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The Cochrane Database of Systematic... 2001Trabeculectomy is performed as a treatment for many types of glaucoma in an attempt to lower the intra-ocular pressure. Mitomycin C is an antimetabolite applied between... (Review)
Review
BACKGROUND
Trabeculectomy is performed as a treatment for many types of glaucoma in an attempt to lower the intra-ocular pressure. Mitomycin C is an antimetabolite applied between the sclera and conjunctiva during the initial stages of a trabeculectomy to prevent excessive post-operative scarring and thus reduce the risk of failure.
OBJECTIVES
The objective of this review is to assess the effects of intra-operative application of mitomycin C in eyes of people undergoing trabeculectomy.
SEARCH STRATEGY
We searched the Cochrane Eyes and Vision Group specialised register, The Cochrane Controlled Trials Register - CENTRAL, MEDLINE, EMBASE and the reference lists of relevant articles. We used the Science Citation Index to search for articles that cited the included studies. We contacted investigators and experts for details of additional relevant trials.
SELECTION CRITERIA
We included randomised trials of intra-operative mitomycin C compared to placebo in trabeculectomy.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial quality and extracted data. We contacted trial investigators for missing information. Data were summarised using relative risk, odds ratio and weighted mean difference.
MAIN RESULTS
This review includes 11 trials involving a total of 698 participants. The trials included three types of participants (those at high risk of failure, those undergoing trabeculectomy combined with cataract surgery, and those with no previous surgical intervention). Mitomycin C appears to be effective in reducing the relative risk of failure of trabeculectomy both in eyes at high risk of failure (relative risk 0.32, 95% confidence interval 0.20 to 0.53) and those undergoing surgery for the first time (relative risk 0.29, 95% confidence interval 0.16 to 0.53). No significant effect on failure was noted in the group undergoing trabeculectomy combined with cataract extraction. Mean intra-ocular pressure was significantly reduced at 12 months in all three participant groups receiving mitomycin C compared to placebo. No significant increase in permanent sight threatening complications was detected. Some evidence exists that mitomycin C increases the risk of cataract. The quality of trial reporting is poor in eight trials. Repeat analysis with three trials rated as low risk of bias did not yield different results.
REVIEWER'S CONCLUSIONS
Intra-operative mitomycin C reduces the risk of surgical failure in eyes that have undergone no previous surgery and in eyes at high risk of failure. Compared to placebo it reduces mean intra-ocular pressure at 12 months in all groups of participants in this review. Apart from an increase in cataract formation following mitomycin C, no demonstrable significant increase in other side effects was detected.
Topics: Antimetabolites; Cataract Extraction; Cicatrix; Glaucoma; Humans; Intraoperative Period; Mitomycin; Randomized Controlled Trials as Topic; Trabeculectomy; Treatment Failure
PubMed: 11279773
DOI: 10.1002/14651858.CD002897 -
Proceedings of the Society For... Nov 1956
Topics: Antihypertensive Agents; Antimetabolites; Humans; Serotonin; Serotonin Antagonists
PubMed: 13379467
DOI: 10.3181/00379727-93-22712 -
The Journal of Antibiotics Aug 1985The molecular formula of a new antimetabolite produced by Streptomyces purpurascens was determined to be C5H5N5O2 by elemental analysis, FD-MS and 13C NMR. Reduction of...
The molecular formula of a new antimetabolite produced by Streptomyces purpurascens was determined to be C5H5N5O2 by elemental analysis, FD-MS and 13C NMR. Reduction of this antimetabolite with Raney nickel yielded guanine. The antimetabolite was distinguishable from known N-hydroxyguanines by comparison of their UV spectra. The structure of the antimetabolite was finally established to be 7-hydroxyguanine by X-ray crystallography.
Topics: Antimetabolites, Antineoplastic; Chemical Phenomena; Chemistry; Guanine; X-Ray Diffraction
PubMed: 3840158
DOI: 10.7164/antibiotics.38.977 -
JAMA Jan 1966
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Science (New York, N.Y.) Dec 1966
Topics: Anti-Bacterial Agents; Antimetabolites; Biotin; Streptomyces
PubMed: 5924200
DOI: 10.1126/science.154.3757.1667 -
The American Journal of Clinical... 1955
Topics: Antimetabolites; Humans; Methionine; Pseudomonas
PubMed: 14398647
DOI: 10.1093/ajcn/3.4.305 -
General Pharmacology Nov 19981. Primary and secondary resistance to the widely used antimetabolite 5-fluorouracil (5-FU) are common phenomena in cancer chemotherapy. Because 5-FU still remains the... (Review)
Review
1. Primary and secondary resistance to the widely used antimetabolite 5-fluorouracil (5-FU) are common phenomena in cancer chemotherapy. Because 5-FU still remains the agent of choice in the treatment of, for example, colorectal cancer, circumvention of resistance is of vital importance. 2. Resistance to fluoropyrimidines is a multifactorial event, which includes transport mechanisms, metabolism, molecular mechanisms, protection from apoptosis, and resistance via cell cycle kinetics. To date, the prediction of primary resistance to 5-FU in the clinic is limited to few studies focusing mainly on the key enzyme thymidylate synthase. To gain a deeper insight into the key events responsible for 5-FU resistance in vivo, the evaluation of additional parameters such as other (fluoro)pyrimidine converting enzymes, the mutational status of regulators of apoptosis, and tumour angiogenesis is currently under investigation. 3. Most studies on the circumvention of fluoropyrimidine resistance refer to preclinical investigations and were rarely confirmed in clinical trials. Although our understanding of resistance to 5-FU leaves many open questions, the fundamental insights accomplished during the last years provide a rational understanding to exceed the bounds of the actual therapeutic schedules.
