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Recurrent epithelial erosions develop in the cornea due to prior injury or genetic predisposition. Studies of recurrent erosions in animal models allow us to gain insight into how erosions form and are resolved. While slowing corneal epithelial cell migration and reducing their proliferation following treatment with mitomycin C reduce erosion formation in mice after sterile debridement injury, additional factors have been identified related to cytokine expression and immune cell activation. The relationship between recruitment of immune cells to the region of the cornea where erosions form and their potential roles in erosion formation and/or erosion repair remains unexplored in the C57BL/6 mouse recurrent erosion model. Here, high resolution imaging of mouse corneas was performed at D1, D7, and D28 after dulled-blade debridement injury in C57BL/6 mice. Around 50% of these mice have frank corneal erosions at D28 after wounding. A detailed assessment of corneas revealed the involvement of M2 macrophages in both frank and developing erosions at early stages of their formation. [ABSTRACT FROM AUTHOR]

Anamnesis: A descriptive series of six cases of dogs with glaucoma are presented comparing the fibrosis inhibition effect of three drugs used during trabeculectomy (TEC). Clinical findings: The patients were diagnosed with primary chronic closedangle glaucoma refractory to topical medical treatment with no pupillary light reflex and negative eyeblink response to threat and ocular pain. Therapeutic approach: Two patients received an intraoperative application of bevacizumab; two received 5-fluorouracil; and two, mitomycin C. Intraocular pressure (IOP) and filtering ampoule were observed on days 1, 7, 30, 60, and 90 post-surgery. Results and conclusion: Bevacizumab regulated IOP under 25 mmHg, constituting the drug of choice for dogs with primary closed-angle glaucoma without previous positive response to topical therapy and subjected to TEC, when compared with 5-fluorouracil and MMC regarding the inhibitory effect of fibrosis. [ABSTRACT FROM AUTHOR]

To measure the changes in treatment patterns for non-muscle invasive bladder cancer before and during the Bacillus Calmette-Guerin (BCG) drug shortage. We used a 5% random sample of Medicare beneficiaries and identified 7971 bladder cancer patients (2648 pre-BCG shortage and 5323 during the shortage) ≥66 years of age who received intravesical treatment within 1 year of diagnosis between 2010 and 2017. The BCG shortage period was defined from July 2012 ongoing. Full induction treatment with BCG, mitomycin C, gemcitabine, or other intravesical agents was defined as receiving ≥5 of 6 treatments within 60 days. State-level BCG use before and during the drug shortage was compared in US states reporting at least 50 patients in each period. Independent variables included year of index date, age, sex, race, rurality, and region of residence. BCG utilization rates decreased 5.9% in the shortage period (95% CI (−8.2%)-(−3.7%)). The proportion of patients that completed a full induction course of BCG decreased from 31.0% in the pre-shortage period to 27.6% in the shortage period (P =.002). 84% of reporting states (16 of 19) had decreased BCG utilization ranging between 5% and 36% compared to pre-shortage rates. During the BCG drug shortage, eligible bladder cancer patients were less likely to receive gold standard intravesical BCG with a large variation in treatment patterns between US states. [ABSTRACT FROM AUTHOR]

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Purpose: Ethanol and mitomycin C (MMC) are clinically used to treat corneal diseases such as LASEK and LASIK surgery. In this study, we investigated the effects of time-dependent alcohol and MMC in cultured rat limbal stem cells (LSCs) to determine the appropriate time for the use of this compound in the clinical setting. Methods: LSCs (N = 10 eyes) isolated from male Wistar rats were cultured and characterized; then, isolates were divided into three groups. One group was exposed to a 20% concentration of ethanol for 5, 10, 15, 20, 25, and 30 s, and cell viability was assessed one, three, and five days following ethanol exposure using an MTT assay. To investigate the effect of MMC, cells in the second group were treated with 0.02% MMC in various periods (i.e., 15 s, 30 s, 60 s, 90 s, and 120 s) and time-dependent responses of cultured LSCs were recorded. Cells in the third group were co-treated with ethanol and MMC; then, dose and time dependency was evaluated. Results: In comparison with the viable cells in the control group, ethanol markedly decreased the viability of cells in a time-dependent manner in days one and three. On day five, the viability of LSCs was improved significantly (p < 0.05) in comparison with day one. The number of viable progenitor cells was significantly decreased after MMC treatment in a time-dependent manner, as determined by the MTT assay (p < 0.001). The use of mitomycin, along with alcohol, decreased cell viability in all groups treated with ethanol + MMC compared to the control on days one, three, and five (p < 0.0001). Conclusions: Our findings suggest that ethanol and MMC reduced cell viability in cultured LSCs in a time-dependent manner. In addition, when LSCs were exposed to alcohol alone, they had a better recovery process within 5 days in comparison to when exposed to mitomycin alone or mitomycin + alcohol. [ABSTRACT FROM AUTHOR]

The main purpose of this study is to evaluate and understand the clinical profile of patients presenting to an Indian tertiary care referral centre with Laryngotracheal Stenosis (LTS) and also to emphasise on the outcomes after treatment in these patients. This is a prospective observational study conducted at a tertiary care referral centre which included 18 patients diagnosed with LTS. All patients were evaluated clinically and radiologically to evaluate the degree of stenosis, site and length of the stenotic segment involved, intervened surgical procedure, intraoperative and postoperative complications following the procedure were all documented and taken into consideration. The data collected was analysed. The most common etiological cause of LTS was post intubation (77.8%). 61.5% among the 13 intubated patients had a history of intubation for more than 10 days. 83.3% of the cases had stenosis at the level of the subglottis and cervical trachea level. Post intubational airway stenosis is the most common cause of LTS. A precise assessment of the laryngotracheal complex is the cornerstone of LTS management. The choice of treatment depends on the location, severity, and length of stenosis, as well as on the patient's comorbidities, history of previous interventions, and on the expertise of the surgical team. Application of topical Mitomycin c during surgery reduces the incidence of granulations. Close postoperative follow up for a long time and the necessity of more than one intervention improves results and can spare patients the morbidity and mortality associated with acute airway obstruction. [ABSTRACT FROM AUTHOR]

A viral shunt can occur when phages going through a lytic cycle, including lysogenic phages triggered by inducing agents (e.g. mitomycin C), results in host lysis and the release of cell constituents and virions. The impact of a viral shunt on the carbon, including methane cycle in soil systems is poorly understood. Here, we determined the effects of mitomycin C on the aerobic methanotrophs in a landfill cover soil. To an extent, our results support a mitomycin C-induced viral shunt, as indicated by the significantly higher viral-like particle (VLP) counts relative to bacteria, elevated nutrient concentrations (ammonium, succinate), and initially impaired microbial activities (methane uptake and microbial respiration) after mitomycin C addition. The trend in microbial activities at <2 days largely corresponded to the expression of the pmoA and 16S rRNA genes. Thereafter (>11 days), the active bacterial community composition significantly diverged in the mitomycin C-supplemented incubations, suggesting the differential impact of mitomycin C on the bacterial community. Collectively, we provide insight on the effects of mitomycin C, and potentially a viral shunt, on the bacteria in the soil environment. [ABSTRACT FROM AUTHOR]

Isolated from Streptomyces caespitosus, 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. [ABSTRACT FROM AUTHOR]

