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The Laryngoscope Jan 2013To describe the presentation, stenosis characteristics, etiological differences, and outcomes of adult laryngotracheal stenosis treated with endoscopic cold incision,...
OBJECTIVES/HYPOTHESIS
To describe the presentation, stenosis characteristics, etiological differences, and outcomes of adult laryngotracheal stenosis treated with endoscopic cold incision, balloon dilation, topical mitomycin C application, and steroid injection.
STUDY DESIGN
Retrospective chart review.
METHODS
Demographic and clinical data were extracted for patients treated between March 2000 and December 2010. Prolonged intubation and idiopathic patient data were utilized for comparative analysis.
RESULTS
Eighty patients (65 females; 15 males; 220 procedures; 2.9 years mean follow-up) presented with dyspnea (81%) and/or exercise intolerance (40%). Most commonly, etiologies were idiopathic (53 of 80; 66%) or prolonged intubation (14 of 80; 18%). Mean procedures per patient and interval between procedures were 2.8 procedures and 405 days, respectively. Mean stenosis length and distance from the caudal phonating edge of the true vocal folds were 9 mm and 19 mm. Complication, tracheotomy, and open-procedure rates were 1.8%, 1.4%, and 10.0%, respectively. Patients with more than two procedures demonstrated a mean 4-mm reduction in stenosis length and a 2-mm cephalad progression of stenosis over time. More caudal stenoses required more frequent procedures. Procedures were less frequent as more procedures were performed. Stenosis characteristics, interval between procedures, and total procedures were similar between idiopathic patients with or without intubation histories, but different between idiopathic and prolonged intubation patients.
CONCLUSIONS
This procedure was shown to be a viable option in adult laryngotracheal stenosis. Repeat dilation was likely, but was performed without adversely affecting stenosis characteristics. Stenoses farther from the vocal folds required procedures more frequently. Idiopathic patients with a history of brief, elective intubation had stenosis characteristics and responses to therapy similar to idiopathic patients without an intubation history. Both idiopathic groups together demonstrated stenosis characteristics and responses to therapy dissimilar to patients with a history of prolonged intubation.
Topics: Adult; Endoscopy; Female; Follow-Up Studies; Humans; Laryngostenosis; Male; Mitomycin; Retrospective Studies; Steroids; Tracheal Stenosis; Treatment Outcome
PubMed: 23086662
DOI: 10.1002/lary.23638 -
Biochemistry Jun 2019Mitomycins make up a group of antitumor natural products that are biosynthesized from aminohydroxybenzoic acid (AHBA) and N-acetylglucosamine (GlcNAc). While the...
Mitomycins make up a group of antitumor natural products that are biosynthesized from aminohydroxybenzoic acid (AHBA) and N-acetylglucosamine (GlcNAc). While the biosynthetic gene cluster was reported two decades ago, the mechanism by which the two building blocks, AHBA and GlcNAc, are coupled during biosynthesis remained uncharacterized. Here we report evidence that AHBA is first loaded onto an MmcB acyl carrier protein (ACP) by a MitE acyl ACP synthetase, followed by a transfer of GlcNAc from UDP-GlcNAc by MitB. The results suggest that the early steps of mitomycin biosynthesis proceed via intermediates linked to MmcB.
Topics: Acyl Carrier Protein; Aminobenzoates; Carbon-Sulfur Ligases; Enzyme Assays; Hydroxybenzoates; Kinetics; Mitomycin; N-Acetylglucosaminyltransferases; Streptomyces
PubMed: 31188570
DOI: 10.1021/acs.biochem.9b00379 -
International Journal of Hyperthermia :... Aug 2018Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in patients with peritoneal disease but is...
INTRODUCTION
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in patients with peritoneal disease but is associated with significant morbidity. We evaluate the perioperative complications and the association with the chemotherapy agent used for HIPEC.
METHODS
Retrospective analysis of a prospectively collected database of CRS-HIPEC cases between April 2001 and February 2016 was performed. Patients were stratified by the chemotherapy used, and perioperative complications were compared.
RESULTS
Out of 214 CRS-HIPEC cases, 113 procedures used Mitomycin-C(MMC), 92 used cisplatin, 8 used oxaliplatin and the HIPEC regimen for one procedure was not recorded and excluded. 94 patients (44%) suffered low-grade complications (grade I-II), and 49 patients (23%) suffered high-grade complications (grade III-V). The frequency of low-grade complications for the cisplain, oxaliplatin and MMC groups were 49%, 50% and 40%, respectively, whereas that of high-grade complications were 24%, 50% and 20%, respectively. HIPEC with platinum agents was associated with a higher rate of acute renal impairment (ARI) compared to MMC (32% and 62% for cisplatin and oxaliplatin vs. 5.6% for MMC), whereas grade IV ARI requiring dialysis occurred only in the cisplatin group (5.6%). HIPEC with oxaliplatin was associated with higher rates of post-operative bleeding (25% vs. 1.1% and 0.88%). Rates of other complications did not differ significantly between the groups receiving different HIPEC regimens.
