mitomycin C

丝裂霉素 C
  • 文章类型: Case Reports
    我们对两名患有角膜瘢痕疙瘩的男性患者进行了临床和组织学评估。一名患者因接触沸腾的葵花籽油而有角膜外伤史,而另一例接受了翼状胬肉切除。裂隙灯检查时,角膜病变被确定为单一的,界限分明,珍珠状白色结节,表面光滑。我们使用浅表角膜切除术和丝裂霉素C的联合应用成功地切除了这些结节。破坏了鲍曼的层,基质内不规则排列丰富的胶原纤维。值得注意的是,在手术切除后的6个月内,这两种情况下的病变均未复发。继发性角膜瘢痕疙瘩应被视为角膜结节升高患者的潜在诊断。尤其是有眼表外伤或手术史的时候。
    We conducted clinical and histological evaluations on two male patients who presented with corneal keloid. One patient had a history of corneal trauma due to contact with boiling sunflower oil, while the other had undergone pterygium removal. Upon slit lamp examination, the corneal lesions were identified as single, well-circumscribed, pearly white nodules with a smooth surface. We successfully removed these nodules using a combination of superficial keratectomy and the application of mitomycin C. Light microscopy analysis of the excised nodules revealed hyperplastic epithelium, disrupted Bowman\'s layer, and irregularly arranged abundant collagen fibers within the stroma. Notably, there was no recurrence of the lesions in either case within six months following the surgical excision. Secondary corneal keloids should be considered as a potential diagnosis in patients with elevated corneal nodules, especially when there is a history of ocular surface trauma or surgery.
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  • 文章类型: Case Reports
    范可尼贫血是一种罕见但最普遍的遗传性再生障碍性贫血,主要以常染色体隐性方式传播,除了一个X连接的变体。它来自16个不同互补组的基因突变,这对DNA稳定性至关重要。它的特点是广泛的先天性畸形,进行性全血细胞减少症,血液系统恶性肿瘤和实体瘤的风险增加。与之相关的先天性异常可以影响各种器官系统,包括骨骼系统,患者之间有显著的变异性。这里报道了一个类似的病例,具有典型的FA临床特征。由于不同的表型表现,诊断FA可能具有挑战性。使用丝裂霉素C(MMC)或二环氧丁烷(DEB)的染色体破坏研究是一种独特的细胞标记,有助于诊断。
    Fanconi anemia is a rare but most prevalent form of inherited aplastic anemia, predominantly transmitted in an autosomal recessive manner, except for one X-linked variant. It arises from mutations in the genes across 16 different complementation groups that are crucial for DNA stability. It is marked by a wide range of congenital malformations, progressive pancytopenia, and an increased risk of both hematological malignancies and solid tumors. The congenital abnormalities associated with it can affect various organ systems, including the skeletal system, with significant variability among patients. One similar case has been reported here, which had the typical clinical features of FA. Due to varied phenotypic presentation, diagnosing FA can be challenging. A Chromosomal Breakage Study using mitomycin C (MMC) or diepoxybutane (DEB) is a distinctive cellular marker that aids in the diagnosis.
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  • 文章类型: Journal Article
    背景:增加膀胱内化疗剂渗透度的装置正在成为经典卡介苗(BCG)治疗的替代品。
    目的:比较丝裂霉素C与电动给药装置(MMC-EMDA)和卡介苗在无原位癌(CIS)的中高危非肌层浸润性膀胱癌(NMIBC)患者中的疗效。
    方法:前瞻性非随机研究,其中47例患者接受MMC-EMDA(40mgMMC在50mg蒸馏水中稀释,20mA,30分钟。每周6次,然后每月6次滴注),48例患者接受BCG(50mgOncoCITE®在50ml生理盐水中稀释60分钟。每周滴注6次,然后在第3、6和12个月滴注3次)。主要终点是24个月时的无复发率(RFR)。次要终点是24个月随访时的复发时间和无进展率(PFR)。
    结果:两组患者的基线评估和平均随访时间相似(MMC-EMDA组:26.4个月;BCG组:28.4个月(p=0.44))。24个月时,MMC-EMDA组的RFR为80.9%,BCG组为77.1%(p=0.969)。MMC-EMDA组的平均复发时间为12.5个月,BCG组为14个月(p=0.681)。24个月时,MMC-EMDA组的PFR为97.9%,卡介苗组为93.8%(p=0.419)。
    结论:在没有CIS的高危和中危NMIBC患者中,MMC-EMDA和BCG治疗没有差异。
    BACKGROUND: Devices that increase the penetrance of intravesical chemotherapeutics are emerging as alternatives to classical Bacillus Calmette Guérin (BCG) treatment.