Results from HIVEC-II show no oncological benefit from chemohyperthermia over the control treatment. Adverse events following chemohyperthermia were low of grade and short-lived, although these patients were less likely to complete their treatment. Adjuvant intravesical chemotherapy following tumour resection is recommended for intermediate-risk non–muscle-invasive bladder cancer (NMIBC). To assess the efficacy and safety of adjuvant intravesical chemohyperthermia (CHT) for intermediate-risk NMIBC. HIVEC-II is an open-label, phase 2 randomised controlled trial of CHT versus chemotherapy alone in patients with intermediate-risk NMIBC recruited at 15 centres between May 2014 and December 2017 (ISRCTN 23639415). Randomisation was stratified by treating hospital. Patients were randomly assigned (1:1) to adjuvant CHT with mitomycin C at 43°C or to room-temperature mitomycin C (control). Both treatment arms received six weekly instillations of 40 mg of mitomycin C lasting for 60 min. The primary endpoint was 24-mo disease-free survival as determined via cystoscopy and urinary cytology. Analysis was by intention to treat. A total of 259 patients (131 CHT vs 128 control) were randomised. At 24 mo, 42 patients (32%) in the CHT group and 49 (38%) in the control group had experienced recurrence. Disease-free survival at 24 mo was 61% (95% confidence interval [CI] 51–69%) in the CHT arm and 60% (95% CI 50–68%) in the control arm (hazard ratio [HR] 0.92, 95% CI 0.62–1.37; log-rank p = 0.8). Progression-free survival was higher in the control arm (HR 3.44, 95% CI 1.09–10.82; log-rank p = 0.02) on intention-to-treat analysis but was not significantly higher on per-protocol analysis (HR 2.87, 95% CI 0.83–9.98; log-rank p = 0.06). Overall survival was similar (HR 2.55, 95% CI 0.77–8.40; log-rank p = 0.09). Patients undergoing CHT were less likely to complete their treatment (n =75, 59% vs n = 111, 89%). Adverse events were reported by 164 patients (87 CHT vs 77 control). Major (grade III) adverse events were rare (13 CHT vs 7 control). CHT cannot be recommended over chemotherapy alone for intermediate-risk NMIBC. Adverse events following CHT were of low grade and short-lived, although patients were less likely to complete their treatment. The HIVEC-II trial investigated the role of heated chemotherapy instillations in the bladder for treatment of intermediate-risk non–muscle-invasive bladder cancer. We found no cancer control benefit from heated chemotherapy instillations over room-temperature chemotherapy. Adverse events following heated chemotherapy were low grade and short-lived, although these patients were less likely to complete their treatment. [ABSTRACT FROM AUTHOR]

Introduction: Bleb scarring is the most important complication of trabeculectomy. Changing the application position of mitomycin C (MMC) during trabeculectomy might affect the surgery outcome. Our aim is to compare the effectiveness and safety of intraocular pressure (IOP) lowering in two different application sites of mitomycin in trabeculectomy. Methods: This retrospective trial compared the surgical outcomes of 177 eyes that underwent trabeculectomy with adjunctive mitomycin C. In 70 eyes, an MMC-soaked sponge was applied under the scleral flap without touching Tenon's capsule. In 107 eyes, an MMC-soaked sponge was applied under the scleral flap covered by Tenon's capsule. Outcome measures were the IOP, best-corrected visual acuity (BCVA), success rates, and incidence of complications. Results: Within both groups, a highly significant IOP reduction was seen during follow-up. The effectiveness in reducing IOP and the change in best-corrected visual acuity (BCVA) were similar between the two groups. Thin-walled blebs and postoperative hypotony were seen more often when MMC-soaked sponges were applied under the scleral flap covered by Tenon's capsule (P = 0.008 and P = 0.012, respectively). There was no significant difference in BCVA or other complications in either group. Conclusion: Since the effectiveness of IOP reduction was similar between both groups and with a low incidence of thin-walled blebs and hypotony, the subscleral application without touching Tenon's capsule seems to be the safer application site of MMC during trabeculectomy. [ABSTRACT FROM AUTHOR]

The effect of hydrogen peroxide, an antiseptic dental treatment, on Aggregatibacter actinomycetemcomitans, the main causative agent of localized invasive periodontitis, was investigated. Hydrogen peroxide treatment (0.06%, 4× minimum inhibitory concentration) resulted in the persistence and survival of approximately 0.5% of the bacterial population. The surviving bacteria did not genetically acquire hydrogen peroxide resistance but exhibited a known persister behavior. Sterilization with mitomycin C significantly reduced the number of A. actinomycetemcomitans persister survivors. RNA sequencing of hydrogen peroxide-treated A. actinomycetemcomitans showed elevated expression of Lsr family members, suggesting a strong involvement of autoinducer uptake. In this study, we found a risk of A. actinomycetemcomitans persister residual from hydrogen peroxide treatment and hypothesized associated genetic mechanisms of persister from RNA sequencing. [ABSTRACT FROM AUTHOR]

This prospective study aimed to evaluate the effectiveness of decellularized porcine conjunctiva (DPC) in the management of severe symblepharon. Sixteen patients with severe symblepharon were enrolled in this study. After symblepharon lysis and Mitomycin C (MMC) application, tarsus defects were covered with residual autologous conjunctiva (AC), autologous oral mucosa (AOM), or DPC throughout the fornix, and DPC was used for all the exposed sclera. The outcomes were classified as complete success, partial success, or failure. Six symblepharon patients had chemical burns and ten had thermal burns. Tarsus defects were covered with DPC, AC, and AOM in two, three, and eleven cases, respectively. After an average follow-up of 20.0 ± 6 months, the anatomical outcomes observed were complete successes in twelve (three with AC+DPC, four with AC+AOM+DPC, and five with AOM+DPC) (75%) cases, partial successes in three (one with AOM+DPC and two with DPC+DPC) (18.75%) cases, and failure in one (with AOM+DPC) (6.25%) case. Before surgery, the depth of the narrowest part of the conjunctival sac was 0.59 ± 0.76 mm (range, 0–2 mm), tear fluid quantity (Schirmer II tests) was 12.5 ± 2.26 mm (range, 10–16 mm), and the distance of the eye rotation toward the opposite direction of the symblepharon was 3.75 ± 1.39 mm (range, 2–7 mm). The fornix depths increased to 7.53 ± 1.64 mm (range, 3–9 mm), eye movement was significantly improved, and the distance of eye movement reaching 6.56 ± 1.24 mm (range, 4–8 mm) 1 month after the operation; the postoperative Schirmer II test (12.06 ± 2.90 mm, range, 6–17 mm) was similar to that before surgery. Goblet cells were finally found in fifteen patients by conjunctival impression cytology in the transplantation area of DPC, except for one patient who failed. DPC could be considered an alternative for ocular surface reconstruction of severe symblepharon. Covering tarsal defects with autologous mucosa is necessary for extensive reconstruction of the ocular surface. [ABSTRACT FROM AUTHOR]

