xenograft

异种移植物
  • 文章类型: Journal Article
    目的:评估使用不可吸收的膜和自体骨片的骨移植组合在下颌骨中垂直引导骨再生(GBR)的功效,和高温处理(HTP)异种移植,通过CT扫描和microCT分析。材料和方法:患者在植入前进行垂直隆脊手术。外科手术包括皮瓣抬高和植骨的放置,该植骨包括1:1组合的自体下颌骨后骨碎片,和用d-PTFE膜覆盖的HTP异种移植物颗粒被修整以适合骨缺损的3D形状。这是用钛螺钉和销钉牢固固定的,和一层天然的胶原膜。评估术后并发症和脊测量。从CT扫描获得预骨增强和植入前放置骨参数。通过microCT检查植入过程中收集的活检标本。结果:所有13项研究程序均成功,无任何并发症。结果显示平均垂直和水平骨增加分别为3.35mm和5.15mm。共有33个植入物成功地放置在增强区域,不需要进一步的骨增强。MicroCT分析显示48%的骨头,15%填充材料,和37%的非钙化组织在扩大区域相比,65%的骨,3%填充材料,原骨中32%为非钙化组织.结论:自体骨和HTP异种移植的混合物,覆盖有d-PTFE膜和一层天然胶原膜对垂直GBR有效。
    Purpose: To evaluate the efficacy of vertical guided bone regeneration (GBR) in the mandible utilizing a non-resorbable membrane and a bone graft combination of autogenous bone chips, and high-temperature processed (HTP) xenograft, through CT scans and microCT analysis. Materials and Methods: Patients underwent vertical ridge augmentation procedures prior to implant placement. The surgical procedure included flap elevation and placement of a bone graft comprising a 1:1 combination of autogenous posterior mandible-derived bone chips, and HTP xenograft graft particles covered with a d-PTFE membrane trimmed to suit the 3D shape of the bone defect. This was fastened securely with titanium screws and pins, and a layer of native collagen membrane. Post-operative complications and ridge measurements were assessed. Pre bone augmentation and pre implant placement bone parameters were obtained from CT scans. Biopsy specimens collected during implantation were examined by microCT. Results: All 13 study procedures were successful without any complications. The results revealed average vertical and horizontal bone gains of 3.35 mm and 5.15 mm respectively. A total of 33 implants were successfully placed in the augmented areas, without the need for further bone augmentation. MicroCT analysis revealed 48% bone, 15% filler material, and 37% non-calcified tissue in the augmented region compared to 65% bone, 3% filler material, and 32% non-calcified tissue in the pristine bone. Conclusions: A mixture of autogenous bone and HTP xenograft, covered with a d-PTFE membrane and a layer of native collagen membrane is effective for vertical GBR.
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  • 文章类型: Journal Article
    目的:本研究旨在评估松质骨矿物质颗粒和10%猪胶原蛋白(含胶原蛋白的脱蛋白牛骨矿物质[DBBM-C];(OCS-BCollagen®[StraumannXenoFlex],NIBEC,韩国)以可模制的块状形式,带或不带插座密封,使用自体游离牙龈移植物(FGG)。
    方法:纳入54例患者,随机分为三组:(1)自发愈合(对照组),(2)牙槽嵴保存(ARP)采用DBBM-C(DBBM-C组),和(3)采用用FGG密封的DBBM-C(DBBM-C/FGG组)的ARP。ARP后180天进行骨活检和植入物固定装置放置。锥形束计算机断层扫描,组织学分析,植入物稳定性,并进行了三维体积分析。
    结果:在54例患者中,4人因失去随访和骨整合失败而退出。随访期间牙槽骨的变化没有显着差异。在提取后84天至180天之间,DBBM-C和DBBM-C/FGG组的体积保持在牙槽脊以下3mm(0.72±0.80mm,6.05±6.69%),而对照组的体积减少(-0.37±1.31mm,-2.10%±8.37%)(P=0.026)。DBBM-C/FGG组在牙槽骨下方1mm处表现出较少的水平脊吸收(-9.19±5.09mm,提取前和提取后84天之间的-73.67%±32.53%)(P=0.049)。在所有组中,种植体稳定商保持在70以上。
    结论:在本研究的局限性内,使用DBBM-C的ARP有和没有插座密封有效地保留了牙槽脊的宽度尺寸,牙槽骨吸收无显著差异。然而,插座密封似乎提高了骨移植物的稳定性和骨质量。
    结论:与自发愈合相比,使用DBBM-C治疗ARP似乎有助于容量维持。用FGG密封牙龈可以帮助保持牙槽的宽度。该临床试验在参与者招募和随机化之前未注册。这项研究已在WHOICTRP(https://trialsearch。谁。int/Trial2。aspx?试验ID=KCT0008266)。
    OBJECTIVE: This study sought to evaluate the efficacy of cancellous bovine bone mineral granules and 10% porcine collagen (deproteinized bovine bone mineral with collagen [DBBM-C]; (OCS-B Collagen® [Straumann XenoFlex], NIBEC, Korea) in a mouldable block form, with or without socket seal, using autogenous free gingival graft (FGG).