CONCLUSIONS
The overall complication rates do not significantly differ after HIPEC with MMC and platinum based agents. Renal impairment tends to be more common and of greater severity when a platinum agent is used, whereas oxaliplatin is associated with significant post-operative bleeding.
Topics: Cytoreduction Surgical Procedures; Female; Humans; Hyperthermia, Induced; Male; Middle Aged; Mitomycin; Organoplatinum Compounds; Prospective Studies; Retrospective Studies; Survival Analysis
PubMed: 28633580
DOI: 10.1080/02656736.2017.1345014 -
PloS One 2022This unicentric randomized clinical trial was designed to compare the surgical outcomes of mitomycin C-enhanced trabeculectomy (MMC-TRAB) with and without subtenon... (Randomized Controlled Trial)
Randomized Controlled Trial
This unicentric randomized clinical trial was designed to compare the surgical outcomes of mitomycin C-enhanced trabeculectomy (MMC-TRAB) with and without subtenon triamcinolone acetonide (TAAC) injection in patients with non-inflammatory glaucomas. This trial is registered at the Brazilian Registry of Clinical Trials (ReBEC) under the register number RBR-53f8nh. Consecutive non-inflammatory glaucoma patients requiring surgical intervention were randomized into two groups. In the control group, eyes underwent standard MMC-TRAB, while in the intervention group, besides the standard MMC-TRAB, these eyes also received a subtenon TAAC injection (4mg) close to the bleb site at the end of the surgery. The main outcomes of the study were surgical success rates, intraocular pressure (IOP) and number of medications at all timepoints. Success was defined as IOP ≤ 15 mmHg and subdivided in complete or qualified according to the need of medication. A total of 75 eyes of 63 different patients were included (intervention group = 39 eyes; control group = 36 eyes). There was no difference between groups at baseline (p>0.11). Multivariable regression analysis indicated that IOP levels were significantly lower in the intervention group at 18 and 24 months of follow-up when number of medications was considered as a covariate (P<0.001). Complete success rates were higher in the intervention group at 06 (90.9% vs 68.7%; p = 0.03), 12 (87.2% vs 66.7%; p = 0.02) and 18 months (87.2% vs 66.7%; p = 0.02). Additionally, although success rates at 24 months were higher in the intervention group (82.0% vs 66.7%; p = 0.09), this difference did not reach statistical significance. Qualified success rates did not significantly differ between groups at all timepoints. In conclusion, this study found significantly lower IOPs levels at 18 and 24 months of follow-up and higher complete success rates until 18 months of follow-up, with the use of subtenon TAAC as an adjuvant to standard MMC-TRABs in non-inflammatory glaucoma patients.
Topics: Follow-Up Studies; Glaucoma; Humans; Intraocular Pressure; Mitomycin; Trabeculectomy; Treatment Outcome; Triamcinolone
PubMed: 35617211
DOI: 10.1371/journal.pone.0268623 -
Acta Ophthalmologica Feb 2023The aim of this study was to evaluate docosahexaenoic acid (DHA) as a potential antifibrotic agent after glaucoma filtration surgery (GFS) in rats.
PURPOSE
The aim of this study was to evaluate docosahexaenoic acid (DHA) as a potential antifibrotic agent after glaucoma filtration surgery (GFS) in rats.
METHODS
A total of 36 10-week-old Brown Norway rats underwent GFS. Animals were equally divided into three groups: a control group, a DHA group and a mitomycin C (MMC) group. Intraocular pressure (IOP) was measured using a dynamic rebound tonometer, and a photograph of the surgical site was taken on days 1, 3, 7, 10, 14 and 17. The incorporation of DHA into fibroblasts was evaluated by gas chromatography. The expression of alfa-smooth muscle actin (α-SMA) and Smad proteins was assessed by Western blotting.
RESULTS
IOP decreased after surgery in animals from the three groups on day 1 after surgery. Over time, IOP remained lower in the DHA and MMC groups than in the control group (median [interquartile range] 8.0 [7.0-8.0] and 8.0 [7.3-8.0] mmHg vs. 9.0 [8.0-9.0] mmHg, respectively; p < 0.001). Bleb area in the DHA and MMC groups remained larger than that of the control group from day 7 to day 14 (3.9 [2.9-5.2] and 3.5 [2.3-4.4] mm vs. 2.3 [2.0-2.8] mm , respectively; p = 0.0021). We did not observe any change in DHA concentrations in the fibroblasts of the DHA group compared with the other groups.
CONCLUSION
The impact of DHA on IOP and bleb area was similar to that of MMC. The mechanisms of action of DHA in rat eye fibroblasts deserve further investigation.
Topics: Animals; Rats; Disease Models, Animal; Docosahexaenoic Acids; Fibrosis; Filtering Surgery; Glaucoma; Intraocular Pressure; Mitomycin; Trabeculectomy
PubMed: 35920328
DOI: 10.1111/aos.15222 -
The Journal of Urology Jan 2022Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor...
Primary Chemoablation of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer Using UGN-102, a Mitomycin-Containing Reverse Thermal Gel (Optima II): A Phase 2b, Open-Label, Single-Arm Trial.
PURPOSE
Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC.