Purpose: Resveratrol (RSV) is a natural polyphenol phytoalexin compound and has long been considered to possess antioxidant and anti-inflammatory effects. In order to exploit the protective potential of RSV in anterior segment diseases, we investigated the possible cytotoxic, genotoxic/antigenotoxic effects of human limbal explant cultures to RSV and MMC or H2O2 alone and in combination. Methods: A total of 18 limbal explant tissues obtained from three corneal donors were placed on the 12 well tissue culture polystyrene plates and cultured for 14 days. Cell growth from limbal explants was observed by inverted phase contrast microscopy. The cytotoxic effects of RSV was studied by neutral red uptake assay. For the assessment of the genotoxic and antigenotoxic effects, basic alkaline technique of comet assay was performed. Results: It was found that the concentrations of RSV up to 100 μM did not significantly affect the viability of outgrowth cells of limbal explant during 24 h exposure. When compared to negative control, all concentrations of RSV alone caused an increase in DNA strand breakage. Interestingly, 10 μg/mL MMC alone caused similar tail intensity and tail moment values with RSV alone. On the other hand, RSV treatment in all doses seemed to decrease the DNA damage induced by either H2O2 or MMC. Conclusion: RSV is an attractive natural compound for the purpose of oxidative stress reduction in ocular surface and can be utilized as a supplement to promote ocular surface regeneration in vivo. [ABSTRACT FROM AUTHOR]

Patients with peritoneal metastases (PM) of colorectal cancer have a very poor outcome. Intraperitoneal delivery of chemotherapy is the preferred route for PM treatment. The main limitation of the treatment options is the short residence time of the cytostatic, with subsequent short exposure of the cancer cells. To address this, a supramolecular hydrogel has been developed that allows both local and slow release of its encapsulated drug, mitomycin C (MMC) or cholesterol-conjugated MMC (cMMC), respectively. This experimental study investigates if drug delivery using this hydrogel improves the therapeutic efficacy against PM. PM was induced in WAG/Rij rats (n = 72) by intraperitoneally injecting syngeneic colon carcinoma cells (CC531) expressing luciferase. After seven days, animals received a single intraperitoneal injection with saline (n = 8), unloaded hydrogel (n = 12), free MMC (n = 13), free cMMC (n = 13), MMC-loaded hydrogel (n = 13), or cMMC-loaded hydrogel (n = 13). Primary outcome was overall survival with a maximum follow-up of 120 days. Intraperitoneal tumor development was non-invasive monitored via bioluminescence imaging. Sixty-one rats successfully underwent all study procedures and were included to assess therapeutic efficacy. After 120 days, the overall survival in the MMC-loaded hydrogel and free MMC group was 78% and 38%, respectively. A trend toward significance was found when comparing the survival curves of the MMC-loaded hydrogel and free MMC (p = 0.087). No survival benefit was found for the cMMC-loaded hydrogel compared to free cMMC. Treating PM with our MMC-loaded hydrogel, exhibiting prolonged MMC exposure, seems effective in improving survival compared to treatment with free MMC. [ABSTRACT FROM AUTHOR]

Aim To compare between the outcomes of cauterized conjunctival autograft (CA) with and without mitomycin C (MMC) in primary pterygium surgery. Patients and methods This prospective interventional comparative study included 50 eyes in 50 patients with primary pterygium. Patients were randomly assigned into two equal groups: group 1 underwent pterygium excision with cauterized CA fixation, and group 2 underwent pterygium excision with cauterized CA fixation and intraoperative application of 0.02% MMC for 3 min. All patients underwent a preoperative, first day, first week, first month, third month, and sixth month postoperative ophthalmic examination. Any intraoperative or postoperative complications were recorded. Primary outcomes were reported as incidence of recurrence and any major (sight threatening) complications. Secondary outcomes were reported as any minor complications. Results A total of 50 patients (28 males and 22 females, with male to female ratio 1 : 1.3) were included in this study. Complications encountered in our study included recurrence of pterygium, which occurred in one (4%) eye in group 1 and 0 eyes in group 2. Two (8%) eyes in group 1 versus one (4%) eye in group 2 showed subconjunctival hemorrhage, one (4%) eye in group 2 showed focal scleral thinning, and one (4%) eye in group 2 showed a corneal epithelial defect. There was no statistically significant difference between the two groups regarding the incidence of any complication (P>0.05). Conclusion Cauterized CA without MMC is a safe and effective procedure for the surgical treatment of primary pterygium. There was no added benefit to intraoperative MMC application.

Background Punctal stenosis is a progressive constriction of the puncta with resultant epiphora. One of the most effective treatment options is one- to four-snip punctoplasty with or without mitomycin C (MMC). Aim The aim of this study was to assess the effectiveness of intraoperative MMC in increasing the success rate of three-snip punctoplasty in cases of punctal stenosis. Patients and methods This is a nonrandomized interventional prospective comparative study that was conducted at the Department of Ophthalmology, Al-Hussein and Bab El Sheria Al-Azhar University Hospitals, Cairo, Egypt. It included 31 eyes of 18 patients who underwent three-snip punctoplasty. The patients were divided into two groups: group 1 (15 eyes), in which MMC was not used during surgery, and group 2 (16 eyes), in which MMC was used intraoperatively for 2 min. Complete ocular examinations were performed in all patients using the slit lamp. Punctal stenosis grading was done as follows: grade 0 (absent punctum), grade 1 (a membrane covering the papilla), grade 2 (less than average size, however, can be recognized), grade 3 (normal), grade 4 (small slit

PURPOSE: To develop a new dry eye syndrome (DES) animal model by injecting mitomycin C (MMC) into the lacrimal glands (LGs) of rabbits evaluated by clinical examinations. MATERIALS AND METHODS: A volume of 0.1 mL of MMC solution was injected in the LG and the infraorbital lobe of the accessory LG of rabbits for DES induction. Twenty male rabbits were separated into three groups, the control group, and different concentration of MMC, (MMC 0.25: 0.25 mg/mL or MMC 0.50: 0.5 mg/mL) were tested. Both MMC-treated groups received MMC twice injection on day 0 and day 7. Assessment of DES included changes in tear production (Schirmer's test), fluorescein staining pattern, conjunctival impression cytology, and corneal histological examination. RESULTS: After MMC injection, no obvious changes in the rabbit's eyes were noted by slit-lamp examination. Both the MMC 0.25 and the MMC 0.5 groups revealed decreased tear secretion after injection, and the MMC 0.25 group showed a continuous decrease in tear secretion up to 14 days. Fluorescent staining showed punctate keratopathy in both MMC-treated groups. In addition, both MMC-treated groups demonstrated decreased numbers of conjunctival goblet cells after injection. CONCLUSION: This model induced decreased tear production, punctate keratopathy, and decreased numbers of goblet cells, which are consistent with the current understanding of DES. Therefore, injecting MMC (0.25 mg/mL) into the LGs is an easy and reliable method to establish a rabbit DES model which can apply in new drug screening.