    OBJECTIVE: To compare the efficacy of mitomycin C applied with the electromotive drug delivery device (MMC-EMDA) versus BCG in patients with intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) without carcinoma in situ (CIS).
    METHODS: Prospective non-randomized study in which 47 patients received MMC-EMDA (40 mg of MMC diluted in 50 mg of distilled water at 20 mA for 30 min. Regimen of 6 weekly and then 6 monthly instillations) and 48 patients received BCG (50 mg of OncoCITE® diluted in 50 ml of normal saline for 60 min. Regimen of 6 weekly instillations and then 3 weekly instillations at months 3, 6 and 12). The primary endpoint was the recurrence-free rate (RFR) at 24 months. Secondary endpoints were time to recurrence and progression-free rate (PFR) at 24 months follow-up.
    RESULTS: Baseline patient assessment and mean follow-up time were similar in both groups (MMC-EMDA group: 26.4 months; BCG group: 28.4 months (p = 0.44)). The RFR at 24 months was 80.9% for the MMC-EMDA group and 77.1% for the BCG group (p = 0.969). The mean time to recurrence was 12.5 months in the MMC-EMDA group and 14 months in the BCG group (p = 0.681). At 24 months, PFR was 97.9% in the MMC-EMDA group and 93.8% in the BCG group (p = 0.419).
    CONCLUSIONS: No differences were found between MMC-EMDA and BCG treatments in patients with high-risk and intermediate-risk NMIBC without CIS.
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  • 文章类型: Journal Article
    建立大鼠血浆中丝裂霉素C的液相色谱-串联质谱(LC-MS/MS)测定方法,样品使用固相萃取处理,内标是卡马西平.反相C18柱用于LC-MS/MS研究,并且以0.3mL/min的速率将由在乙腈中的0.1%甲酸和水组成的流动相注入其中。使用前体产物离子对335.3→242.3(丝裂霉素C)和237.1→194.1(卡马西平)的正离子模式进行多反应监测,以定量化合物。血浆中的线性范围为10-4000ng/mL(r2=0.992)。批间和批内精密度分别为<14.3%(LLOQ:14.7%)和13.4%(LLOQ:16.1%),分别。血浆中丝裂霉素C的回收率和基质效应分别为113%和111%,分别。丝裂霉素C在该测定方法的条件下是稳定的。最后,这种方法在对大鼠静脉和口服丝裂霉素C的药代动力学研究中被证明是有效的。
    To develop the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring mitomycin C in rat plasma, samples were processed using solid-phase extraction, with the internal standard being carbamazepine. A reversed phased C18 column was utilized for the LC-MS/MS study, and mobile phases consisting of 0.1 % formic acid in acetonitrile and water were injected into it at a rate of 0.3 mL/min. Multiple reaction monitoring in positive-ion mode with precursor-product ion pairs 335.3 → 242.3 (mitomycin C) and 237.1 → 194.1 (carbamazepine) was employed to quantify the compounds. The linear range in plasma was found to be 10-4000 ng/mL (r2 = 0.992). The inter-batch and intra-batch precision were <14.3 % (LLOQ: 14.7 %) and 13.4 % (LLOQ: 16.1 %), respectively. The recovery and the matrix effect of mitomycin C in plasma were 113 % and 111 %, respectively. Mitomycin C was stable under the conditions of this assay method. In the end, this approach proved effective in a pharmacokinetic investigation with the intravenous and oral administration of mitomycin C to rats.
