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Eye (London, England) Jun 2020Pterygia are common conjunctival degenerations with well-documented risk factors but an unclear pathogenesis. Better understanding of the pathogenesis of pterygium could... (Review)
Review
Pterygia are common conjunctival degenerations with well-documented risk factors but an unclear pathogenesis. Better understanding of the pathogenesis of pterygium could lead to improved surgical outcomes and decreased postoperative recurrence. Currently, pterygium excision with conjunctival autograft remains the preferred surgical technique to decrease pterygium recurrence. Many adjuvant therapies have been used in pterygium surgery to varying degrees of success. Topical cyclosporine, an immunosuppressive medication, in conjunction with conjunctival autograft was found to be most successful in decreasing pterygium recurrence according to a recent meta-analysis. Other adjuvant therapies such as mitomycin-C (MMC), 5-fluorouracil (5-FU), and beta-irradiation have also been used, though usage of these may cause multiple adverse effects. Recent research indicates that interactions between mouse double minute 2 (MDM2) and p53 could play a role in the occurrence of pterygium. Nutlin, an MDM2 antagonist, was found to have significantly less toxicity in conjunctival cells when compared with MMC on laboratory analysis of pterygium samples.
Topics: Animals; Conjunctiva; Follow-Up Studies; Mice; Mitomycin; Ophthalmologic Surgical Procedures; Pterygium; Recurrence; Transplantation, Autologous
PubMed: 32029918
DOI: 10.1038/s41433-020-0786-3 -
Nature Aging May 2023The mysteries behind immune aging and its related inflammation are being unmasked. The research of Jin et al. reveals that the defective turnover of damaged mitochondria...
The mysteries behind immune aging and its related inflammation are being unmasked. The research of Jin et al. reveals that the defective turnover of damaged mitochondria in CD4 T cells from aged individuals results in the exacerbated secretion of mitochondrial DNA, fuelling inflammaging and impairing immune responses.
Topics: T-Lymphocytes; Mitomycin; Mitochondria
PubMed: 37198439
DOI: 10.1038/s43587-023-00412-2 -
Urologia Oct 2016If we think about the launch date of Mitomycin C, we could think that this supplement is very much focused on history of Medicine, and, yes, Mitomycin certainly has been...
If we think about the launch date of Mitomycin C, we could think that this supplement is very much focused on history of Medicine, and, yes, Mitomycin certainly has been a main contributor to the history of Urology. However, it is even more striking to think that even after fifty years of its use by Urologists worlwide, Mitomycin C remains an absolute "Must". The simplicity of use, the efficacy and the tolerability of Mitomycin explain its established role. In fact, "long standing" does not mean "old". The new technologies, introduced progressively in the last decades, have fully confirmed the present and future role of this drug, that is well illustrated in the articles contained in this supplement. I hope you will enjoy reading it and (re)discovering Mitomycin C.
Topics: Humans; Mitomycin
PubMed: 27768212
DOI: 10.5301/RU.2016.16271 -
Cell Communication and Signaling : CCS Jun 2023Cancer stem cells (CSCs) are considered to be responsible for tumor recurrence and metastasis. Therefore, clarification of the mechanisms involved in CSC stemness... (Review)
Review
Cancer stem cells (CSCs) are considered to be responsible for tumor recurrence and metastasis. Therefore, clarification of the mechanisms involved in CSC stemness maintenance and cell fate determination would provide a new strategy for cancer therapy. Unregulated cellular energetics has been accepted as one of the hallmarks of cancer cells, but recent studies have revealed that mitochondrial metabolism can also actively determine CSC fate by affecting nuclear stemness gene expression. Herein, from the perspective of mito-nuclear communication, we review recent progress on the influence of mitochondria on CSC potential from four aspects: metabolism, dynamics, mitochondrial homeostasis, and reactive oxygen species (ROS). Video Abstract.