AIM: To determine the long-term postoperative outcomes of deep sclerectomy-trabeculectomy (DST) with mitomycin C (MMC) in the treatment of glaucoma. METHODS: Patients who underwent DST with MMC between 2010 and 2017 were included in this retrospective observational study. Complete success was defined as postoperative intraocular pressure (IOP) ≤21 mm Hg or 30% reduction of IOP from baseline without any topical IOP-lowering agent, and qualified success defined as IOP≤21 mm Hg or 30% reduction of IOP from baseline with/without single topical agent. We evaluated the surgical success rates and complication rates of this procedure, as well as described the IOP profiles, best corrected visual acuity (BCVA) profiles and mean deviations (MD) of Humphrey visual field (HVF) 24-2 performance at each follow-up time point. Mixed linear regression models were constructed to determine estimated predictive values of demographic data, use of topical IOP-lowering agents, baseline and postoperative IOP and optical profiles (e.g., BCVA and MD). RESULTS: Totally 98 eyes (mean postoperative follow-up 67.5mo) showed mean IOP reduction at every follow-up interval. Both median BCVA and MD of visual fields were maintained throughout the follow-up intervals when comparing to baseline. The number of IOP-lowering medications decreased from 2.8±0.8 to 0.3±0.7 (P=0.068). Totally 84 (85.7%) eyes achieved complete success at final follow-up. Transient hyphaema and transient choroidal effusion developed in 15 eyes (15.3%) and 11 eyes (11.2%) respectively. Other complications included shallow anterior chamber in 5 eyes (5.1%), bleb leak in 4 eyes (4.1%), bleb revision in 7 eyes (7.1%), bleb needling in 9 eyes (9.2%) and repeat trabeculectomy in 1 eye (1.0%). There was no endophthalmitis, blebitis or macular oedema. There was no significant correlation between postoperative IOP control and postoperative BCVA. CONCLUSION: DST with MMC demonstrates effective and sustained long-term outcomes in the treatment of glaucoma with no major complication.

Abstract Background Rho-kinase inhibitors can inhibit fibrosis after glaucoma surgery. This study aimed to evaluate the effect of rho-kinase inhibitor after needling procedure with mitomycin C for the failure of filtering bleb with trabeculectomy. Methods This retrospective single-center study examined the effects of rho-kinase inhibitor after the needling procedure. We included 27 eyes of 27 patients with glaucoma who underwent needling procedure using mitomycin C and were subsequently treated with ripasudil—a rho-associated protein kinase inhibitor (ripasudil group)—or without ripasudil (control group). The ripasudil and control groups were compared in terms of intraocular pressure (IOP) and the number of antiglaucoma medications. Success at 12 months after the needling procedure was defined as a > 20% decrease in IOP from the preoperative period without surgical reintervention. Results At 12 months after the needling procedure, the mean IOP decreased from 16.9 ± 4.5 to 12.6 ± 1.1 mmHg in the control group and from 16.0 ± 5.3 to 12.2 ± 1.2 mmHg in the ripasudil group (p = 0.77). The 12-month success rates were 60.00% and 56.25% in the control and ripasudil groups (p = 0.98), respectively. In the preoperative period, the numbers of antiglaucoma drugs were 0.27 ± 0.46 and 0.92 ± 0.91 in the control and ripasudil groups (p = 0.022), respectively, and at 12 months after the needling procedure, they were 1.07 ± 1.44 and 0.73 ± 1.10 (p = 0.52), respectively. Conclusions Treatment with ripasudil (a rho-associated protein kinase inhibitor) after the needling procedure with mitomycin C did not show better results than treatment with the mitomycin C needling procedure alone at 12 months after the procedure.

Abstract Background To compare the surgical outcomes and postoperative complications with and without Ologen collagen matrix augmentation during XEN gel stent implantation. Methods We retrospectively analyzed patients who underwent XEN gel stent implantation with an ab externo technique. The amount of intraocular pressure (IOP) reduction, percentage of postoperative complications and additional management, and surgical success defined as IOP reduction greater than 20% compared with the preoperative IOP measurement were compared between Ologen-augmented and non-augmented groups. Groups of patients who underwent XEN gel stent implantation alone and combined with phacoemulsification were analyzed separately. Results A total 103 eyes of 103 participants were included. Of those, 72 eyes underwent standalone XEN gel stent implantation: 42 eyes with Ologen augmentation (Oloxen group) and 30 eyes without Ologen augmentation (Xen group). Thirty-one eyes underwent XEN gel stent implantation with phacoemulsification: 19 eyes with Ologen augmentation (Phaco-Oloxen group) and 12 eyes without Ologen augmentation (PhacoXen group). The surgical success rate at six months postoperatively was not different between the Oloxen and Xen groups (56.4% vs 43.3%, P > 0.05) or between the Phaco-Oloxen group and PhacoXen group (57.9% vs 41.7%, P > 0.05). The prevalence of postoperative hypotony, 5-fluorouracil injections, use of anti-glaucoma medications, bleb needling, and additional glaucoma surgeries was not different between the Oloxen and Xen groups or between the Phaco-Oloxen and PhacoXen groups when assessed six months postoperatively. Conclusions All groups showed significant IOP reduction after XEN gel stent implantation, but there was no significant difference between the Ologen collagen matrix augmented and non-augmented groups in surgical outcomes.

Aim:Non-coding ribonucleic acid (RNA) activated by deoxyribonucleic acid (DNA) damage (NORAD) is a long non-coding RNA activated during DNA damage response. Accumulating evidence suggest that NORAD is overexpressed in human cancers and associated with the drug-induced chemoresistance. The present study aims to explore the possible role of long non-coding RNA NORAD during mitomycin C-related chemoresistance and mitomycin C-induced DNA damage response.Materials and Methods:In cell culture experiments, MDA-MB-231 breast cancer cells were used. MTT cell viability assay was used to determine the effects of mitomycin C on breast cancer cells and application dose was determined accordingly. For analysis of NORAD gene expression levels, quantitative real-time polymerase chain reaction method was used.Results:Mitomycin C was found to suppress cell viability of breast cancer cells in a dose-dependent manner and half-maximal inhibitory concentration was determined as 1.12 µg/mL (p

Introduction: DNA damage repair (DDR) is an essential process for living organisms and contributes to genome maintenance and evolution. DDR involves different pathways including Homologous recombination (HR), Nucleotide Excision Repair (NER) and Base excision repair (BER) for example. The activity of each pathway is revealed with particular drug inducing lesions, but the repair of most DNA lesions depends on concomitant or subsequent action of the multiple pathways. Methods: In the present study, we used two genotoxic antibiotics, mitomycin C (MMC) and Bleomycin (BLM), to decipher the interplays between these different pathways in E. coli. We combined genomic methods (TIS and Hi-SC2) and imaging assays with genetic dissections. Results: We demonstrate that only a small set of DDR proteins are common to the repair of the lesions induced by these two drugs. Among them, RecN, an SMC-like protein, plays an important role by controlling sister chromatids dynamics and genome morphology at different steps of the repair processes. We further demonstrate that RecN influence on sister chromatids dynamics is not equivalent during the processing of the lesions induced by the two drugs. We observed that RecN activity and stability requires a pre-processing of the MMC-induced lesions by the NER but not for BLM-induced lesions. Discussion: Those results show that RecN plays a major role in rescuing toxic intermediates generated by the BER pathway in addition to its well-known importance to the repair of double strand breaks by HR. [ABSTRACT FROM AUTHOR]