    METHODS: Fifty-four patients were included and randomly assigned to one of three groups: (1) spontaneous healing (control group), (2) alveolar ridge preservation (ARP) using DBBM-C (DBBM-C group), and (3) ARP employing DBBM-C sealed with FGG (DBBM-C/FGG group). Bone biopsy and implant fixture placement were performed 180 days after ARP. Cone-beam computed tomography, histological analysis, implant stability, and three-dimensional volumetric analysis were conducted.
    RESULTS: Of the 54 patients, 4 dropped out owing to loss of follow-up and osseointegration failure. The changes in alveolar bone during follow-up were not significantly different. Between 84- and 180-day postextraction, the volume of the DBBM-C and DBBM-C/FGG groups was maintained at 3 mm below the alveolar ridge crest (0.72 ± 0.80 mm, 6.05 ± 6.69%), whereas the volume in the control group decreased (-0.37 ± 1.31 mm, -2.10% ± 8.37%) (P = .026). The DBBM-C/FGG group exhibited less horizontal ridge resorption at 1 mm below the alveolar crest (-9.19 ± 5.09 mm, -73.67% ± 32.53%) between preextraction and 84 days postextraction (P = .049). In all groups, the implant stability quotient remained above 70.
    CONCLUSIONS: Within the limitations of this study, both ARP using DBBM-C with and without socket sealing effectively preserved the width dimension of the alveolar ridge, with no significant difference in alveolar bone resorption. However, socket sealing appeared to enhance the stability of the bone graft and bone quality.
    CONCLUSIONS: The use of DBBM-C for ARP seems to aid in volume maintenance as compared with spontaneous healing. Gingival sealing with an FGG can help maintain the width of the alveolar ridge. This clinical trial was not registered prior to participant recruitment and randomization. This study was registered at WHO ICTRP (https://trialsearch.who.int/Trial2.aspx?TrialID=KCT0008266).
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  • 文章类型: Journal Article
    目的:本研究旨在系统地比较使用牛来源的异种移植物和各种合成骨移植材料进行侧向MSFA治疗的患者。
    方法:发布,Scopus,Embase,和Cochrane图书馆在2023年4月之前进行了搜索,并在选定的期刊中进行了手动搜索。报告组织学结果的研究(残余植骨,新形成的骨头,非矿化组织)和临床结果(植入物存活率,ISQ值)包括在内。进行了几项分析,包括荟萃分析,敏感性研究,和Egger的回归测试。
    结果:本系统综述包括16项临床/随机对照试验,其中12人纳入荟萃分析.通过混合HA/TCP在移植窦内新形成的骨的百分比显着高于异种移植物(WMD2.85,95CI[0.72;4.99]),但纯HA(WMD-1.72,95CI[-3.15;-0.29])或TCP(WMD-7.10,95CI[-13.02;-1.17])嫁接的细胞明显低于异种移植物。合成HA产生的残余骨移植物和非矿化组织,TCP,HA/TCP与异种移植组无显着差异。
    结论:外侧MSFA中移植骨替代物的化学性质影响了新形成的骨的数量。与牛来源的HA相比,那些用杂合HA/TCP移植的骨产生的新骨量最高。然而,这种影响对残余骨移植物和非矿化组织不显著.
    OBJECTIVE: This study aimed to systematically compare the patients undergoing lateral MSFA therapies utilizing bovine-originated xenografts versus varied synthetic bone grafting materials.
    METHODS: Pubmed, Scopus, Embase, and Cochrane Library were searched up to April 2023, compensated by a manual search in selected journals. Studies reporting histological outcomes (residual bone graft, newly formed bone, non-mineralized tissue) and clinical outcomes (implant survival, ISQ value) were included. Several analyses were performed, including meta-analysis, sensitivity study, and Egger\'s regression tests.