Topics: Humans; Neoplasm Recurrence, Local; Cell Differentiation; Mitomycin; Mitochondria; Neoplastic Stem Cells; Reactive Oxygen Species
PubMed: 37370081
DOI: 10.1186/s12964-023-01160-x -
Journal Francais D'ophtalmologie Nov 2021Corneal haze represents subepithelial corneal fibrosis, a manifestation of a pathological healing process. It occurs as a result of an epithelial-stromal lesion... (Review)
Review
Corneal haze represents subepithelial corneal fibrosis, a manifestation of a pathological healing process. It occurs as a result of an epithelial-stromal lesion involving a break in the epithelial barrier. It is an inflammatory response that involves the migration, multiplication and differentiation of keratocytes into mature myofibroblasts, causing loss of corneal transparency. Although it is a transient phenomenon, this complication is feared following refractive photokeratectomy (PRK), because it can cause alterations in the quality of vision, refractive regression and decreased visual acuity. The severity of these symptoms is correlated with the severity of the corneal haze, which can be assessed clinically or by objective means such as corneal densitometry measurement. The frequency and severity of corneal haze increase with the depth of photoablation in PRK and are therefore increased during the treatment of severe ametropia. Considering that no consensus exists, the application of mitomycin C (MMC) intraoperatively and topical corticosteroids postoperatively are conventionally used to inhibit collagen synthesis, sometimes in combination with various protocols depending on the center or surgeon. This review of the literature reports the current knowledge on corneal haze, in order to better understand it and optimise its prevention in the context of a decreased MMC supply, which has occurred in the past and could recur in the future.
Topics: Cornea; Corneal Opacity; Humans; Lasers, Excimer; Mitomycin; Photorefractive Keratectomy
PubMed: 34538661
DOI: 10.1016/j.jfo.2021.05.006 -
Urology Jun 2015
Topics: Contracture; Humans; Intermittent Urethral Catheterization; Male; Mitomycin; Urethra; Urethral Stricture; Urinary Bladder Diseases
PubMed: 26099893
DOI: 10.1016/j.urology.2015.02.051 -
Turkish Journal of Ophthalmology Jun 2023Isolated from , mitomycin C (MMC) has various applications in the management of corneal and external disease due to its ability to modulate cellular proliferation. It... (Review)
Review
Isolated from , mitomycin C (MMC) has various applications in the management of corneal and external disease due to its ability to modulate cellular proliferation. It has been employed in pterygium surgery, ocular surface neoplasia, and refractive surgery. Currently, there is no definite consensus on the treatment protocols for each of the aforementioned applications. Although its benefits in the management of corneal and external diseases are promising, MMC use has potential complications including endothelial cell loss, corneal perforation, scleral melt, secondary glaucoma, iritis, and endophthalmitis. This article will review the literature regarding the use of MMC in the field of cornea and external disease and describe protocols employed with corresponding outcomes.
Topics: Humans; Mitomycin; Photorefractive Keratectomy; Lasers, Excimer; Cornea
PubMed: 37345314
DOI: 10.4274/tjo.galenos.2023.97932 -
Chemical Record (New York, N.Y.) Jan 2023Mitomycin C, (MC), an antitumor drug used in the clinics, is a DNA alkylating agent. Inert in its native form, MC is reduced to reactive mitosenes in cellulo which... (Review)
Review
Mitomycin C, (MC), an antitumor drug used in the clinics, is a DNA alkylating agent. Inert in its native form, MC is reduced to reactive mitosenes in cellulo which undergo nucleophilic attack by DNA bases to form monoadducts as well as interstrand crosslinks (ICLs). These properties constitute the molecular basis for the cytotoxic effects of the drug. The mechanism of DNA alkylation by mitomycins has been studied for the past 30 years and, until recently, the consensus was that drugs of the mitomycins family mainly target CpG sequences in DNA. However, that paradigm was recently challenged. Here, we relate the latest research on both MC and dicarbamoylmitomycin C (DMC), a synthetic derivative of MC which has been used to investigate the regioselectivity of mitomycins DNA alkylation as well as the relationship between mitomycins reductive activation pathways and DNA adducts stereochemical configuration. We also review the different synthetic routes to access mitomycins nucleoside adducts and oligonucleotides containing MC/DMC DNA adducts located at a single position. Finally, we briefly describe the DNA structural modifications induced by MC and DMC adducts and how site specifically modified oligonucleotides have been used to elucidate the role each adduct plays in the drugs cytotoxicity.