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  • 文章类型: Case Reports
    报告3例孤立性角膜上皮内瘤变(CIN)的临床特征和治疗结果。
    本病例系列介绍了3例孤立的CIN。收集的数据包括,表现出包括视力在内的体征和症状,眼前段检查,治疗后就诊失败时的内科和外科结果以及体征和症状。
    病例1是一名45岁的男性,患有孤立的灰色变形虫角膜病变,该病变通过酒精辅助上皮切除术切除,他还接受了6个周期的局部用丝裂霉素C(MMC)0.02%和1次注射干扰素α-2b,在10年随访期间没有复发.病例2为78岁男性,因可疑白色角膜病变被完全切除,患者还接受了6次结膜下注射干扰素α-2b.然而,病变在治疗后2.5年复发。病例3是一名63岁的男性患者,其表现为使用酒精辅助上皮切除术切除的孤立性角膜病变。在6个月的最后一次随访时,患者接受了4个周期的局部用5-氟尿嘧啶治疗,没有复发.
    孤立的角膜上皮内瘤变(CIN)是一种罕见的实体,在文献中报道的病例很少。在这个系列中,我们报告了孤立性CI的联合手术和药物治疗的长期和短期管理结果。
    UNASSIGNED: To report clinical features and treatment outcome of three cases with isolated corneal intraepithelial neoplasia (CIN).
    UNASSIGNED: This case series presents 3 patients with isolated CIN. Data collected included, presenting signs and symptoms including vision, anterior segment examination, medical and surgical outcomes and signs and symptoms at lost post-treatment visit.
    UNASSIGNED: Case 1 was a 45-year-old male who presented with an isolated grayish amoeboid corneal lesion which was excised with alcohol assisted epitheliectomy, he also received 6 cycles of topical mitomycin C (MMC) 0.02% and one injection of interferon alfa-2b with no recurrence during the 10-year follow-up period. Case 2 was 78-year-old male referred for a suspicious white corneal lesion which was completely excised, the patient also received 6 subconjunctival injections of interferon alpha-2b. However, the lesion recurred at 2.5-years post-treatment. Case 3 was a 63-year-old male patient who presented with an isolated corneal lesion that was excised using alcohol-assisted epitheliectomy, patient received four cycles of topical 5-fluorouracil with no recurrence at last follow-up visit at 6 months.
    UNASSIGNED: Isolated corneal intraepithelial neoplasia (CIN) is a rare entity with few reported cases in the literature. In this case series, we report long and short-term management outcomes of combined surgical and medical therapy for isolated CIN.
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  • 文章类型: Journal Article
    非肌肉浸润性膀胱癌是男性和女性常见的肿瘤。在对标准治疗剂有抗性的情况下,吉西他滨可用作非标记性膀胱滴注疗法。为了减少潜在的副作用,不断努力优化药物的治疗潜力,从而降低了有效剂量,从而降低了药物的药理负担。我们最近证明,通过暴露于无毒剂量的蓝光(453nm),可以显着提高丝裂霉素C对膀胱癌细胞系的治疗效果。在本研究中,我们研究了额外使用波长特异性光敏剂核黄素是否可以进一步增强蓝光的治疗支持作用.我们发现,在核黄素存在下,无毒剂量的蓝光显着增强了吉西他滨诱导的膀胱癌细胞系(BFTC-905,SW-1710,RT-112)的细胞毒性。与线粒体ATP合成水平降低和脂质过氧化增加相关的细胞毒性增强很可能是氧化应激增加的结果。由于这些属性,蓝光结合核黄素可以代表一种有效的治疗选择,副作用少,增加膀胱癌局部治疗的成功率,由此使用的化疗剂的剂量和因此的化学负荷可以显著降低,具有相似或改善的治疗成功。
    Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise the therapeutic potential of drugs, thereby reducing the effective dose and consequently the pharmacological burden of the medication. We recently demonstrated that it is possible to significantly increase the therapeutic efficacy of mitomycin C against a bladder carcinoma cell line by exposure to non-toxic doses of blue light (453 nm). In the present study, we investigated whether the therapeutically supportive effect of blue light can be further enhanced by the additional use of the wavelength-specific photosensitiser riboflavin. We found that the gemcitabine-induced cytotoxicity of bladder cancer cell lines (BFTC-905, SW-1710, RT-112) was significantly enhanced by non-toxic doses of blue light in the presence of riboflavin. Enhanced cytotoxicity correlated with decreased levels of mitochondrial ATP synthesis and increased lipid peroxidation was most likely the result of increased oxidative stress. Due to these properties, blue light in combination with riboflavin could represent an effective therapy option with few side effects and increase the success of local treatment of bladder cancer, whereby the dose of the chemotherapeutic agent used and thus the chemical load could be significantly reduced with similar or improved therapeutic success.