Purpose: To explore the visual field (VF) changes two years following augmented trabeculectomy. Methods: A retrospective study of patients who underwent augmented trabeculectomy surgery with mitomycin C by a single surgeon at East Lancashire Teaching Hospitals NHS Trust over 3 years. Patients with a minimum of two years postoperative follow-up were included. Baseline characteristics, intraocular pressure (IOP), VF, number of glaucoma medications, and complications were recorded. Results: In total, 206 eyes were included, 97 (47%) patients were female, and the mean age was 73.8 ± 10.3 (range 43 to 93) years. One hundred thirty-one (63.6%) eyes were pseudophakic before trabeculectomy. The patients were divided into three outcome groups according to VF outcome. Seventy-seven (37.4%) patients had stable VF, 35 (17.0%) patients showed VF improvement, and 94 (45.6%) had VF deterioration. The overall mean preoperative IOP was 22.7 ± 8.0 mmHg and postoperative IOP 10.4 ± 4.2 mmHg, with a reduction of 50.2% (P < 0.001). In total, 84.5% of postoperative patients did not require glaucoma medications. A higher number of patients with postoperative IOP ≥15 mmHg had deteriorating VF (P < 0.001). Based on preoperative MD distribution, VF improvement or stability was more achievable with patients with a preoperative VF defect up to -12 dB (n = 41, 59.4%) and in those with greater than -24 dB (n = 25, 64.1%). Conclusion: Trabeculectomy continues to be an effective means of lowering IOP in patients with uncontrolled glaucoma and is important in stabilizing or improving visual fields. We recommend early trabeculectomy to prevent further VF deterioration. This may help in maintaining VF for driving status and, thus, quality of life. [ABSTRACT FROM AUTHOR]

Purpose: Radical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course. Methods: Patients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested. Results: Of the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38 months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC. Conclusion: Combined treatment improved RFS and PFS only in patients with Ta disease. [ABSTRACT FROM AUTHOR]

Background: The high recurrence of a urethral stricture after direct vision internal urethrotomy (DVIU) has been a problem for years. Mitomycin C (MMC) is an excellent antifibrosis antigen that has been used in many fields, but its effect on a urethral stricture remains controversial. The purpose of this review was to investigate the effectiveness of MMC in reducing the recurrence rate of a urethral stricture after the first urethrotomy. Methods: Common databases were searched for publications prior to November 30, 2020. Randomized controlled and cohort trials were all included. Recurrence and success rates after the first urethrotomy of the posterior urethra were the main outcomes. Revman 5.3 was used for statistical analysis. Two evaluation systems, the Cochrane risk of bias tool and the Newcastle Ottawa Scale, were used to examine the risk of bias for RCTs and all studies. The quality of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation standard. Results: Sixteen trials were included, the reporting quality of which was generally poor, and the evidence level was very low to moderate. The addition of MMC could significantly reduce the recurrence rate of urethral strictures (risk ratio [RR] = 0.42; 95% confidence interval [CI]: 0.26, 0.67; p = 0.0002; 9 trials; 550 participants). The results of the subgroup analysis suggested that the effect of MMC combined with DVIU was significant in short (≤2 cm) anterior urethral strictures (RR = 0.39; 95% CI: 0.20, 0.78; p = 0.008), >12-month follow-up (RR = 0.45; 95% CI: 0.26, 0.76; p = 0.003). It also increased the success rate of the first urethrotomy procedure for posterior urethral contracture (RR = 0.74; 95% CI: 0.65, 0.84; p < 0.00001; 7 trials; 342 participants). Low-dose local injection of MMC was the most commonly used method. Conclusion: MMC combined with DVIU is a promising way to reduce the long-term recurrence rate of a short-segment anterior urethral stricture. It also increases the success rate of the first urethrotomy of the posterior urethra. However, more high-quality randomized controlled trials are needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the efficacy and safety of the PreserFlo MicroShunt (Santen, Osaka, Japan) in lowering intraocular pressure (IOP) in childhood glaucoma patients with previous failed glaucoma surgeries. Methods: This is a prospective case review of consecutive PreserFlo procedures performed in childhood glaucoma patients after failed surgeries. Age, sex, diagnosis, and previous glaucoma surgeries, as well as visual acuity, IOP, and treatment in the preoperative visit and all follow-up visits were collected. Outcome measures included IOP reduction from baseline, mean IOP change from baseline at month 6, medication use at 6 months, complications, adverse events, and need for further procedures. Results: Fourteen patients were included, 8 (57%) males and 6 (43%) females; the mean age was 27.5 ± 13.5 years. Nine patients (64%) had at least two trabeculectomies, and 6 patients (43%) had at least one trabeculectomy and a glaucoma drainage implant. The mean IOP change from baseline was 11.3 ± 4.9 mmHg at 12 months. At 12 months, 12 patients (86%) presented ≥ 20% IOP lowering from baseline, and 11 patients (79%) presented ≥ 30%. The mean medication count decreased from 3.9 ± 0.7 (baseline) to 0.7 ± 1.3 (12 months). No intraoperative complications were reported. No adverse events were noted. No secondary filtration surgery was required, although bleb needling was required in one case, 1 month after the surgery. Conclusions: PreserFlo with MMC can be used successfully to treat uncontrolled IOP in childhood glaucoma cases with previous failed surgeries. Larger studies with longer follow-up are needed to further explore the role of the device in resistant childhood glaucoma cases. [ABSTRACT FROM AUTHOR]

Intra-operative use of mitomycin C during glaucoma filtering surgeries is common surgical practice. Although postoperative complications of mitomycin C have been described, there are few reports of profound posterior segment toxicity. In this case report, we described a case of retinal toxicity following presumed inadvertent intraocular injection of mitomycin C during routine trabeculectomy. Purpose: To describe a case of postoperative retinal toxicity following the use of mitomycin C during a routine trabeculectomy. Methods: Case report of a single patient who underwent complete ophthalmic examination and multimodal imaging, including color fundus photos, optical coherence tomography, fundus autofluorescence, and fluorescein angiography. The study was declared exempt by the Institutional Review Board of Northwestern University. This research followed the tenets of the Declaration of Helsinki. Results: The patient developed profound vision loss and retinal damage during the postoperative course. Posterior segment findings include loss of vascular perfusion, diffuse loss of the outer, then inner, retinal layers, and subsequent total retinal detachment. Conclusion: Although mitomycin C is commonly used in glaucoma filtering surgeries, reports of postoperative posterior segment toxicity are rare. The etiology of postoperative toxicity in this case is probable inadvertent intraocular injection of mitomycin C. [ABSTRACT FROM AUTHOR]

Staphylococcus (S.) aureus colonizes up to 30% of all humans and can occasionally cause serious infections. It is not restricted to humans as it can also often be found in livestock and wildlife. Recent studies have shown that wildlife strains of S. aureus usually belong to other clonal complexes than human strains and that they might differ significantly with regard to the prevalence of genes encoding antimicrobial resistance properties and virulence factors. Here, we describe a strain of S. aureus isolated from a European badger (Meles meles). For molecular characterisation, DNA microarray-based technology was combined with various next-generation sequencing (NGS) methods. Bacteriophages from this isolate were induced with Mitomycin C and characterized in detail by transmission electron microscopy (TEM) and NGS. The S. aureus isolate belonged to ST425 and had a novel spa repeat sequence (t20845). It did not carry any resistance genes. The uncommon enterotoxin gene see was detected in one of its three temperate bacteriophages. It was possible to demonstrate the induction of all three prophages, although only one of them was expected to be capable of excision based on its carriage of the excisionase gene xis. All three bacteriophages belonged to the family Siphoviridae. Minor differences in size and shape of their heads were noted in TEM images. The results highlight the ability of S. aureus to colonize or infect different host species successfully, which can be attributed to a variety of virulence factors on mobile genetic elements, such as bacteriophages. As shown in the strain described herein, temperate bacteriophages not only contribute to the fitness of their staphylococcal host by transferring virulence factors, but also increase mobility among themselves by sharing genes for excision and mobilization with other prophages. [ABSTRACT FROM AUTHOR]