    RESULTS: Sixteen clinical/randomized control trials were included in this systematic review, among which 12 were enrolled in a meta-analysis. The percentage of newly formed bone within the grafted sinuses by hybrid HA/TCP was significantly higher than those by xenografts (WMD 2.85, 95%CI [0.72; 4.99]), but those grafted by pure HA (WMD -1.72, 95%CI [-3.15; -0.29]) or TCP (WMD -7.10, 95%CI [-13.02; -1.17]) were significantly lower than xenograft counterparts. The residual bone graft and non-mineralized tissue yielded by synthetic HA, TCP, and HA/TCP showed no significant differences with the xenograft group.
    CONCLUSIONS: The chemistry of grafted bone substitutes in lateral MSFA influenced the quantity of newly formed bone. Those grafted with hybrid HA/TCP yielded the highest amount of new bone compared to bovine-originated HA. However, this influence was not significant on residual bone graft and non-mineralized tissue.
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  • 文章类型: Journal Article
    背景:OpenBankart修复和Latarjet稳定是两种用于治疗接触运动员肩关节不稳定的手术方法。这项研究的目的是评估骨块关节镜手术的结果,用异种移植物进行,结合Bankart修复和选择性肩胛骨下增强术(ASA)治疗复发性肩关节前不稳定的接触运动员。
    方法:我们回顾性评估了在2017年1月至2021年12月期间接受关节镜下异种植骨阻滞和Bankart修复并选择性增加肩胛骨下的复发性肩关节前不稳定的接触运动员。排除后向不稳定或多向不稳定的肩关节。复发,并发症,回到运动,和功能分数(Rowe分数,WOSI得分,ASES评分)进行评估。在2年随访时进行CT扫描以评估骨块整合的状态,关节盂表面的移位和修复。
    结果:16名患者被纳入研究,平均年龄为24岁。接受关节镜骨块和ASA治疗的患者均未出现新的脱位发作。在最后一次随访时观察到术前评分增加,特别是ASES,Rowe,WOSI得分从69±7、31±9增加,1235±46分别为96.1±3.2、94±6、119±51。所有运动员都恢复了与手术前相同或接近的运动水平。末次随访时关节盂骨表面从83%增加到116%。
    结论:移植骨块治疗联合Bankart修复和ASA手术已被证明可有效治疗有显著关节盂缺损的接触运动员的不稳定。所有运动员都以与干预前相似的水平恢复了运动活动。
    BACKGROUND: Open Bankart repair and Latarjet stabilization are two of surgical procedures used in the treatment of shoulder instability in contact athletes. The aim of this study is to evaluate the outcomes of bone block arthroscopic procedure, performed with xenograft, in combination with Bankart repair and selective subscapularis augmentation (ASA) for contact athletes with recurrent anterior shoulder instability.
    METHODS: We retrospectively assessed contact athletes who underwent arthroscopic bone block with xenograft and Bankart repair with selective augmentation of subscapularis for recurrent anterior shoulder instability between January 2017 and December 2021. Shoulders with posterior instability or multidirectional instability were excluded. Recurrence, complications, return to sport, and functional scores (Rowe score, WOSI score, ASES score) were assessed. A CT scan at 2-year follow-up was performed to assess the status of Bone block integration, its displacement and restoration of glenoid surface.
    RESULTS: 16 patients were included in the study with a mean age of 24. None of the patients treated with arthroscopic bone block and ASA presented new dislocation episodes. An increase in preoperative scores was observed at the last follow-up, in particular the ASES, Rowe, and WOSI scores increased from 69±7, 31±9 , 1235±46 respectively to 96.1±3.2, 94±6, 119±51. All athletes returned to sporting activity at or near the same level as pre-surgery. The glenoid bone surface increase from 83% to 116% at last follow-up.
    CONCLUSIONS: Bone block treatment with Xenograft combined with Bankart repair and ASA procedures has been shown to be effective in treating instability in contact athletes with significant glenoid deficit. All athletes returned to athletic activity at a level similar to the pre-intervention period.