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  • 文章类型: Journal Article
    目的:比较丝裂霉素C和曲安奈德浸渍的生物可降解鼻腔填塞(TABP)辅助应用于鼻内镜下鼻腔泪囊吻合术(DCR)的成功率和并发症。并评价术中结合丝裂霉素C和TABP用于内镜下DCR的疗效。
    方法:对148例因获得性鼻泪管阻塞而接受内镜下DCR治疗的198只眼进行回顾性分析。将患者随机分为三组:A组包括术中不使用丝裂霉素C但使用TABP的患者,B组包括不使用曲安奈德但术中使用丝裂霉素C和生理盐水灌注鼻腔填塞的患者,C组包括术中接受丝裂霉素C和TABP治疗的患者。
    结果:结果显示A组(86.8%)和B组(89.2%;P=0.377)之间的总体成功率没有显着差异。然而,C组(97.5%)的总体成功率明显高于A组和B组,C组(5%)的肉芽肿发生率明显低于A组(20.8%)和B组(15.2%,P=0.009)。其他并发症,比如地壳,synechiae,和翻修手术,三组间无显著差异。
    结论:术中联合应用丝裂霉素C和TABP可有效预防肉芽肿,提高手术成功率。此外,单独使用丝裂霉素C或TABP之间没有统计学上的显着差异。
    OBJECTIVE: To compare the success rate and complications of adjuvant use of mitomycin C and triamcinolone-impregnated biodegradable nasal packing (TABP) in endoscopic dacryocystorhinostomy (DCR). And to evaluate the efficacy of combining intraoperative mitomycin C and TABP for endoscopic DCR.
    METHODS: A total of 198 eyes of 148 patients who underwent endoscopic DCR for acquired nasolacrimal duct obstruction were retrospectively analysed. The patients were randomly divided into three groups: Group A included patients treated without intraoperative mitomycin C but with TABP, Group B included patients treated without triamcinolone but with intraoperative mitomycin C and normal saline-impregnated nasal packing, and Group C included patients treated with intraoperative mitomycin C and TABP.
    RESULTS: The results revealed no significant difference in the overall success rates between Groups A (86.8%) and B (89.2%; P=0.377). However, Group C (97.5%) showed a significantly higher overall success rate than Groups A and B. The incidence of granulomas was significantly lower in group C (5%) than in Groups A (20.8%) and B (15.2%; P=0.009). Other complications, such as crust, synechiae, and revision surgery, did not differ significantly among the three groups.
    CONCLUSIONS: The combination of intraoperative mitomycin C and TABP effectively prevents granulomas and enhances surgical success rate. Additionally, there is no statistically significant difference observed between the use of mitomycin C or TABP alone.