MATERIALS AND METHODS
This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial.
RESULTS
A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue.
CONCLUSIONS
Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.
Topics: Ablation Techniques; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Female; Humans; Hydrogels; Male; Middle Aged; Mitomycin; Neoplasm Grading; Neoplasm Invasiveness; Prospective Studies; Risk Assessment; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 34433303
DOI: 10.1097/JU.0000000000002186 -
International Journal of Molecular... Jan 2024The link between mitochondria and major depressive disorder (MDD) is increasingly evident, underscored both by mitochondria's involvement in many mechanisms identified...
Mitochondrial and Cellular Function in Fibroblasts, Induced Neurons, and Astrocytes Derived from Case Study Patients: Insights into Major Depression as a Mitochondria-Associated Disease.
The link between mitochondria and major depressive disorder (MDD) is increasingly evident, underscored both by mitochondria's involvement in many mechanisms identified in depression and the high prevalence of MDD in individuals with mitochondrial disorders. Mitochondrial functions and energy metabolism are increasingly considered to be involved in MDD's pathogenesis. This study focused on cellular and mitochondrial (dys)function in two atypical cases: an antidepressant non-responding MDD patient ("Non-R") and another with an unexplained mitochondrial disorder ("Mito"). Skin biopsies from these patients and controls were used to generate various cell types, including astrocytes and neurons, and cellular and mitochondrial functions were analyzed. Similarities were observed between the Mito patient and a broader MDD cohort, including decreased respiration and mitochondrial function. Conversely, the Non-R patient exhibited increased respiratory rates, mitochondrial calcium, and resting membrane potential. In conclusion, the Non-R patient's data offered a new perspective on MDD, suggesting a detrimental imbalance in mitochondrial and cellular processes, rather than simply reduced functions. Meanwhile, the Mito patient's data revealed the extensive effects of mitochondrial dysfunctions on cellular functions, potentially highlighting new MDD-associated impairments. Together, these case studies enhance our comprehension of MDD.
Topics: Humans; Depressive Disorder, Major; Astrocytes; Depression; Mitochondria; Neurons; Fibroblasts; Caricaceae; Mitomycin
PubMed: 38256041
DOI: 10.3390/ijms25020963 -
Applied and Environmental Microbiology Mar 1988The habitats for the two major Leptospira spp. differ. The main habitat of L. biflexa is soil and water, whereas L. interrogans primarily resides in the renal tubules of... (Comparative Study)
Comparative Study
The habitats for the two major Leptospira spp. differ. The main habitat of L. biflexa is soil and water, whereas L. interrogans primarily resides in the renal tubules of animals. We investigated whether these two species, along with L. illini (species incertae sedis), differ with respect to their sensitivity to UV radiation. The doses of UV resulting in 37, 10, and 1% survival were determined for representative serovars from each species. L. interrogans serovar pomona was 3.0 to 4.8 times more sensitive to UV than the other Leptospira species under the 37, 10, and 1% survival parameters. In comparison to other bacteria, L. interrogans serovar pomona is among the most sensitive to UV. In a qualitative UV sensitivity assay, L. interrogans serovars were found to be in general more sensitive than L. biflexa serovars. All three species were found to have a photoreactivation DNA repair mechanism. Since organisms that are resistant to UV are often resistant to the DNA cross-linking agent mitomycin C, we tested the relative sensitivity of several Leptospira serovars to this compound. With few exceptions, L. biflexa and L. illini serovars were considerably more resistant to mitomycin C than the L. interrogans serovars. The mitomycin C sensitivity assay could be a useful addition to current characterization tests used to differentiate the Leptospira species.
Topics: Dose-Response Relationship, Radiation; Drug Resistance, Microbial; Fresh Water; Leptospira; Leptospira interrogans; Mitomycin; Mitomycins; Species Specificity; Ultraviolet Rays; Water Microbiology
PubMed: 3132098
DOI: 10.1128/aem.54.3.728-733.1988 -
Asia-Pacific Journal of Ophthalmology... 2021Trabeculectomy with adjunctive use of Mitomycin C (MMC) has been a benchmark for glaucoma filtration surgery for decades. However, there are many variations in the ways...
Trabeculectomy with adjunctive use of Mitomycin C (MMC) has been a benchmark for glaucoma filtration surgery for decades. However, there are many variations in the ways that the sponges soaked with MMC are applied during the trabeculectomy surgery. We herein describe our way of placing the MMC-soaked sponges to improve the safety and efficacy of the trabeculectomy. The sponges are placed vertically and posteriorly with the long side of the sponge perpendicular to the limbus, not parallel. This will reduce the size of the conjunctival wound at the limbus to preserve more virgin conjunctiva that can be used for repeated trabeculectomy when needed. This will also facilitate a more posteriorly directed flow of aqueous drainage that, in turn, may increase the success rate of the trabeculectomy. We have obtained encouraging results in our practice, and further large-scale randomized studies seem warranted.
Topics: Glaucoma; Humans; Intraocular Pressure; Mitomycin; Trabeculectomy; Treatment Outcome
PubMed: 34608066
DOI: 10.1097/APO.0000000000000438 -
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