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  • 文章类型: Journal Article
    近年来,拔牙后保持牙槽脊的重要性明显增加。肺泡脊保存(ARP)是一种常用的技术,各种骨替代材料和生物制剂以不同的组合应用。为此,在ARP后的前瞻性病例系列中,我们研究了组织学评估和随后的引导骨再生(GBR)在延迟种植中的临床必要性,其中包括新型去蛋白牛骨材料(95%)和物种特异性胶原(5%)(C-DBBM).值得注意的是,没有猪胶原蛋白的块状骨替代品是有限的,而且,该材料的组织学数据仍然有限.十个病人,每个计划进行拔牙和希望将来植入,包括在这项研究中。拔牙后,使用C-DBBM的嵌段形式与双折叠牛交联胶原膜(xCM)结合进行ARP。将该膜公开地暴露于口腔并使用十字形缝合线固定。经过130至319天的愈合期,使用静态计算机辅助植入手术(s-CAIS)进行引导环钻以插入植入物。对从先前用ARP处理的区域收获的核进行组织学处理和检查。任何植入都不需要引导骨再生(GBR)。组织学检查显示,在C-DBBM颗粒周围的各个阶段,通过并置膜状成骨作用,形成了松质骨小梁的晶格,以及较大的海绵状或致密小骨,残留最少。临床随访时间为2.5~4.5年,在此期间没有生物或技术并发症发生。在这个前瞻性案例系列的限制下,可以得出结论,使用这种新型C-DBBM与牛xCM结合使用的ARP可能是一种治疗选择,以避免在延迟植入中需要随后的GBR,并有可能获得牛物种特异性生物材料链。
    In recent years, the significance of maintaining the alveolar ridge following tooth extractions has markedly increased. Alveolar ridge preservation (ARP) is a commonly utilized technique and a variety of bone substitute materials and biologics are applied in different combinations. For this purpose, a histological evaluation and the clinical necessity of subsequent guided bone regeneration (GBR) in delayed implantations were investigated in a prospective case series after ARP with a novel deproteinized bovine bone material (95%) in combination with a species-specific collagen (5%) (C-DBBM). Notably, block-form bone substitutes without porcine collagen are limited, and moreover, the availability of histological data on this material remains limited. Ten patients, each scheduled for tooth extraction and desiring future implantation, were included in this study. Following tooth extraction, ARP was performed using a block form of C-DBBM in conjunction with a double-folded bovine cross-linked collagen membrane (xCM). This membrane was openly exposed to the oral cavity and secured using a crisscross suture. After a healing period ranging from 130 to 319 days, guided trephine drilling was performed for implant insertion utilizing static computer-aided implant surgery (s-CAIS). Cores harvested from the area previously treated with ARP were histologically processed and examined. Guided bone regeneration (GBR) was not necessary for any of the implantations. Histological examination revealed the development of a lattice of cancellous bone trabeculae through appositional membranous osteogenesis at various stages surrounding C-DBBM granules as well as larger spongy or compact ossicles with minimal remnants. The clinical follow-up period ranged from 2.5 to 4.5 years, during which no biological or technical complications occurred. Within the limitations of this prospective case series, it can be concluded that ARP using this novel C-DBBM in combination with a bovine xCM could be a treatment option to avoid the need for subsequent GBR in delayed implantations with the opportunity of a bovine species-specific biomaterial chain.
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  • 文章类型: Journal Article
    异种移植骨替代物可以从不同的动物获得,并使用各种方法进行加工。本体内研究评估了在兔颅骨临界尺寸骨缺损中使用三种不同来源的异种移植物后的骨再生。
    在14只新西兰和白色雄性兔子的颅骨中产生了四个8毫米的缺损。四分之三的缺陷充满了牛的异种移植物,骆驼,和鸵鸟的来源。第四个缺损未填充作为对照组。8周后处死7只兔子,12周后处死7只兔子。进一步对解剖的颅骨进行Micro-CT成像和组织学评估。
    8周和12周后,在骆驼组(27.71%和41.92%)和对照组(11.33%和15.96%)中观察到新骨形成的最高和最低百分比,分别。在剩余材料的情况下,鸵鸟组八周后价值最高(53%),而12周后,骆驼组最高(37%)。Micro-CT结果与组织学结果一致。
    尽管所有三种异种移植物都可以是治疗骨缺损的好选择,骆驼来源的异种移植似乎比其他两组更好。异种移植物的起源和加工程序影响其最终特性,应考虑临床使用。
    UNASSIGNED: Xenograft bone substitutes can be obtained from different animals and processed using various methods. The present in vivo study evaluated bone regeneration after using three types of xenografts with different sources in critical-sized bone defects in rabbit calvaria.