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  • 文章类型: Journal Article
    目的:研究在兔凝胶支架植入模型中,有和没有术中缓释丝裂霉素C(MMCSR)的凝胶支架植入。并检查房水流出(AHO)植入后。方法:纳入4组家兔。第1组未经处理(对照)。第2、3和4组接受无MMC的凝胶支架,用MMC溶液(结膜下注射),和MMCSR(结膜下注射),分别。眼压(IOP)和AHO通过眼压测量和吲哚菁绿血管造影评估,分别。主要疗效指标是眼压从基线的变化。结果:凝胶支架植入术后,第2、3和4组维持IOP降低≥20%(反应),中位持续时间为1周,6.5周,30周,分别。血管造影显示正常的房水引流(第1组)始于周围的小梁丛,并向后延续到巩膜流出血管。植入后,引流优先发生并直接进入结膜下泡。结论:用MMCSR进行凝胶支架植入最有效地实现了持续的,兔模型的长期IOP降低,与有或没有MMC溶液的植入相比。Bleb的存在和植入后的房水血管造影结果表明AHO重定向到结膜下脉管系统和假定的淋巴管,提示在该模型中有效的青光眼滤过可以降低IOP。这种兔模型和房水血管造影术可能有助于加深对微创青光眼手术的作用机制的理解,并最终转化为改善青光眼患者的手术设备和程序。
    Purpose: To investigate gel stent implantation with and without intraoperative sustained-release mitomycin C (MMC SR) in a rabbit model for gel stent implantation, and to examine aqueous humor outflow (AHO) postimplantation. Methods: Four groups of rabbits were included. Group 1 was untreated (control). Groups 2, 3, and 4 received the gel stent without MMC, with MMC solution (subconjunctival injection), and with MMC SR (subconjunctival injection), respectively. Intraocular pressure (IOP) and AHO were assessed via tonometry and indocyanine green-based angiography, respectively. The main efficacy measure was change in IOP from baseline. Results: Following gel stent implantation, Groups 2, 3, and 4 maintained ≥20% IOP reduction (response) for a median duration of 1 week, 6.5 weeks, and 30 weeks, respectively. Angiography showed normal aqueous humor drainage (Group 1) beginning at the perilimbal trabecular plexus and continuing posteriorly to episcleral outflow vessels. Following implantation, drainage occurred preferentially and directly into the subconjunctival bleb. Conclusions: Gel stent implantation with MMC SR was most effective in achieving sustained, long-term IOP reduction in the rabbit model, compared with implantation with or without MMC solution. Bleb presence and the postimplantation aqueous angiography results indicated redirection of the AHO to the subconjunctival vasculature and presumed lymphatics, suggesting efficient glaucoma filtration to lower IOP in this model. This rabbit model and aqueous angiography may help refine understanding of the mechanism of action of minimally invasive glaucoma surgeries and ultimately translate to improved surgical devices and procedures for patients with glaucoma.
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  • 文章类型: Journal Article
    丝裂霉素C(MC)是一种抗癌药物,通过在相对的DNA链之间形成链间交联(ICL)起作用。MC模拟,10-脱氨甲酰基丝裂霉素C(DMC),与MC不同,对TP53突变的癌细胞具有更强的细胞毒性作用。我们先前证明了MC/DMC可以以TP53非依赖性模式激活MCF-7(TP53有效)和K562(TP53缺陷型)细胞中的p21WAF1/CIP1。我们还发现,MC/DMC以TP53依赖性方式调节AKT激活,并且AKT失活与MC/DMC治疗后p21WAF1/CIP1的激活无关。RAS蛋白是导致控制细胞增殖和细胞死亡的p21WAF1/CIP1活化的上游介导的信号传导中的已知参与者。因此,这促使我们研究两种药物对MCF-7和K562癌细胞中RAS蛋白表达和MAPK/ERK信号通路调节的影响。为了实现这个目标,我们进行了与生物信息学/互补磷蛋白阵列偶联的无标记蛋白质组学比较分析,以及关键信号分子的westernblot验证.在MCF-7细胞中,MAPK/ERK途径在MC/DMC处理后表现出整体下调,但在TP53突变体K562细胞中,仅DMC表现出相同途径的轻度下调。此外,用含有由MC或DMC形成的链间交联(ICL)的寡核苷酸处理MCF-7和K562细胞系表明,两种ICL对突变体TP53K562细胞中RAS蛋白表达的下调具有更强的作用。我们讨论了MAPK/ERK途径的这种调节与细胞TP53状态有关的含义。