Topics: Animals; Antimetabolites, Antineoplastic; Apoptosis; Biological Transport; Cell Cycle; Drug Resistance, Neoplasm; Fluorouracil; Humans
PubMed: 9809460
DOI: 10.1016/s0306-3623(98)00191-8 -
Journal of Glaucoma Sep 2008To assess the pattern of use of antimetabolites and steroids in trabeculectomy surgery among consultant ophthalmologists in Australia and New Zealand.
AIM
To assess the pattern of use of antimetabolites and steroids in trabeculectomy surgery among consultant ophthalmologists in Australia and New Zealand.
METHOD
A postal questionnaire of 25 questions regarding current glaucoma practices and antimetabolite and steroid use in trabeculectomy surgery was sent to all practicing Australian and New Zealand Fellows of the Royal Australia and New Zealand College of Ophthalmologists in July 2005. The second half of the survey consisted of questions on the number of trabeculectomies performed per year, topical steroid use, the type of antimetabolite used, and assessment of factors that may influence the decision to use them. The results were cross-tabulated according to state/country, years practicing, type of practice, and being a glaucoma subspecialist (GSS).
RESULTS
The overall response rate was 78% (627 out of 808). Ninety-one percent stated that they managed glaucoma of which 65% stated that they perform trabeculectomy surgery and 16% considered themselves as a GSS. In 2004, 75% of ophthalmologists performed less than 10 trabeculectomies. Sixty-one percent used an antimetabolite in trabeculectomy surgery of which 5-fluorouracil was used 51% (intraoperatively) and 24% (postoperatively). Mitomycin C was used in 12% and 0.2 mg/mL was the most commonly used concentration for 2 or 3 minutes. Fifty-four percent used postoperative steroids in a primary trabeculectomy for 1 to 2 months with 48% of GSSs using it for 2 to 3 months. Forty-eight percent to 96% would use an antimetabolite in patients with risk factors for conjunctival scarring.
CONCLUSIONS
This survey shows a wide range of the use of antimetabolites and steroids in trabeculectomy surgery with 5-fluorouracil being most commonly used. GSSs and young ophthalmologists would use antimetabolites more often and postoperative steroids for longer. This survey allows ophthalmologists to compare their own practices with those of their colleagues in Australia and the United Kingdom.
Topics: Antimetabolites; Australia; Cross-Sectional Studies; Fluorouracil; Glaucoma; Glucocorticoids; Health Care Surveys; Humans; Mitomycin; New Zealand; Ophthalmology; Practice Patterns, Physicians'; Surveys and Questionnaires; Trabeculectomy
PubMed: 18794674
DOI: 10.1097/IJG.0b013e31816224d8 -
Cellular and Molecular Life Sciences :... Mar 2009The anti-metabolite 5-fluorouracil (5-FU) is employed clinically to manage solid tumors including colorectal and breast cancer. Intracellular metabolites of 5-FU can... (Review)
Review
The anti-metabolite 5-fluorouracil (5-FU) is employed clinically to manage solid tumors including colorectal and breast cancer. Intracellular metabolites of 5-FU can exert cytotoxic effects via inhibition of thymidylate synthetase, or through incorporation into RNA and DNA, events that ultimately activate apoptosis. In this review, we cover the current data implicating DNA repair processes in cellular responsiveness to 5-FU treatment. Evidence points to roles for base excision repair (BER) and mismatch repair (MMR). However, mechanistic details remain unexplained, and other pathways have not been exhaustively interrogated. Homologous recombination is of particular interest, because it resolves unrepaired DNA intermediates not properly dealt with by BER or MMR. Furthermore, crosstalk among DNA repair pathways and S-phase checkpoint signaling has not been examined. Ongoing efforts aim to design approaches and reagents that (i) approximate repair capacity and (ii) mediate strategic regulation of DNA repair in order to improve the efficacy of current anticancer treatments.
Topics: Animals; Antimetabolites, Antineoplastic; Cell Cycle; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA Repair Enzymes; Fluorouracil; Humans; Molecular Structure; Signal Transduction
PubMed: 18979208
DOI: 10.1007/s00018-008-8557-5 -
Expert Review of Anticancer Therapy Apr 2008Gemcitabine (2 ,2 -difluorodeoxycytidine) is a deoxycytidine-analog antimetabolite with broad activity against a variety of solid tumors and lymphoid malignancies. It... (Review)
Review
Gemcitabine (2 ,2 -difluorodeoxycytidine) is a deoxycytidine-analog antimetabolite with broad activity against a variety of solid tumors and lymphoid malignancies. It was approved as standard of care in patients with pancreatic cancer one decade ago, based primarily on improvement in clinical benefit response such as pain reduction, improvement in Karnofsky performance status and increase in body weight. This article gives an overview of the pharmacodynamics and pharmacokinetics of gemcitabine, highlights the clinical activity of gemcitabine and summarizes the treatment options in metastatic pancreatic cancer with focus on gemcitabine-based chemotherapy. The emerging role of combinations of gemcitabine with novel targeted agents, including small-molecule inhibitors and other investigational drugs, is also discussed.
Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Humans; Infusions, Intravenous; Neoplasm Metastasis; Pancreatic Neoplasms; Gemcitabine
PubMed: 18402518
DOI: 10.1586/14737140.8.4.511