    UNASSIGNED: Four 8-mm defects were created in calvaria of 14 New Zealand and white male rabbits. Three out of four defects were filled with xenografts of bovine, camel, and ostrich sources. The fourth defect was left unfilled as the control group. Seven rabbits were sacrificed after eight weeks and seven others after 12 weeks. Micro-CT imaging and histologic evaluation were further performed on dissected calvarias.
    UNASSIGNED: After 8 and 12 weeks, the highest and lowest percentages of new bone formation were observed in the camel (27.71% and 41.92%) and control (11.33% and 15.96%) groups, respectively. In the case of residual material, the ostrich group had the most value after eight weeks (53%), while after 12 weeks, it was highest in the camel group (37%). Micro-CT findings were consistent with histologic results.
    UNASSIGNED: Although all three xenografts can be good choices for treating bone defects, camel-sourced xenograft seemed to be better than the other two groups. The origin and processing procedures of xenografts affected their final characteristics, which should be considered for clinical use.
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  • 文章类型: Journal Article
    背景:与其他干细胞类型相比,间充质来源的干细胞具有良好的增殖能力。牙髓干细胞(DPSC)是从牙齿的牙髓组织获得的多种间充质细胞,并且是大量可用且易于获得的。DPSC使用不同的骨移植支架促进和改善新骨的形成。本研究旨在评估和比较DPSC在同种异体和异种骨移植物上的成骨潜力。
    方法:在实验室中以一式三份的方式使用羟基磷灰石和β-三钙骨移植物和牛骨移植物。DPSC从实验室提取的第三磨牙的牙髓组织中获得。细胞毒性,成骨潜力,并评估了间充质细胞在生物材料上的增殖率差异。
    结果:在MTT比色测定中,在羟基磷灰石/β-三钙骨移植物的情况下观察到较深的紫色染色,表明与牛骨移植物相比,羟基磷灰石/β-三钙骨移植物中的细胞活力增加。与牛骨移植物相比,羟基磷灰石/β-三钙骨移植物显示出更高的成骨潜力,因为在茜素染色中看到了更高的红色染色程度。
    结论:与牛骨支架相比,在羟基磷灰石/β-三钙骨移植物上观察到更高的细胞活力和更高的成骨增殖和分化。
    BACKGROUND: Stem cells of mesenchymal origin have good proliferative capacity when compared to other stem cell types. Dental pulp stem cells (DPSCs) are a variety of mesenchymal cells obtained from the pulpal tissue of teeth and are abundantly available and easy to obtain. DPSCs facilitate and improve the formation of new bone using different bone graft scaffolds. This present study aims to evaluate and compare the osteogenic potential of DPSCs on alloplastic and xenogeneic bone grafts.
    METHODS: Hydroxyapatite and beta-tricalcium bone graft and bovine bone graft were used in a triplicate manner in the laboratory. DPSCs were obtained from the pulpal tissue of extracted third molars in the laboratory. The cytotoxicity, osteogenic potential, and difference in the rate of proliferation of mesenchymal cells on the biomaterials were assessed.
    RESULTS: Darker purple staining was seen in the case of hydroxyapatite/beta-tricalcium bone graft on MTT colorimetric assay stating that there was an increase in cell viability in hydroxyapatite/beta-tricalcium bone graft as compared to the bovine bone graft. Hydroxyapatite/beta-tricalcium bone graft showed more osteogenic potential as compared to the bovine bone graft as a higher degree of red staining was seen in Alizarin staining.
    CONCLUSIONS: Higher cell viability and higher osteogenic proliferation and differentiation were seen on the hydroxyapatite/beta-tricalcium bone graft compared to the bovine bone scaffold.
