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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 -
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 -
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 -
Frontiers in Medicine 2022Superficial keratectomy (SK) is the manual dissection of the superficial corneal layers (epithelium, Bowman's layer, and sometimes superficial stroma). SK is done using... (Review)
Review
Superficial keratectomy (SK) is the manual dissection of the superficial corneal layers (epithelium, Bowman's layer, and sometimes superficial stroma). SK is done using a surgical blade or diamond burr. Some surgeons use intraoperative mitomycin C 0.02% or amniotic membrane transplantation to improve surgical outcomes. This literature review shows that SK remains an effective method for different indications, including tissue diagnosis, excision of corneal degenerations, dystrophies, scarring, recurrent corneal erosions, and retained corneal foreign body.
PubMed: 35872789
DOI: 10.3389/fmed.2022.915284 -
Investigative and Clinical Urology Jul 2021Urothelial carcinoma of the upper urinary tract is uncommon and presents unique challenges for diagnosis and management. Nephroureterectomy has been the preferred... (Review)
Review
Urothelial carcinoma of the upper urinary tract is uncommon and presents unique challenges for diagnosis and management. Nephroureterectomy has been the preferred management option, but it is associated with significant morbidity. Nephron-sparing treatments are a valuable alternative and provide similar efficacy in select cases. A PubMed literature review was performed in English language publications using the following search terms: urothelial carcinoma, upper tract, nephron-sparing, intraluminal and systemic therapy. Contemporary papers published within the last 10 years were primarily included. Where encountered, systematic reviews and meta-analyses were given priority, as were randomized controlled trials for newer treatments. Core guidelines were referenced and citations reviewed for inclusion. A summary of epidemiological data, clinical diagnosis, staging, and treatments focusing on nephron-sparing approaches to upper tract urothelial carcinoma (UTUC) are outlined. Nephron-sparing management strategies are viable options to consider in patients with favorable features of UTUC. Adjunctive therapies are being investigated but the data remains mixed. Protocol variability and dosage differences limit statistical interpretation. New mechanisms to improve treatment dwell times in the upper tracts are being designed with promising preliminary results. Studies investigating systemic therapies are ongoing but implications for nephron-sparing management are uncertain. Nephron-sparing management is an acceptable treatment modality best suited for favorable disease. More work is needed to determine if intraluminal and/or systemic therapies can further optimize treatment outcomes beyond resection alone.
Topics: Adjuvants, Immunologic; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Carcinoma, Transitional Cell; Deoxycytidine; Humans; Kidney Neoplasms; Mitomycin; Neoplasm Staging; Nephrectomy; Nephrons; Organ Sparing Treatments; Ureteral Neoplasms; Ureteroscopy; Gemcitabine
PubMed: 34190434
DOI: 10.4111/icu.20210113 -
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 -
Ophthalmic Plastic and Reconstructive...This study aimed to report the performance of the large language model ChatGPT (OpenAI, San Francisco, CA, U.S.A.) in the context of lacrimal drainage disorders.
PURPOSE
This study aimed to report the performance of the large language model ChatGPT (OpenAI, San Francisco, CA, U.S.A.) in the context of lacrimal drainage disorders.
METHODS
A set of prompts was constructed through questions and statements spanning common and uncommon aspects of lacrimal drainage disorders. Care was taken to avoid constructing prompts that had significant or new knowledge beyond the year 2020. Each of the prompts was presented thrice to ChatGPT. The questions covered common disorders such as primary acquired nasolacrimal duct obstruction and congenital nasolacrimal duct obstruction and their cause and management. The prompts also tested ChatGPT on certain specifics, such as the history of dacryocystorhinostomy (DCR) surgery, lacrimal pump anatomy, and human canalicular surfactants. ChatGPT was also quizzed on controversial topics such as silicone intubation and the use of mitomycin C in DCR surgery. The responses of ChatGPT were carefully analyzed for evidence-based content, specificity of the response, presence of generic text, disclaimers, factual inaccuracies, and its abilities to admit mistakes and challenge incorrect premises. Three lacrimal surgeons graded the responses into three categories: correct, partially correct, and factually incorrect.
RESULTS
A total of 21 prompts were presented to the ChatGPT. The responses were detailed and were based according to the prompt structure. In response to most questions, ChatGPT provided a generic disclaimer that it could not give medical advice or professional opinion but then provided an answer to the question in detail. Specific prompts such as "how can I perform an external DCR?" were responded by a sequential listing of all the surgical steps. However, several factual inaccuracies were noted across many ChatGPT replies. Several responses on controversial topics such as silicone intubation and mitomycin C were generic and not precisely evidence-based. ChatGPT's response to specific questions such as canalicular surfactants and idiopathic canalicular inflammatory disease was poor. The presentation of variable prompts on a single topic led to responses with either repetition or recycling of the phrases. Citations were uniformly missing across all responses. Agreement among the three observers was high (95%) in grading the responses. The responses of ChatGPT were graded as correct for only 40% of the prompts, partially correct in 35%, and outright factually incorrect in 25%. Hence, some degree of factual inaccuracy was present in 60% of the responses, if we consider the partially correct responses. The exciting aspect was that ChatGPT was able to admit mistakes and correct them when presented with counterarguments. It was also capable of challenging incorrect prompts and premises.