This retrospective, single-center study evaluates the safety and efficacy of PreserfloTM MicroShunt (MicroShunt) implantations compared to trabeculectomies (TETs) in patients diagnosed with pseudoexfoliation glaucoma (PEXG). A total of 31 eyes from 28 patients received a MicroShunt implantation, and 29 eyes from 26 patients received a TET. Surgical success was defined as an intraocular pressure (IOP) between 5 mmHg and 17 mmHg at the end of the follow-up period, no need for surgical revisions or secondary glaucoma surgery, and no loss of light perception. In the MicroShunt group, the mean IOP dropped from 20.8 ± 5.9 mmHg at baseline to 12.4 ± 2.8 mmHg (p < 0.0001) after one year. In the TET group, the mean IOP dropped from 22.3 ± 6.5 mmHg to 11.1 ± 3.7 mmHg (p < 0.0001) after 12 months. In both of the groups, the mean number of medications was reduced significantly (MicroShunt from 2.7 ± 1.2 to 0.2 ± 0.7; p < 0.0001 vs. TET from 2.9 ± 1.2 to 0.3 ± 0.9; p < 0.0001). Considering the success rates, 83.9% of the MicroShunt eyes achieved complete success, and 90.3% qualified for success at the end of the follow-up period. In the TET group, the rates were 82.8% and 93.1%, respectively. The postoperative complications were comparable between both groups. In conclusion, the MicroShunt implantation demonstrated non-inferiority regarding its efficacy and safety profile compared to TET in PEXG at a follow-up of one year. [ABSTRACT FROM AUTHOR]

Post-surgical scarring is a known cause of trabeculectomy failure. The aim of this study was to investigate the effectiveness of ranibizumab as an adjuvant anti-scarring agent in experimental trabeculectomy. Forty New Zealand white rabbits were randomised into four eye treatment groups: groups A (control), B (ranibizumab 0.5 mg/mL), C (mitomycin C [MMC] 0.4 mg/mL), and D (ranibizumab 0.5 mg/mL and MMC 0.4 mg/mL). Modified trabeculectomy was performed. Clinical parameters were assessed on post-operative days 1, 2, 3, 7, 14, and 21. Twenty rabbits were euthanised on day 7, and the other twenty were euthanised on day 21. Eye tissue samples were obtained from the rabbits and stained with haematoxylin and eosin (H&E). All treatment groups showed a significant difference in IOP reduction compared with group A (p < 0.05). Groups C and D showed a significant difference in bleb status on days 7 (p = 0.001) and 21 (p = 0.002) relative to group A. H&E staining showed significantly low fibrotic activity (p < 0.001) in group C on both days and inflammatory cell grade in group B on day 7 (p < 0.001). The grade for new vessel formation was significantly low in groups B and D on day 7 (p < 0.001) and in group D on day 21 (p = 0.007). Ranibizumab plays a role in reducing scarring, and a single application of the ranibizumab–MMC combination showed a moderate wound-modulating effect in the early post-operative phase. [ABSTRACT FROM AUTHOR]

Background: Non-muscle invasive bladder cancer (NMIBC) is characterized by a high rate of recurrence and progression, despite surgery and adjuvant therapies.Objective: To analyze the published results on the effectiveness of mitomycin C (MMC) applied with an electromotive drug administration device (EMDA) in the treatment of patients with non-muscle invasive bladder tumors.Method: A systematic review was conducted using the PubMed and Google Scholar search platforms. We selected the studies that included the recurrence and/or progression rates or complete response rate in patients diagnosed with NMIBC according to their treatment and included MMC applied with EMDA. The last search was performed in November 2021.Results: The search yielded 64 articles; 11 articles met the selection criteria. In two of the 11 selected articles, mitomycin C was applied with an EMDA device (MMC-EMDA) as an ablative treatment, avoiding surgery in 50% of the patients. In 1 of the 11 studies, the application of MMC-EMDA was used as an induction treatment using a single preoperative instillation with promising results. In the remaining 8 studies, adjuvant MMC was applied with the EMDA device; in 3 of these 8 cases, treatment with MMC-EMDA alone was applied initially. In another3 cases the same treatment was applied after nonresponse to bacillus Calmette Guerin (BCG), and in the last 2 studies, MMC-EMDA was applied in combination with the classic therapy (BCG). All the studies selected supported the efficacy and safety of MMC-EMDA in patients with intermediate and high- risk bladder cancer. In 3 studies, adjuvant therapy with MMC-EMDA was performed in nonresponders to BCG, finding that adjuvant therapy with MMC-EMDA applied to BCG nonresponders without CIS avoided or delayed surgery.Conclusions: The application of EMDA-enhanced MMC has been studied at different times of disease and with different administration protocols. It appears to delay bladder tumor recurrence and progression in certain populations. However, the methodological limitations of the published studies prevent definitive conclusions about its efficacy. [ABSTRACT FROM AUTHOR]

HMG-CoA reductase inhibitors (statins) are widely used in the therapy of atherosclerosis and have a number of pleiotropic effects, including DNA repair regulation. We studied the cytogenetic damage and the expression of DNA repair genes (DDB1, ERCC4, and ERCC5) in human coronary artery (HCAEC) and internal thoracic artery endothelial cells (HITAEC) in vitro exposed to mitomycin C (MMC) (positive control), MMC and atorvastatin (MMC+Atv), MMC followed by atorvastatin treatment (MMC/Atv) and 0.9% NaCl (negative control). MMC/Atv treated HCAEC were characterized by significantly decreased micronuclei (MN) frequency compared to the MMC+Atv group and increased nucleoplasmic bridges (NPBs) frequency compared to both MMC+Atv treated cells and positive control; DDB1, ERCC4, and ERCC5 genes were upregulated in MMC+Atv and MMC/Atv treated HCAEC in comparison with the positive control. MMC+Atv treated HITAEC were characterized by reduced MN frequency compared to positive control and decreased NPBs frequency in comparison with both the positive control and MMC/Atv group. Nuclear buds (NBUDs) frequency was significantly lower in MMC/Atv treated cells than in the positive control. The DDB1 gene was downregulated in the MMC+Atv group compared to the positive control, and the ERCC5 gene was upregulated in MMC/Atv group compared to both the positive control and MMC+Atv group. We propose that atorvastatin can modulate the DNA damage repair response in primary human endothelial cells exposed to MMC in a cell line- and incubation scheme-dependent manner that can be extremely important for understanding the fundamental aspects of pleoitropic action of atorvastatin and can also be used to correct the therapy of patients with atherosclerosis characterized by a high genotoxic load. [ABSTRACT FROM AUTHOR]