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  • 文章类型: Journal Article
    患有疾病或治疗会增加其过早性腺功能不全风险的个体可以选择进行生育能力保存。青春期后的人通常可以冷冻保存配子,精子或卵子,使用辅助生殖技术扩大他们的生物家庭。卵巢组织冷冻保存(OTC)和睾丸组织冷冻保存可能是无法使用标准生育力保存技术的个体的一种选择。OTC的发展对许多患者来说至关重要,包括卵巢尚未产卵的青春期前儿童,少产优质卵子的青少年和卵巢不能接受卵巢刺激的成年女性。OTC后恢复生育力和激素产生的唯一选择是通过卵巢组织移植(OTT)。OTC和OTT对于一些患者已经成功。虽然美国生殖医学学会不再认为OTC是实验性的,这个过程远非标准化。需要做大量的研究,尤其是在OTT的时候,提高成功和长寿的卵巢组织功能。本文列出了从手术购买卵巢组织到移植和恢复功能的主要步骤。我们的儿科医院计划不得不决定采购中的哪些选择,processing,冷冻保存和加温将用于我们的临床实验室。简要讨论了研究和分析中的选择和局限性。综述了有关提高OTT有效性和寿命的技术的文献。用配体或药物预处理组织移植物后进行异种移植实验的OTT研究,宿主的治疗,或卵巢组织的包囊被鉴定。治疗的预期效果包括增加血管形成,减少细胞凋亡和指导激活或抑制原始卵泡。该领域的稳健研究必须继续进行严格的分析,以在改善患者的生育能力保护和恢复选择方面取得进展。
    Individuals with a disease or treatment that increases their risk of premature gonadal insufficiency may opt to undergo fertility preservation. Those who are postpubertal can often cryopreserve gametes, sperm, or eggs to expand their biologic family using assisted reproductive technologies. Ovarian tissue cryopreservation (OTC) and testicular tissue cryopreservation may be an option for individuals who are unable to use standard fertility preservation techniques. The development of OTC was critical for many patients, including prepubertal children with ovaries that do not yet produce eggs, adolescents who make few good-quality eggs, and adult women with ovaries who cannot undergo ovarian stimulation. The only option to restore fertility and hormone production after OTC is through ovarian tissue transplantation (OTT). Ovarian tissue cryopreservation and OTT have been successful for some patients. Although OTC is no longer considered experimental by the American Society for Reproductive Medicine, the process is far from standardized. Significant research needs to be done, especially at the point of OTT, to improve the success and longevity of ovarian tissue function. This article lists the main steps from surgical procurement of the ovarian tissue to transplantation and restoration of function. Our pediatric hospital program has had to decide which options in procurement, processing, cryopreservation, and warming will be used in our clinical laboratory. The options and limitations within the research and analyses are briefly discussed. Literature focusing on techniques to improve OTT effectiveness and longevity was reviewed. Ovarian tissue transplantation studies that performed xenograft experiments after pretreatment of the tissue graft by a ligand or drug, treatment of the host, or encapsulation of the ovarian tissue were identified. The intended effects of the treatments include increasing vascularization, reducing apoptosis, and directing activation or suppression of primordial follicles. Robust research in this area must continue with rigorous analyses to make strides in improving fertility preservation and restoration options for patients.
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  • 文章类型: Journal Article
    具有表皮生长因子受体(EGFR)突变的晚期非小细胞肺癌(NSCLC)给新型EGFR抑制剂的发现和开发带来了选择性压力。因此,本研究旨在探讨AraguspongineC(Aragus-C)作为抗癌药物对肺癌的药理作用。评价Aragus-C对A549和H1975细胞的活力的影响。进行了进一步的生化测定以阐述Aragus-C的作用,关于细胞凋亡,细胞周期分析,A549细胞的线粒体膜电位。还进行蛋白质印迹分析以确定EGFR在A549细胞中的表达。建立A549细胞移植瘤小鼠模型,以进一步阐述Aragus-C的药理活性。结果表明,与H1975细胞相比,AragusC对A549细胞显示出明显的抑制活性。已发现Aragus-C引起凋亡的诱导并促进A549细胞在G2/M期的细胞周期停滞。它还显示A549细胞中EGFR的过表达减少。在肿瘤异种移植小鼠模型中,它以剂量依赖的方式显示肿瘤体积显著减小,8mg/kg治疗组报告了最大抑制活性。它还显示了显着的抗炎和抗氧化活性,通过降低TNF-α的水平,IL-1β,IL-6和MDA,同时增加超氧化物歧化酶和谷胱甘肽过氧化物酶。我们已经证明了Aragus-C的有效抗肺癌活性,它可能被认为是NSCLC治疗的潜在治疗选择。
    The advanced non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutations has put a selective pressure on the discovery and development of newer EGFR inhibitors. Therefore, the present study intends to explore the pharmacological effect of Araguspongine C (Aragus-C) as anticancer agent against lung cancer. The effect of Aragus-C was evaluated on the viability of the A549 and H1975 cells. Further biochemical assays were performed to elaborate the effect of Aragus-C, on the apoptosis, cell-cycle analysis, and mitochondrial membrane potential in A549 cells. Western blot analysis was also conducted to determine the expression of EGFR in A549 cells. Tumor xenograft mice model from A549 cells was established to further elaborate the pharmacological activity of Aragus-C. Results suggest that Aragus C showed significant inhibitory activity against A549 cells as compared to H1975 cells. It has been found that Aragus-C causes the induction of apoptosis and promotes cell-cycle arrest at the G2/M phase of A549 cells. It also showed a reduction in the overexpression of EGFR in A549 cells. In tumor xenograft mice model, it showed a significant reduction of tumor volume in a dose-dependent manner, with maximum inhibitory activity was reported by the 8 mg/kg treated group. It also showed significant anti-inflammatory and antioxidant activity by reducing the level of TNF-α, IL-1β, IL-6, and MDA, with a simultaneous increase of superoxide dismutase and glutathione peroxidase. We have demonstrated the potent anti-lung cancer activity of Aragus-C, and it may be considered as a potential therapeutic choice for NSCLC treatment.