CONCLUSION
The performance of ChatGPT in the context of lacrimal drainage disorders, at best, can be termed average. However, the potential of this AI chatbot to influence medicine is enormous. There is a need for it to be specifically trained and retrained for individual medical subspecialties.
Topics: Humans; Dacryocystorhinostomy; Lacrimal Duct Obstruction; Nasolacrimal Duct; Mitomycin; Intubation; Silicones
PubMed: 37166289
DOI: 10.1097/IOP.0000000000002418 -
European Urology Focus May 2023The ablative effect of intravesical therapy is known for decades. However, the clinical feasibility and efficacy of chemoablation for non-muscle-invasive bladder cancer... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
The ablative effect of intravesical therapy is known for decades. However, the clinical feasibility and efficacy of chemoablation for non-muscle-invasive bladder cancer (NMIBC) have not become accepted.
OBJECTIVE
To assess the treatment outcomes of chemoablation for NMIBC and to compare its safety with that of the standard treatment, transurethral resection of bladder tumors (TURBT) followed by intravesical therapy.
EVIDENCE ACQUISITION
Multiple databases were queried in July 2022 for studies investigating the complete response (CR) rates and adverse events in NMIBC patients treated with chemoablation using mitomycin C (MMC), gemcitabine, epirubicin, or bacillus Calmette-Guérin.
EVIDENCE SYNTHESIS
Overall, 23 studies comprising 1199 patients were eligible for this meta-analysis. Among these studies, 20 assessed the efficacy of chemoablation and three compared the treatment outcomes of MMC chemoablation versus standard treatment. Among patients treated with weekly administration of any agent, the pooled CR rates at initial assessment were 50.9% (95% confidence interval [CI]: 45.9-55.9) for the marker lesion and 47.5% (95% CI: 36.5-58.7) for well-selected NMIBC (ie, small tumors and/or a small number of tumors). Novel regimens for chemoablation such as MMC-gel (70.6%, 95% CI: 60.1-79.3) and an intensive MMC regimen (64.7%, 95% CI: 56.2-72.3) provided better CR rates in well-selected NMIBC patients. Comparable CR rates were noted irrespective of tumor multiplicity, whereas tumor size <5 mm was associated with a higher CR rate than tumor size ≥5 mm (odds ratio: 0.36, 95% CI: 0.17-0.79). The novel intensive MMC regimen resulted in lower rates of dysuria and urinary frequency than standard treatment.
CONCLUSIONS
Despite the lack of long-term outcomes, chemoablation appears to be a promising treatment option for well-selected NMIBC patients and can potentially help avoid unnecessary TURBT, specifically in some elderly patients with intermediate-risk NMIBC. Further well-designed studies with larger cohorts are necessary to address the differential tolerability and long-term anticancer efficacy of this resurging approach.
PATIENT SUMMARY
Bladder instillation therapy has a potential ablative effect for well-selected non-muscle-invasive bladder cancer. This can lead to the omission of an unnecessary surgical treatment.
Topics: Humans; Aged; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Mitomycin; Gemcitabine; Administration, Intravesical
PubMed: 36517409
DOI: 10.1016/j.euf.2022.12.003 -
The Urologic Clinics of North America Feb 2020Non-muscle-invasive bladder cancer can be a challenging disease to manage. In recent years, hyperthermia therapy in conjunction with intravesical therapy has been... (Review)
Review
Non-muscle-invasive bladder cancer can be a challenging disease to manage. In recent years, hyperthermia therapy in conjunction with intravesical therapy has been gaining traction as a treatment option for bladder cancer, especially if Bacillus Calmette-Guerin might not be available. Trials of intravesical chemotherapy with heat are few and there has been considerable heterogeneity between studies. However, multiple new trials have accrued and high-quality data are forthcoming. In this review, we discuss the role of combined intravesical hyperthermia and chemotherapy as a novel approach for the treatment of bladder cancer.
Topics: Administration, Intravesical; Antibiotics, Antineoplastic; Humans; Hyperthermia, Induced; Mitomycin; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 31757301
DOI: 10.1016/j.ucl.2019.09.008 -
Molecules (Basel, Switzerland) May 2021This review article provides a perspective on the synthesis of alicyclic and heterocyclic ring-fused benzimidazoles, imidazo[4,5-]benzimidazoles, and... (Review)
Review
This review article provides a perspective on the synthesis of alicyclic and heterocyclic ring-fused benzimidazoles, imidazo[4,5-]benzimidazoles, and imidazo[5,4-]benzimidazoles. These heterocycles have a plethora of biological activities with the iminoquinone and quinone derivatives displaying potent bioreductive antitumor activity. Synthesis is categorized according to the cyclization reaction and mechanisms are detailed. Nitrobenzene reduction, cyclization of aryl amidines, lactams and isothiocyanates are described. Protocols include condensation, cross-dehydrogenative coupling with transition metal catalysis, annulation onto benzimidazole, often using CuI-catalysis, and radical cyclization with homolytic aromatic substitution. Many oxidative transformations are under metal-free conditions, including using thermal, photochemical, and electrochemical methods. Syntheses of diazole analogues of mitomycin C derivatives are described. Traditional oxidations of -(cycloamino)anilines using peroxides in acid via the -amino effect remain popular.
Topics: Benzimidazoles; Cyclization; Imidazoles; Mitomycin
PubMed: 34064312
DOI: 10.3390/molecules26092684