Purpose: To show the effect of a 6-month (4 times weekly followed by 5 times monthly) maintenance mitomycin C regimen on the prevention of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods: A total of 119 patients undergoing a RNU between 2007 and 2021 in a single center hospital were retrospectively reviewed. A total of 66 patients were eligible for further analysis. 27 patients received no post-operative MMC (median follow-up: 110 months) and 39 patients received a 6-month (4 times weekly, 5 times monthly) maintenance regimen of MMC (median follow up: 48 months). The primary outcome was the 1-, 2- and 5-year bladder recurrence free survival (BRFS). Results: There was a significant difference (p = 0.001) in BRFS between the two groups. The 1-, 2, and 5-year BRFS for the MMC− group was 67%, 63% and 43%, respectively. The 1-, 2- and 5-year BRFS for the MMC + group was 95%, 86% and 86%, respectively. Univariate analysis showed no other potential prognostic factors that had a significant effect on the BRFS. Conclusion: A 6-month maintenance schedule of MMC is effective at significantly reducing the risk of IVR after RNU for UTUC. We could not find any other significant prognostic factors to predict IVR. [ABSTRACT FROM AUTHOR]

In this work, microscale poly-2-hydroxyethyl methacrylate [p(HEMA)]-based cryogels were fabricated as a drug delivery material using molecular imprinting technology for controlled release of mitomycin C (MMC) as an anti-cancer drug. MMC imprinted pHEMA-based micro cryogels (pMIPs) were prepared according to free-radical polymerization by using N-methacryloyl-(l)-histidine methyl ester (MAH) as an amino-acid-based polymerizable functional monomer using a micro stencil array chip with microwells of 200 μm diameter and 500 μm thickness. Following that, scanning electron microscope, swelling test, and Fourier Transform Infrared Spectroscopy were used for the characterization studies of pMIPs. After the characterization studies, MMC release performance of pMIPs was investigated towards the different pH values and various MMC concentrations in the aqueous solutions. The in vitro cytotoxicity studies of the pMIPs and the non-imprinted pHEMA based micro cryogels (pNIPs) were examined using L929 cell line. According to the experimental findings, the incorporation of MAH monomer could increase the release performance of pMIPs and the release of MMC from the pMIPs was non-Fickian in the aqueous solution. pMIPs did not show any noticeable cytotoxicity and could be potentially used as a new drug carrier for MMC release. [ABSTRACT FROM AUTHOR]

Purpose: We retrospectively investigated the widely used radiosensitisers cisplatin and mitomycin C/5-fluorouracil (5-FU) in patients with locally advanced vulvar cancer for outcome and toxicity. Methods: We screened the archive for patients treated with chemoradiation for vulvar cancer diagnosed between 01/2010 and 08/2021 at our institution. The impact of both radiosensitisers on prognosis was compared using Kaplan–Meier method and Cox-regression analysis. Results: One hundred and forty-three patients with vulvar cancer were screened. Twenty-nine patients received chemoradiation (mitomycin C/5-FU n = 14; cisplatin n = 12; others n = 3) as a primary, neoadjuvant or adjuvant treatment. Median follow-up was 15.5 months. Patients in the cisplatin group were older (mean age 54.4 vs. 70.7; p = 0.004). However, the mitomycin C/5-FU group had more advanced tumour stages. The 2-year recurrence-free survival (RFS) was comparable (44.5% vs. 33.3%; p = 0.932). The 2-year overall survival (OS) showed a numerical but not statistically significant difference in favour of the mitomycin C/5-FU group (59.7% vs. 31.7%; p = 0.37). 64.3% (9 out of 14) patients, who received mitomycin C/5-FU achieved clinical complete response (cCR) compared to 41.7% (5 out of 12) who received cisplatin (p = 0.505). Radiodermatitis was the most common adverse event in both groups (81%) and more severe in the mitomycin C/5-FU cohort. Myelotoxicity was frequently observed in both groups. Eighteen patients received an additional radiation boost with 10.0 (9–16) Gy and showed a significantly prolonged RFS (p = 0.027) and OS (p = 0.003). Conclusion: Mitomycin C/5-FU may be considered in the treatment of young and healthy patients with locally advanced vulvar cancer. [ABSTRACT FROM AUTHOR]

Purpose To assess the long-term outcome of Stab incision glaucoma surgery (SIGS) and compare it with subscleral trabeculectomy (SST) in the management of open-angle glaucoma (OAG). Methods Twenty eyes of 20 OAG patients were randomly assigned into group 1: 10 patients underwent SIGS + Mitomycin C (MMC), and group 2: 10 patients underwent SST + MMC. The patients were followed-up over 2 years after surgery. Our outcome measures were: Postoperative intraocular pressure IOP, number of medications used, and postoperative complications. Results Twenty-four months postoperatively, the mean IOP was 13.78±2.05 mmHg in the SIGS group compared with preoperative IOP of 26.33±5.1 mmHg (P <0.001, paired t-test), and 14.38±4.56 mmHg in SST group compared with preoperative IOP of 30.13±7.51 mmHg (P <0.001, paired t-test). No significant differences in mean IOP between groups either preoperatively (P=0.15) or along follow-up (P=0.62 at last visit). The mean IOP drop from baseline was 12.56±5.00 mmHg (46.33±10.50%) in SIGS group and 15.75±8.22 mmHg (49.50±17.95%) in SST group (P=0.26). A significant decrease in the number of glaucoma medications was noted in the SIGSS group (P <0.001), in the SST group, the number decreased but was not statistically significant (P =0.120). Conclusion SIGS is comparable with SST in achieving long-term significant and maintained IOP reduction over up to 2 years, in addition to decreasing the number of antiglaucoma medications postoperatively. SIGS is recommended for surgical management of primary OAG as it has the advantage of being a faster, easier, less traumatic alternative to conventional SST with fewer complications. [ABSTRACT FROM AUTHOR]

Purpose: We herein compare topical interferon alpha 2b (IFN-α2b) to topical mitomycin C (MMC) in the adjuvant management after excision of primary acquired melanosis with atypia (PAM) and melanoma of the conjunctiva/cornea (CM). Methods: We included 25 tumors from 25 patients (six with PAM and 19 with CM). After surgical excision, four patients started with adjuvant IFN-α2b (two in combination with radiotherapy), 19 with MMC, and two with radiotherapy alone. Five patients were switched from initial MMC/radiotherapy to IFN-α2b during follow-up. Efficacy was assessed via time to tumor recurrence and initial therapy response. Results: With initial IFN-α2b, three patients (3/4, two with additional radiotherapy) showed complete remission (follow-up: 1478–1750 days) and one recurrence (1/4) was noted after 492 days. With initial MMC, no recurrence was recorded in 15 of the 19 patients (follow-up: 99–4732 days). Five patients were switched from MMC or radiotherapy to IFN-α2b: two patients showed complete remission (2/5), while another two (2/5) experienced recurrences and remained without recurrence after repeated courses of IFN-α2b (follow-up: 1798 and 1973 days). Only one patient showed incomplete response. Adverse effects were recorded in five patients, all received MMC. Conclusion: Topical IFN-α2b (arguably together with radiotherapy) may be a viable alternative to MMC in PAM and CM. We observed fewer side effects at similar response rates. However, when response to MMC was poor, IFN-α2b may also be of limited utility. [ABSTRACT FROM AUTHOR]