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  • 文章类型: Journal Article
    目的:去分化子宫内膜癌(DDEC)以SWItch/蔗糖非发酵(SWI/SNF)复合物失活为特征,是一种高度侵袭性的子宫内膜癌,没有有效的全身治疗选择。其罕见的性质和侵袭性的疾病轨迹对治疗进展提出了重大挑战。为了解决这个障碍,我们专注于开发针对该肿瘤类型的临床前模型,并建立了患者肿瘤来源的DDEC三维(3D)球体模型.
    方法:在DDEC细胞系(SMARCA4灭活的DDEC-1和ARID1A/ARID1B共灭活的DDEC-2)的体外3D球体模型上进行高通量药物再利用筛选。在体外评估已确定的候选药物的剂量-反应关系,然后使用DDEC-1和DDEC-2的异种移植模型进行体内评估。
    结果:在3D模型中的药物筛选确定了包括地高辛和洋地黄毒苷在内的多种强心苷作为DDEC-1和DDEC-2的候选药物。随后的体外剂量反应分析证实了地高辛和洋地黄毒苷的抑制活性,两种药物在DDEC细胞中的IC50均低于非DDEC子宫内膜癌细胞。在体内异种移植模型中,地高辛在临床相关血清浓度下显着抑制DDEC肿瘤的生长。
    结论:使用来自患者肿瘤样本的DDEC的生物学精确临床前模型,我们的研究确定地高辛是抑制DDEC肿瘤生长的有效药物.这些发现为使用地高辛作为SWI/SNF灭活的DDEC的全身治疗提供了令人信服的临床前证据。这也可能适用于其他SWI/SNF灭活的肿瘤类型。
    OBJECTIVE: Dedifferentiated endometrial carcinoma (DDEC) characterized by SWItch/Sucrose Non-Fermentable (SWI/SNF) complex inactivation is a highly aggressive type of endometrial cancer without effective systemic therapy options. Its uncommon nature and aggressive disease trajectory pose significant challenges for therapeutic progress. To address this obstacle, we focused on developing preclinical models tailored to this tumor type and established patient tumor-derived three-dimensional (3D) spheroid models of DDEC.
    METHODS: High-throughput drug repurposing screens were performed on in vitro 3D spheroid models of DDEC cell lines (SMARCA4-inactivated DDEC-1 and ARID1A/ARID1B co-inactivated DDEC-2). The dose-response relationships of the identified candidate drugs were evaluated in vitro, followed by in vivo evaluation using xenograft models of DDEC-1 and DDEC-2.
    RESULTS: Drug screen in 3D models identified multiple cardiac glycosides including digoxin and digitoxin as candidate drugs in both DDEC-1 and DDEC-2. Subsequent in vitro dose-response analyses confirmed the inhibitory activity of digoxin and digitoxin with both drugs showing lower IC50 in DDEC cells compared to non-DDEC endometrial cancer cells. In in vivo xenograft models, digoxin significantly suppressed the growth of DDEC tumors at clinically relevant serum concentrations.
    CONCLUSIONS: Using biologically precise preclinical models of DDEC derived from patient tumor samples, our study identified digoxin as an effective drug in suppressing DDEC tumor growth. These findings provide compelling preclinical evidence for the use of digoxin as systemic therapy for SWI/SNF-inactivated DDEC, which may also be applicable to other SWI/SNF-inactivated tumor types.
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