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Acta Ophthalmologica May 2023The purpose of the study was to investigate the incidence for endophthalmitis and blebitis after deep sclerectomy (DS) and trabeculectomy with routine use of Mitomycin C...
PURPOSE
The purpose of the study was to investigate the incidence for endophthalmitis and blebitis after deep sclerectomy (DS) and trabeculectomy with routine use of Mitomycin C (MMC) 0.4 mg/ml.
METHODS
Electronic medical records of patients who underwent surgery 1/2008-4/2020 were reviewed. Cumulative incidence for bleb-associated infection (BAI), including both endophthalmitis and blebitis, was calculated with cumulative incidence function (CIF) and Kaplan-Meier analysis. Risk factors for BAI were evaluated with univariate competing risk regression analysis and Log-rank analysis. Competing event in CIF was death.
RESULTS
In this retrospective single-centre cohort study, a total of 2653 patients and 3411 eyes underwent surgery: 3478 glaucoma surgeries, 2419 DS and 1059 trabeculectomies. Two cases of endophthalmitis and three of isolated blebitis developed. Median follow-up from the most recent surgery on the eye until the end of the study was 5.5 years, and until last visit at the ophthalmology department was 1.9 years. For the whole follow-up period in CIF-analysis, cumulative incidence for BAI was 0.16% (95% CI 0.06-0.36) at five years. Incidence was higher with eyes not treated with an antifibrotic during surgery (sub-hazard ratio 11.66, 95% CI 1.94-70.21, p = 0.007). Cumulative incidence between surgery and last visit with Kaplan-Meier analysis was 0.21% (95% CI 0.08-0.52) at five years, similarly, not using an antifibrotic increased incidence (Log-rank p < 0.001).
CONCLUSION
Cumulative incidence for BAI was low despite routine use of high-dose MMC.
Topics: Humans; Mitomycin; Trabeculectomy; Glaucoma; Retrospective Studies; Cohort Studies; Endophthalmitis
PubMed: 36352754
DOI: 10.1111/aos.15287 -
Current Opinion in Ophthalmology Mar 2021Mitomycin C (MMC) is an alkylating agent with extraordinary ability to crosslink DNA, preventing DNA synthesis. By this virtue, MMC is an important antitumor drug. In... (Review)
Review
PURPOSE OF REVIEW
Mitomycin C (MMC) is an alkylating agent with extraordinary ability to crosslink DNA, preventing DNA synthesis. By this virtue, MMC is an important antitumor drug. In addition, MMC has become the gold standard medication for glaucoma filtration surgery (GFS). This eye surgery creates a passage for drainage of aqueous humor (AqH) out of the eye into the sub-Tenon's space with the aim of lowering the intraocular pressure. A major cause of failure of this operation is fibrosis and scarring in the sub-Tenon's space, which will restrict AqH outflow. Intraoperative application of MMC during GFS has increased GFS success rate, presumably mainly by reducing fibrosis after GFS. However, still 10% of glaucoma surgeries fail within the first year.
RECENT FINDINGS
In this review, we evaluate risks and benefits of MMC as an adjuvant for GFS. In addition, we discuss possible improvements of its use by adjusting dose and method of administration.
SUMMARY
One way of improving GFS outcome is to prolong MMC delivery by using a drug delivery system.
Topics: Alkylating Agents; Drug Delivery Systems; Fibrosis; Filtering Surgery; Glaucoma; History, 20th Century; History, 21st Century; Humans; Intraocular Pressure; Mitomycin; Sclera
PubMed: 33315724
DOI: 10.1097/ICU.0000000000000729 -
Journal of the American Chemical Society Sep 2022Natural products containing an aziridine ring, such as mitomycin C and azinomycin B, exhibit antitumor activities by alkylating DNA via their aziridine rings; however,...
Natural products containing an aziridine ring, such as mitomycin C and azinomycin B, exhibit antitumor activities by alkylating DNA via their aziridine rings; however, the biosynthetic mechanisms underlying the formation of these rings have not yet been elucidated. We herein investigated the biosynthesis of vazabitide A, the structure of which is similar to that of azinomycin B, and demonstrated that Vzb10/11, with no similarities to known enzymes, catalyzed the formation of the aziridine ring via sulfate elimination. To elucidate the detailed reaction mechanism, crystallization of Vzb10/11 and the homologous enzyme, AziU3/U2, in the biosynthesis of azinomycin B was attempted, and the structure of AziU3/U2, which had a new protein fold overall, was successfully determined. The structural analysis revealed that these enzymes adjusted the dihedral angle between the amino group and the adjacent sulfate group of the substrate to almost 180° and enhanced the nucleophilicity of the C6-amino group temporarily, facilitating the S2-like reaction to form the aziridine ring. The present study reports for the first time the molecular basis for aziridine ring formation.