This study investigated the beneficial properties of prickly pear peel (PPP) extracts from Opuntia ficus-indica (L.) Mill. Extracts were obtained via the Soxhlet extraction method using methanol (P1), ethanol (P2) and ethanol-water (P3) as extraction solvents. Their total phenolic and flavonoid content (TPC and TFC, respectively) and their antioxidant activity (AA) were determined. The PPP extracts were characterized in detail using mass spectrometry techniques. Their cyto-genotoxic effect and antigenotoxic potential against mitomycin C were evaluated via the cytokinesis block micronucleus (CBMN) assay on human lymphocytes. Enhanced TPC, TFC and AA values were recorded for all the extracts. Moreover, P1 and P2 were cytotoxic only at the highest concentrations, whereas P3 was found to be cytotoxic in all cases. No significant micronucleus induction was observed in the tested extracts. The PPP extracts contain bioactive compounds such as flavonoids, carboxylic acids, alkaloids, fatty acids and minerals (mainly K, Si, Mg, Ca, P and Zn). The results showed that all three extracts exerted high antigenotoxic activity. Our findings confirm the beneficial and genoprotective properties of PPP extracts and further studies on the bioactive compounds of Opuntia ficus-indica (L.) Mill. are recommended, as it constitutes a promising plant in pharmaceutical applications. [ABSTRACT FROM AUTHOR]

The SOS response is a conserved stress response pathway that is triggered by DNA damage in the bacterial cell. Activation of this pathway can, in turn, cause the rapid appearance of new mutations, sometimes called hypermutation. We compared the ability of various SOS-inducing drugs to trigger the expression of RecA, cause hypermutation, and produce elongation of bacteria. During this study, we discovered that these SOS phenotypes were accompanied by the release of large amounts of DNA into the extracellular medium. The release of DNA was accompanied by a form of bacterial aggregation in which the bacteria became tightly enmeshed in DNA. We hypothesize that DNA release triggered by SOS-inducing drugs could promote the horizontal transfer of antibiotic resistance genes by transformation or by conjugation. [ABSTRACT FROM AUTHOR]

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Anti-neoplastic effect of DNA cross-linking agents such as cisplatin, mitomycin C, and psoralen is attributed to their ability to induce DNA interstrand cross-links (ICLs), which block replication, transcription, and linear repair pathways by preventing DNA strand separation and trigger apoptosis. It is generally agreed that the Fanconi anemia (FA) pathway orchestrates the removal of ICLs by the combined actions of various DNA repair pathways. Recently, attention has been focused on the ability of the NEIL3-initiated base excision repair pathway to resolve psoralen- and abasic site-induced ICLs in an FA-independent manner. Intriguingly, overexpression of NEIL3 is associated with chemo-resistance and poor prognosis in many solid tumors. Here, using loss- and gain-of-function approaches, we demonstrate that NEIL3 confers resistance to cisplatin and participates in the removal of cisplatin–DNA adducts. Proteomic studies reveal that the NEIL3 protein interacts with the 26S proteasome in a cisplatin-dependent manner. NEIL3 mediates proteasomal degradation of WRNIP1, a protein involved in the early step of ICL repair. We propose that NEIL3 participates in the repair of ICL-stalled replication fork by recruitment of the proteasome to ensure a timely transition from lesion recognition to repair via the degradation of early-step vanguard proteins. [ABSTRACT FROM AUTHOR]

Background: Bioprospecting of actinobacteria isolated from Kubuqi desert, China for antibacterial, antifungal and cytotoxic metabolites production and their structure elucidation. Results: A total of 100 actinobacteria strains were selectively isolated from Kubuqi desert, Inner Mongolia, China. The taxonomic characterization revealed Streptomyces as the predominant genus comprising 37 different species, along with the rare actinobacterial genus Lentzea. The methanolic extracts of 60.8% of strains exhibited potent antimicrobial activities against Staphylococcus aureus, Micrococcus luteus, Bacillus subtilis, Escherichia coli, Salmonella enterica, Saccharomyces cerevisiae and high to mild in vitro cytotoxicity against PC3 (prostate cancer) and A549 (lung carcinoma) cell lines. The metabolomics analysis by TLC, HPLC-UV/vis, HPLC-MS and NMR showed the presence of compounds with molecular weights ranging from 100 to 1000 Da. The scale-up fermentation of the prioritized anti-Gram-negative strain PU-KB10–4 (Streptomyces griseoviridis), yielded three pure compounds including; griseoviridin (1; 42.0 mgL− 1) with 20 fold increased production as compared to previous reports and its crystal structure as monohydrate form is herein reported for the first time, mitomycin C (2; 0.3 mgL− 1) and a new bacterial metabolite 4-hydroxycinnamide (3; 0.59 mgL− 1). Conclusions: This is the first report of the bioprospecting and exploration of actinobacteria from Kubuqi desert and the metabolite 4-hydroxycinnamide (3) is first time isolated from a bacterial source. This study demonstrated that actinobacteria from Kubuqi desert are a potential source of novel bioactive natural products. Underexplored harsh environments like the Kubuqi desert may harbor a wider diversity of actinobacteria, particularly Streptomyces, which produce unique metabolites and are an intriguing source to develop medicinally valuable natural products. [ABSTRACT FROM AUTHOR]

The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN-SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation-enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin-4, indicates the opening of tight junction. Moreover, MSN-SH(E)-associated reprogramming of M2 macrophages to M1-like phenotype is observed in vitro. The antitumor activity of the mitomycin C (MMC)-loaded nanovector (MMC@MSN-SH(E)) is more effective than that of MMC alone in both in vitro and in vivo. In addition, IHC staining is used to analyze IFN-y, TGF-/1, and TNF-a. These observations substantiated the significance of MMC@MSN-SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non-muscle invasive bladder cancer (NMIBC) dueto its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the characteristics of sustained drug release systems established by an arginine-glycine-aspartic acid (RGD) peptide hydrogel and mitomycin C (MMC) in vitro, and verify their antiscar effects in rat ocular injury model. Methods: Low, medium, and high loading doses of MMC were added to 5 mL 0.25%, 0.5%, and 1% wt RGD peptide hydrogel, respectively, to prepare 9 ratios of MMC-RGD systems. Drug release characteristics of the systems in phosphate-buffered saline solution were investigated by plotting the drug release curves and fitting them with mathematical models in OriginPro8.0 software. Appropriate ratios of MMC-RGD systems were selected as treatment in rat ocular injury model. Scar formation was observed by Masson staining and immunohistochemical staining with alpha-smooth muscle actin (α-SMA) and fibronectin (FN). Results: Nine ratios of MMC-RGD systems could release drug slowly. The maximum drug release proportions of all systems were >80%, and the time to maximum release proportions statistically prolonged with the increase of drug loading. Fitting with mathematical models indicated that the mechanisms of drug release were mainly Fick diffusion at early stage and Anomalous Transport at later stage. Systems of 1% wt RGD hydrogel were evaluated in animal experiments, which could inhibit hyperplasia of collagen and expression of α-SMA and FN. Conclusions: The RGD peptide hydrogel could be used as the carrier of MMC to establish sustained drug release system, which could inhibit scar formation after rat's ocular injury. [ABSTRACT FROM AUTHOR]