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Microbiology Spectrum Dec 2022Multidrug-resistant tuberculosis (MDR-TB) is often associated with poor clinical outcomes. In this study, we evaluated the potential of nosiheptide (NOS) as a new drug...
Multidrug-resistant tuberculosis (MDR-TB) is often associated with poor clinical outcomes. In this study, we evaluated the potential of nosiheptide (NOS) as a new drug candidate for treating Mycobacterium tuberculosis infections, including MDR-TB. The antimicrobial susceptibility testing was performed to determine the MICs of NOS against 18 reference strains of slowly growing mycobacteria (SGM) and 128 clinical isolates of M. tuberculosis. The postantibiotic effects (PAE) and interaction with other antituberculosis drugs of NOS were also evaluated using M. tuberculosis H37Rv. Fifteen out of the 18 tested reference strains of SGM had MICs far below 1 μg/mL. From the 128 M. tuberculosis clinical isolates, the MIC and MIC were 0.25 μg/mL and 1 μg/mL, respectively; the tentative epidemiological cutoff (ECOFF) was defined at 1 μg/mL. Furthermore, a Lys89Thr mutation was found in one M. tuberculosis isolate with a MIC of NOS >8 μg/mL. After 24 h of incubation, NOS at 1 μg/mL inhibited 25.79 ± 1.22% of intracellular bacterial growth, which was comparable with the inhibitory rate of 25.71 ± 3.67% achieved by rifampin at 2 μg/mL. Compared to rifampicin and isoniazid (INH), NOS had a much longer PAE, i.e., a value of about 16 days. In addition, a partial synergy between NOS and INH was observed. NOS has potent inhibitory activities against M. tuberculosis as well as in macrophages. Furthermore, the long PAE and partial synergistic effect with INH, in addition to the added safety of long-term use as a feed additive in husbandry, provide support for NOS being a promising drug candidate for tuberculosis treatment. This study is aimed at chemotherapy for MDR-TB, mainly to explore the anti-TB activity of the existing chemotherapeutic reagent. We found that NOS has potent inhibitory activities against M. tuberculosis regardless of the drug-resistant profile. Furthermore, NOS also showed the long PAE and partial synergistic effect with INH and is nontoxic, providing support for its promise as a drug candidate for drug-resistant tuberculosis treatment.
Topics: Humans; Mycobacterium tuberculosis; Antitubercular Agents; Isoniazid; Tuberculosis, Multidrug-Resistant; Rifampin; Microbial Sensitivity Tests; Mitomycin
PubMed: 36222690
DOI: 10.1128/spectrum.01444-22 -
Arquivos Brasileiros de Oftalmologia 2014
Topics: Glaucoma Drainage Implants; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Mitomycin; Trabeculectomy
PubMed: 25295896
DOI: 10.5935/0004-2749.20140035 -
Chemical Reviews Aug 2013
Review
Topics: Chemistry Techniques, Synthetic; Drug Resistance, Bacterial; Mitomycin; Mitomycins; Oxazines; Streptomyces
PubMed: 23654296
DOI: 10.1021/cr3001059 -
The Journal of Antibiotics Apr 1986The unstability of neocarzinostatin (NCS), apo-NCS and NCS-chromophore (NCS-chr) has been investigated by using an extra-weak chemiluminescence (CL) analyzer. A...
The unstability of neocarzinostatin (NCS), apo-NCS and NCS-chromophore (NCS-chr) has been investigated by using an extra-weak chemiluminescence (CL) analyzer. A significantly high emission intensity (10,840 counts/10 seconds) was detected from NCS under dark conditions at 20 degrees C, while no significant emission was observed in other antitumor antibiotics, such as, mitomycin C and pepleomycin. This high emission intensity of NCS was due to NCS-chr I (epoxide form) but not apo-NCS. The functional group generating the high extra-weak CL of NCS-chr I is probably the epoxide in the molecule, since the emission intensity of NCS-chr I (epoxide form) is much higher than that of NCS-chr II (hydrochloride adduct form). The extra-weak CL emission of NCS decreased under a nitrogen atmosphere and it was greatly enhanced under an oxygen atmosphere. The spectral analysis of NCS showed emission peaks around 460 and 570 nm. These observations strongly suggest that one of the emission species of NCS-chr may be due to singlet oxygen.
Topics: Antibiotics, Antineoplastic; Bleomycin; Drug Stability; Enediynes; Luminescent Measurements; Mitomycin; Mitomycins; Peplomycin; Powders; Spectrophotometry; Structure-Activity Relationship; Zinostatin
PubMed: 2423490
DOI: 10.7164/antibiotics.39.535 -
The British Journal of Ophthalmology Jul 2006Multicentre international cooperation would facilitate evaluations of both treatment efficacy and side effects
Multicentre international cooperation would facilitate evaluations of both treatment efficacy and side effects
Topics: Administration, Topical; Antibiotics, Antineoplastic; Conjunctival Neoplasms; Corneal Diseases; Drug Administration Schedule; Humans; Mitomycin; Patient Selection; Treatment Outcome
PubMed: 16782942
DOI: 10.1136/bjo.2006.092734 -
International Journal of Molecular... Jun 2022Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival,...
Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival, its prognosis remains poor. Established chemotherapeutics include mitomycin C (MMC) and cisplatin (CP), both characterized by severe side effects. GP-2250 is a novel antineoplastic agent, currently under clinical investigation. This in vitro study aims to investigate effects of GP-2250 including combinations with CP and MMC on malignant mesothelioma. JL-1 and MSTO-211H mesothelioma cell lines were treated with increasing doses of GP-2250, CP, MMC and combination therapies of GP-2250 + CP/MMC. Microscopic effects were documented, and a flow-cytometric apoptosis/necrosis assay was performed. Synergistic and antagonistic effects were analyzed by computing the combination index by Chou-Talalay. GP-2250 showed an antiadhesive effect on JL-1 and MSTO-211H spheroids. It had a dose-dependent cytotoxic effect on both monolayer and spheroid cultured cells, inducing apoptosis and necrosis. Combination treatments of GP-2250 with MMC and CP led to significant reductions of the effective doses of CP/MMC. Synergistic and additive effects were observed. GP-2250 showed promising antineoplastic effects on malignant mesothelioma cells in vitro especially in combination with CP/MMC. This forms the basis for further in vivo and clinical investigations in order to broaden treatment options.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Cisplatin; Humans; Mesothelioma; Mesothelioma, Malignant; Mitomycin; Necrosis; Peritoneal Neoplasms
PubMed: 35806313
DOI: 10.3390/ijms23137293 -
Medicine Apr 2016The aim of the study was to assess the effects of bevacizumab in augmenting trabeculectomy for glaucoma. We searched the databases of Cochrane Library, PubMed, Embase,... (Meta-Analysis)
Meta-Analysis Review
The aim of the study was to assess the effects of bevacizumab in augmenting trabeculectomy for glaucoma. We searched the databases of Cochrane Library, PubMed, Embase, CNKI, and VIP. All the databases were retrieved from the time databases established to September, 2015. The keywords we used were as follows: "bevacizumab," "anti-VEGF," "avastin," "trabeculectomy," "glaucoma," and so on. We used a method of the freedom word search and the MeSH search combined, which was recommended by Cochrane Systematic Review Manual 5.1.2. Randomized controlled trails (RCTs) of frequently used bevacizumab in trabeculectomy for glaucoma were included. Study selection, data extraction, quality assessment, and data analysis were performed according to the Cochrane standards. Eight randomized controlled trails involving 212 eyes in the experimental (bevacizumab or bevacizumab + mitomycin C) groups and 214 eyes in the control (mitomycin C or placebo) groups were selected. Compared with placebo, bevacizumab significantly increased the complete success rate [OR = 2.79, 95%CI, (1.47, 5.29), P = 0.002], what else, bevacizumab also significantly decreased the intraocular pressure (IOP) [MD = 3.07, 95% CI, (0.87, 5.27), P = 0.006] at the 6-month after trabeculectomy and the number of antiglaucoma medications [MD = 1.23, 95% CI, (0.66, 1.80), P < 0.0001]. Additionally, it also increased the risk of bleb leak [OR = 5.24, 95% CI, (1.30, 21.10), P = 0.02]. When compared with mitomycin C (MMC), bevacizumab significantly increased the rate of encysted blebs [OR = 4.62, 95% CI, (1.02, 20.91), P = 0.05]. However, there was no significantly difference between the bevacizumab + MMC groups and MMC groups whatever the items were. Bevacizumab was an effective way in trabeculectomy concerning the complete success rate, IOP, and anti-glaucoma medications reduction when compared with placebo; however, it increased the risk of bleb leakage. And it significantly increased the rate of encysted blebs compared with MMC.
Topics: Angiogenesis Inhibitors; Antimetabolites; Bevacizumab; Drug Therapy, Combination; Glaucoma; Humans; Intraocular Pressure; Mitomycin; Randomized Controlled Trials as Topic; Trabeculectomy
PubMed: 27082560
DOI: 10.1097/MD.0000000000003223 -
Scientific Reports Jan 2020Wound healing assay is a simple and cost-effective in vitro assay for assessing therapeutic impacts on cell migration. Its key limitation is the possible confoundment by...