Topics: DNA Adducts; Mitomycin; DNA; Oligonucleotides
PubMed: 36251922
DOI: 10.1002/tcr.202200193 -
Bioorganic Chemistry Jun 2022While interstrand crosslinks (ICLs) have been considered as one type of DNA damage in the past, there is mounting evidence suggesting that these highly cytotoxic lesions...
While interstrand crosslinks (ICLs) have been considered as one type of DNA damage in the past, there is mounting evidence suggesting that these highly cytotoxic lesions are processed differently by the cellular machinery depending upon the ICL structure. In this study, we examined the crosslinking ability of three mitomycins, the structure of the ICLs they produce and the cytotoxicity of the drugs toward three different cell lines. The drugs are: mitomycin C (1), decarbamoylmitomycin C (2), and a mitomycin-conjugate (3) whose mitosane moiety is linked to a N-methylpyrrole carboxamide. We found that, overall, both MC and compound 3 show strong similarities regarding their alkylation of DNA, while DMC alkylating behavior is markedly different. To gain further insight into the mode of action of these drugs, we performed high throughput gene expression and gene ontology analysis to identify gene expression and cellular pathways most impacted by each drug treatment in MCF-7 cell lines. We observed that the novel mitomycin derivative (3) specifically causes changes in the expression of genes encoding proteins involved in cell integrity and tissue structure. Further analysis using bioinformatics (IPA) indicated that the new derivative (3) displays a stronger downregulation of major signaling networks that regulate the cell cycle, DNA damage response and cell proliferation when compared to MC and DMC. Collectively, these findings demonstrate that cytotoxic mechanisms of all three drugs are complex and are not solely related to their crosslinking abilities or the structure of the ICLs they produce.
Topics: Alkylation; DNA; DNA Adducts; DNA Damage; Humans; Mitomycin; Mitomycins
PubMed: 35349830
DOI: 10.1016/j.bioorg.2022.105744 -
Archivos Espanoles de Urologia May 2018Two Phase II studies, three Phase III and one observational study seem to justify that EMDA-MMC is a real alternative in the treatment of patients with NMIBC, especially... (Review)
Review
Two Phase II studies, three Phase III and one observational study seem to justify that EMDA-MMC is a real alternative in the treatment of patients with NMIBC, especially the high risk group. The phase III studies compare EMDA-MMC with passive diffusion MMC and BCG in patients with bladder TIS. They showed EMDA MMC superiority compared to passive diffusion MMC and similar to BCG in achieving complete response at 3 and 6 months. In another randomized study on pT1 NMIBC patients, comparing a sequential scheme of BCG plus EMDA-MMC and BCG, the sequential regimen was significantly superior than BCG reducing recurrence and progression and improved overall and specific survivals. A third randomized study compared TURBT only with immediate post TURBT MMC instillation and EMDA-MMC preoperative instillation. This latter showed to be superior in recurrence prevention than the other two schemes. Tolerance to EMDA-MMC is inferior to passive diffusion MMC, but it does not reach statistical significance. In the same way, EMDA-MMC tolerance is better than BCG and there is no difference between this and the sequential scheme of BCG plus EMDA-MMC. Methodological defects observed in these studies and the fact that almost all of them come from the same group makes it necessary to reproduce this data in other centers so that this therapeutic alternative could be included in guidelines.
Topics: Antibiotics, Antineoplastic; Electrochemotherapy; Humans; Mitomycin; Urinary Bladder Neoplasms
PubMed: 29745930
DOI: No ID Found