperative administration of a single dose of 0.04% MMC with conjunctival autograf is an effective treatment for prevention of recurrence of pterygium
Pterygium ; Transplantation, Autologous ; Mitomycin

No abstract available.
Humans ; Mitomycin* ; Trabeculectomy*

No abstract available.
Animals ; Caffeine* ; Mice* ; Mitomycin*

Objective: To determine the effect of topically administered bevacizumab on bleb survival and histology after trabeculectomy in rabbit eyes. Methods: This is an experimental interventional comparative animal study. Sixteen rabbit eyes underwent trabeculectomy, 8 of which were enhanced with intraoperative mitomycin-C. Eyes were randomized to receive either topical balanced salt solution (BSS) or topical bevacizumab at a concentration of 12.5 mg/mL. Intraocular pressure, bleb dimensions and vascularity grading were measured. IOP was recorded as a ratio of IOP of the experimental operated eye divided by the IOP of the contralateral control eye (IOPratio) as a function of time. Bleb morphology was recorded as a percentage of the maximum estimated bleb volume (% bleb) as a function of time. Bleb failure occurred if IOPratio ≥0.8, or if % bleb=0. The eyes were then submitted for histopathological analysis after bleb failure has occurred. Results: In plain trabeculectomy, the mean bleb survival in terms of IOP were 6.3 and 9.2 days in the BSS and topical bevacizumab groups respectively (ρ=0.25). In mitomycin-C-enhanced trabeculectomy, the mean bleb survival was 16 and 18.2 days respectively (ρ=0.40). In plain trabeculectomy, mean bleb survival in terms of bleb morphology were 8 and 12.2 days for the BSS and bevacizumab groups respectively (ρ=0.08). In enhanced trabeculectomy, mean bleb survival were 19.5 and 20 days respectively (ρ=0.99). Mean vascularity grading were 2 and 1.9 for the BSS groups, and 1.6 and 1.4 for the bevacizumab groups. Conclusion Topical bevacizumab as adjunctive therapy after trabeculectomy, whether plain or enhanced with mitomycin-C, showed a trend towards prolonged bleb survival, even though the results of this study were not statistically significant.
Bevacizumab ; Trabeculectomy ; Mitomycin

One of the major problems after pterygium removal are recurrence and complications of the adjunctive therapy. The author compared the recurrence rate, interval and age of the primary pterygium after surgical treatment and with(group 1:94 eyes) or without(group 2: 101 eyes) supple-mentary mitomycin-C therapy. All of whom had been treated by one surgeon using a pterygim and subconjunctival tissue removal and superior-inferor, sliding conjunctival flap to cover the pterygium defect, In group 1, supplementary mitomycin-C was topicall used. In group 1, three pterygia(3.2%) were recurred. Recurrence were more Likey after ealy polstperative wound disruption with flap retraction(2 of 3 recurrences), relativy uoung pationts(all recurrences are under 50), and recurrence occured at a mean interval of 3.8 months after surgery. In group 2, three pterygia(3.0%) were recurred. Recurrencd were monre likely after early postoperative wound disruption with flap retraction(all recurrences). young patients(all recurrences are under 45), and recurrence occured at a mean interval of 3.1 months after surgery. Between two group no significant difference in recurrence rate, age, and interval so pterygium surgical procedure, operator and early postoperative conjunctival flap state are more important factors than adjunctive therapy in recurrence.
Mitomycin ; Pterygium* ; Recurrence* ; Wounds and Injuries