Topics: Aziridines; DNA; Mitomycin; Sulfates
PubMed: 35998388
DOI: 10.1021/jacs.2c07243 -
Aktuelle Urologie Apr 2018Bladder cancer is the second most common urological malignant disease. There are various treatment strategies which, depending on tumor stage and grade, can minimize... (Review)
Review
Bladder cancer is the second most common urological malignant disease. There are various treatment strategies which, depending on tumor stage and grade, can minimize recurrence and lower progression rate. Alternative treatment modalities of instillation therapy after failure with first line Mitomycin C or BCG do exist and have become a point of interest, especially in times of shortage of agents such as BCG.This article aims to give an overview of the current existing thermotherapeutic treatment options (electroinductive and electroconductive). The article starts with the first publication presenting thermochemotherapy with Mitomycin C using the Synergo device and highlights the first randomized controlled study comparing Mitomycin C (Synergo ) with conventional BCG therapy. The article also presents data about first conductive Mitomycin C therapy using the new Combat and the Unithermia device.Finally, it discusses in which cases thermotherapy with Mitomycin C can be applied safely based upon the current available data.
Topics: Antibiotics, Antineoplastic; BCG Vaccine; Disease Progression; Humans; Hyperthermia, Induced; Mitomycin; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 28926864
DOI: 10.1055/s-0043-109414 -
International Journal of Oncology Nov 2016Mitomycin C (MC), a commonly used anticancer drug, induces DNA damage via DNA alkylation. Decarbamoyl mitomycin C (DMC), another mitomycin lacking the carbamate at C10,...
Mitomycin C (MC), a commonly used anticancer drug, induces DNA damage via DNA alkylation. Decarbamoyl mitomycin C (DMC), another mitomycin lacking the carbamate at C10, generates similar lesions as MC. Interstrand cross-links (ICLs) are believed to be the lesions primarily responsible for the cytotoxicity of MC and DMC. The major ICL generated by MC (α-ICL) has a trans stereochemistry at the guanine-drug linkage whereas the major ICL from DMC (β-ICL) has the opposite, cis, stereochemistry. In addition, DMC can provoke strong p53-independent cell death. Our hypothesis is that the stereochemistry of the major unique β-ICL generated by DMC is responsible for this p53-independent cell death signaling. p53 gene is inactively mutated in more than half of human cancers. p21WAF1/CIP1 known as a major effector of p53 is involved in p53-dependent and -independent control of cell proliferation and death. This study revealed the role of p21WAF1/CIP1 on MC and DMC triggered cell damage. MCF-7 (p53-proficient) and K562 (p53-deficient) cells were used. Cell cycle distributions were shifted to the G1/S phase in MCF-7 treated with MC and DMC, but were shifted to the S phase in K562. p21WAF1/CIP1 activation was observed in both cells treated with MC and DMC, and DMC triggered more significant activation. Knocking down p53 in MCF-7 did not attenuate MC and DMC induced p21WAF1/CIP1 activation. The α-ICL itself was enough to cause p21WAF1/CIP1 activation.
Topics: Antibiotics, Antineoplastic; Apoptosis; Blotting, Western; Cell Cycle; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Gene Expression Regulation, Neoplastic; Humans; K562 Cells; MCF-7 Cells; Mitomycin; Tumor Suppressor Protein p53
PubMed: 27666201
DOI: 10.3892/ijo.2016.3703 -
Urologia Oct 2016Mitomycin C (MMC) as an intravesical chemotherapeutic agent is a well-known option for treatment of nonmuscle invasive bladder cancer (NMIBC) recurrence; it is probably... (Review)
Review
Mitomycin C (MMC) as an intravesical chemotherapeutic agent is a well-known option for treatment of nonmuscle invasive bladder cancer (NMIBC) recurrence; it is probably the most commonly used agent given its low rate of side effects and its efficacy.Both the American Urologic Association (AUA) and European Association of Urology (EAU) consider MMC as a standard treatment for immediate single-dose postoperative treatment and for adjuvant therapy in low and intermediate-risk NMIBC.Despite the popularity of this agent in the treatment of NMIBCs, many questions regarding the optimal approach to MMC therapy remain unanswered and the schedule widely used is empirical.Nevertheless, even when the current optimal approaches to MMC administration are used, a large proportion of NMIBCs recur.This apparent treatment resistance might be overcome by an optimization of standard MMC therapy or with a combination of MMC with other agents that have different mechanisms of action.Strategies to enhance passive delivery of MMC have been well studied and multiple measures are recommended for implementation of use in routine clinical practice.A modified scheme of instillation seems to be an easy and inexpensive alternative to increase efficacy of intravesical MMC and to also use this agent with an ablative intent.Enhancing tumor response with a sequential therapy is another option that has been investigated, mostly for chemo-immunotherapy wherein the different mechanisms of action of Bacillus of Calmette and Guerìn (BCG) and MMC are combined to achieve a higher response.