    Mitomycin C (MC) is an anti-cancer drug which functions by forming interstrand crosslinks (ICLs) between opposing DNA strands. MC analog, 10-decarbamoyl mitomycin C (DMC), unlike MC, has stronger cytotoxic effects on cancer cells with TP53 mutation. We previously demonstrated that MC/DMC could activate p21WAF1/CIP1 in MCF-7 (TP53-proficient) and K562 (TP53 deficient) cells in a TP53-independent mode. We also found that MC/DMC regulate AKT activation in a TP53-dependent manner and that AKT deactivation is not associated with the activation of p21WAF1/CIP1 in response to MC/DMC treatment. RAS proteins are known players in the upstream mediated signaling of p21WAF1/CIP1 activation that leads to control of cell proliferation and cell death. Thus, this prompted us to investigate the effect of both drugs on the expression of RAS proteins and regulation of the MAPK/ERK signaling pathways in MCF-7 and K562 cancer cells. To accomplish this goal, we performed comparative label free proteomics profiling coupled to bioinformatics/complementary phosphoprotein arrays and Western blot validations of key signaling molecules. The MAPK/ERK pathway exhibited an overall downregulation upon MC/DMC treatment in MCF-7 cells but only DMC exhibited a mild downregulation of that same pathway in TP53 mutant K562 cells. Furthermore, treatment of MCF-7 and K562 cell lines with oligonucleotides containing the interstrand crosslinks (ICLs) formed by MC or DMC shows that both ICLs had a stronger effect on the downregulation of RAS protein expression in mutant TP53 K562 cells. We discuss the implication of this regulation of the MAPK/ERK pathway in relation to cellular TP53 status.
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  • 文章类型: Journal Article
    背景:目的是评估辅助丝裂霉素c(MMC)的原发性小梁切除术治疗青光眼的长期疗效和疗效。方法:我们检查了2008年至2009年在弗莱堡大学眼科医院接受小梁切除术的286只眼的病历,德国。收集术前、随访资料,包括眼内压(IOP)测量,手术青光眼干预,并开了青光眼药物。第一个成功标准定义为患者不使用降压药物的IOP≤15mmHg。第二个标准被定义为没有手术翻修,第三个标准是不进行小梁切除术后早期修正的降低IOP手术。统计分析包括Cox回归和Kaplan-Meier生存估计。结果:平均随访时间为1841天(5年)。术前平均IOP为26.1mmHg。在平均随访时评估成功标准,第一个标准的成功率仅为25%,而第二个和第三个成功标准的成功率均为80%。结论:研究结果表明,辅助MMC的小梁切除术可能是永久性降低IOP的有效方法。然而,可能仍需要进行手术修正和/或进一步的青光眼手术.与以前的研究相比,长期成功率较低,这可以解释为我们研究中更严格的成功标准。
    Background: The aim was to evaluate the long-term outcome and efficacy of primary trabeculectomy with adjunctive mitomycin c (MMC) for treating glaucoma. Methods: We examined the medical records of 286 eyes that underwent trabeculectomy between 2008 and 2009 at the University Eye Hospital in Freiburg, Germany. Preoperative and follow-up data were collected, including intraocular pressure (IOP) measurements, surgical glaucoma interventions, and prescribed glaucoma medication. The first success criterion was defined as IOP ≤ 15 mmHg with no use of pressure-lowering medication by the patient, the second criterion was defined as the absence of surgical revision, and the third criterion as no further IOP-lowering surgery excluding early revisions following trabeculectomy. Statistical analyses comprised Cox regression and Kaplan-Meier survival estimations. Results: The mean follow-up duration was 1841 days (5 years). The mean preoperative IOP was 26.1 mmHg. Evaluating the success criteria at the time of average follow-up yielded a success rate of only 25% for the first criterion but 80% for both the second and third success criteria. Conclusions: The findings suggest that trabeculectomy with adjunctive MMC can be an effective procedure for permanently lowering IOP. However, surgical revisions and/or further glaucoma surgeries might still be needed. The long-term success rate is lower in comparison to previous research, which may be explained by the stricter success criteria in our study.
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