Wound healing assay is a simple and cost-effective in vitro assay for assessing therapeutic impacts on cell migration. Its key limitation is the possible confoundment by other cellular phenotypes, causing misinterpretation of the experimental outcome. In this study, we attempted to address this problem by developing a simple analytical approach for scoring therapeutic influences on both cell migration and cell death, while normalizing the influence of cell growth using Mitomycin C pre-treatment. By carefully mapping the relationship between cell death and wound closure rate, contribution of cell death and cell migration on the observed wound closure delay can be quantitatively separated at all drug dosing. We showed that both intrinsic cell motility difference and extrinsic factors such as cell seeding density can significantly affect final interpretation of therapeutic impacts on cellular phenotypes. Such discrepancy can be rectified by using the actual wound closure time of each treatment condition for the calculation of phenotypic scores. Finally, we demonstrated a screen for strong pharmaceutical inhibitors of cell migration in cholangiocarcinoma cell lines. Our approach enables accurate scoring of both migrastatic and cytotoxic effects, and can be easily implemented for high-throughput drug screening.
Topics: Cell Death; Cell Line; Cell Migration Assays; Cell Migration Inhibition; Cell Movement; Cell Proliferation; Drug Evaluation, Preclinical; Humans; Mitomycin; Wound Healing
PubMed: 31969633
DOI: 10.1038/s41598-020-57806-0 -
Environmental and Molecular Mutagenesis Jul 2010Interstrand cross-links (ICLs) are among the most cytotoxic DNA lesions to cells because they prevent the two DNA strands from separating, thereby precluding replication... (Review)
Review
Interstrand cross-links (ICLs) are among the most cytotoxic DNA lesions to cells because they prevent the two DNA strands from separating, thereby precluding replication and transcription. Even though chemotherapeutic cross-linking agents are well established in clinical use, and numerous repair proteins have been implicated in the initial events of mammalian ICL repair, the precise mechanistic details of these events remain to be elucidated. This review will summarize our current understanding of how ICL repair is initiated with an emphasis on the context (replicating, transcribed or quiescent DNA) in which the ICL is recognized, and how the chemical and physical properties of ICLs influence repair. Although most studies have focused on replication-dependent repair because of the relation to highly replicative tumor cells, replication-independent ICL repair is likely to be important in the circumvention of cross-link cytotoxicity in nondividing, terminally differentiated cells that may be challenged with exogenous or endogenous sources of ICLs. Consequently, the ICL repair pathway that should be considered "dominant" appears to depend on the cell type and the DNA context in which the ICL is encountered. The ability to define and inhibit distinct pathways of ICL repair in different cell cycle phases may help in developing methods that increase cytotoxicity to cancer cells while reducing side-effects in nondividing normal cells. This may also lead to a better understanding of pathways that protect against malignancy and aging.
Topics: Animals; Cisplatin; Codon, Initiator; Cross-Linking Reagents; DNA Repair; Humans; Mitomycin; Transcription, Genetic
PubMed: 20658650
DOI: 10.1002/em.20559 -
Indian Journal of Ophthalmology Dec 2021Photorefractive keratectomy (PRK) is considered a safe approach laser procedure with a clinical significance in correcting myopia results. PRK requires removing the... (Meta-Analysis)
Meta-Analysis Review
Photorefractive keratectomy (PRK) is considered a safe approach laser procedure with a clinical significance in correcting myopia results. PRK requires removing the whole superficial epithelium. The integrity of the epithelial basement membrane and the deposition of abnormal extracellular matrix can put the cornea in a probable situation for corneal haze formation. Mitomycin C (MMC) is applied after excimer laser ablation as a primary modulator for wound healing, limiting corneal haze formation. We aim to summarize the outcomes of MMC application after laser ablation. We searched Scopus, PubMed, Cochrane CENTRAL, and Web of Science till December 2020 using relevant keywords. The data were extracted and pooled as mean difference (MD) or risk ratio (RR) with a 95% confidence interval (CI), using Review Manager software (version 5.4). Our analysis demonstrated a statistically significant result for MMC application over the control group in terms of corneal haze formation postoperatively (RR = 0.29, 95% CI: [0.19, 0.45], P < 0.00001). Regarding corrected distance visual acuity (CDVA), no significant difference was observed between the MMC group and the control group (MD = 0.02; 95% CI: [-0.04, 0.07]; P = 0.56). Regarding the uncorrected distance visual acuity (UDVA), the analysis favored the MMC application with (MD -0.03, 95% CI: [-0.06, -0.00]; P = 0.05). There was no statistically significant increase in complications with MMC. In conclusion, MMC application after PRK is associated with a lower incidence of corneal haze formation with no statistically significant side effects. The long term effect can show improvement regarding UDVA favoring MMC. However, there is no significant effect of MMCs application regarding CDVA, and SE.
Topics: Alkylating Agents; Humans; Lasers, Excimer; Mitomycin; Myopia; Photorefractive Keratectomy
PubMed: 34826969
DOI: 10.4103/ijo.IJO_3768_20