Topics: Antibiotics, Antineoplastic; Humans; Mitomycin; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 27647081
DOI: 10.5301/uro.5000193 -
The Journal of Urology Nov 2015
Topics: Female; Humans; Hyperthermia, Induced; Male; Mitomycin; Urinary Bladder Neoplasms
PubMed: 26239496
DOI: 10.1016/j.juro.2015.05.107 -
Bioorganic & Medicinal Chemistry Letters Dec 2022Mitomycin C (MMC) is a class of alkylating anticancer drug, which non-specifically interacts with nuclear DNA and cross-links guanine and cytosine of DNA, thereby...
Mitomycin C (MMC) is a class of alkylating anticancer drug, which non-specifically interacts with nuclear DNA and cross-links guanine and cytosine of DNA, thereby affecting DNA replication and synthesis. However, toxic effects largely impeded MMC's clinical applications. In this study, triphenylphosphine groups (TPP) were attached to MMC via the active aziridine amine with the aim to reduce its toxicity. MTT assay suggested that 5 possessed a good anticancer activity (IC = 1.09 μM, A549) with negligible effects on human normal cells (IC > 20 μM, L02 and HUVEC), while MMC exhibited IC values of less than 2.5 μM on the tested human normal cells. Dose range-finding experiments suggested that 5 had little effect on the body weight and tissues in mouse at a dose of 20 mg/kg, indicating significantly reduced toxicity as compared to MMC (LD < 2.5 mg/kg). Collectively, these data suggested that TPP group could be an effective vector to reduce toxicity of MMC.
Topics: Mice; Humans; Animals; Mitomycin; DNA
PubMed: 36280150
DOI: 10.1016/j.bmcl.2022.129036 -
Vestnik Oftalmologii 2022Despite the well-known effectiveness of pharmacological glaucoma therapy, surgical approach remains one of the main treatment options for some forms and stages of the... (Review)
Review
Despite the well-known effectiveness of pharmacological glaucoma therapy, surgical approach remains one of the main treatment options for some forms and stages of the disease. The long-term success of glaucoma surgery depends on the intensity of local wound healing processes at the surgical site. The most common way to influence healing processes in surgical treatment of glaucoma is the use of antimetabolites. However, given the high risk of serious complications associated with their use, the search for new drugs devoid of these disadvantages continues. The aim of this review is to describe the efficacy and safety of both currently used and upcoming pharmacological ways to influence the wound healing process after glaucoma surgery in order to improve the stability of hypotensive effect.
Topics: Filtering Surgery; Glaucoma; Humans; Mitomycin; Trabeculectomy; Wound Healing
PubMed: 36004602
DOI: 10.17116/oftalma2022138041136 -
Journal of Glaucoma Nov 2021The aim was to evaluate the effectiveness of bacterial cellulose membrane (BCM) in preventing fibrosis in trabeculectomy and the biocompatibility of BCM with conjunctiva...
PURPOSE
The aim was to evaluate the effectiveness of bacterial cellulose membrane (BCM) in preventing fibrosis in trabeculectomy and the biocompatibility of BCM with conjunctiva and sclera.
MATERIALS AND METHODS
Twenty-one eyes of 21 adult rabbits underwent fornix-based trabeculectomy. Standard surgery was done to control group (CG, n=7). Mitomycin-C (MMC) (0.3 mg/mL, 3 min) was applied to MMC group only (MMCG, n=7). BCM (~100 µm thick, 10×10 mm, single layer) was covered on the sclerotomy area before conjunctiva was closed in BCM group (BCMG, n=7). Intraocular pressures (IOP) were measured before, and 7, 14, 28, and 45 days after surgery (IOP-POD7, POD14, POD28, POD45). The IOP decrease were expressed as DIOP%-POD7, DIOP%-POD14, DIOP%-POD28, and DIOP%-POD45. The rabbits were sacrificed on the 45th day. Conjunctival vessel number, degrees of fibrosis, total inflammation, foreign body reaction, inflammatory cell types (B cells, T cells, plasma cells), macrophages, bleb spaces and the expression of α-smooth muscle actin were studied using histopathology and immunohistochemistry techniques. The groups were compared using nonparametric tests.
RESULTS
There was no statistically significant difference between the groups regarding baseline IOP and DIOP%-POD7 (P>0.05). While DIOP%-POD14, 28 and 45 were similar between BCMG and MMCG, they were significantly lower in CG (P<0.05). The lowest conjunctival vessel number was detected in the MMCG but the difference was not significant. There was no difference between BCMG and CG with regard to the numbers of B cells, T cells, and macrophages, however, these cells were significantly lower in MMCG (P<0.05). Five cases had mild and 2 cases had moderate foreign body reaction in the BCMG. There was mild to moderate inflammation in all BCM cases. While fibrosis and α-smooth muscle actin staining were higher in the CG (P<0.001), they were minimal in the BCM and MMCGs.
CONCLUSIONS
BCM showed good biocompatibility and provided better control of IOP with minimal fibrosis at the trabeculectomy site compared with the control group.
Topics: Animals; Cellulose; Conjunctiva; Fibrosis; Intraocular Pressure; Mitomycin; Rabbits; Sclera; Trabeculectomy
PubMed: 34224487
DOI: 10.1097/IJG.0000000000001907