lung tumor

肺肿瘤
  • 文章类型: Journal Article
    肺硬化性肺细胞瘤(PSP)是一种罕见的,良性肿瘤。鉴于支气管镜诊断的挑战,手术是在疾病的早期阶段进行的。因此,对PSP的生长模式知之甚少。尽管进行了支气管镜检查,但仍未诊断为PSP,在首次在计算机断层扫描(CT)上发现异常8年后,导致肺切除术。本报告比较了CT和病理结果的长期随访,并讨论了使用支气管镜钳活检进行诊断以帮助将来进行PSP诊断和治疗计划的困难。
    Pulmonary sclerosing pneumocytoma (PSP) is a rare, benign tumor. Given the challenges of a bronchoscopic diagnosis, surgery is performed during the early stages of the disease. Therefore, little is known about the growth pattern of PSP. This case of PSP was not diagnosed despite bronchoscopy, resulting in lung resection eight years after the anomaly was first identified on computed tomography (CT). This report compares the long-term follow-up of CT and pathological findings and discusses the difficulty in making a diagnosis using a bronchoscopic forceps biopsy to aid in future PSP diagnoses and treatment planning.
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  • 文章类型: Journal Article
    用于癌症免疫治疗的4-1BB激动剂在临床试验中显示出良好的初步疗效,但进入临床的几种第一代4-1BB激动性抗体由于安全性问题而失败。硒纳米颗粒(SeNPs)表现出抗炎,抗肿瘤,抗氧化剂,和免疫调节特性。此外,它们已被证明具有解毒作用并防止氧化性肝损伤。在这项研究中,我们使用抗4-1BB抗体与SeNPs组合在体外和体内实验中评估抗肺癌作用,并通过病理分析探索潜在的机制,定量PCR,和酶联免疫测定。我们发现5μmol·L-1抗4-1BB抗体联合1μmol·L-1SeNPs增加IFN-γ的表达并促进外周血单个核细胞对Lewis肺癌细胞的杀伤作用。致死率高达56.88%。荷瘤小鼠实验表明,用3.5mg/kg抗4-1BB抗体联合0.25mg/kgSeNPs治疗后,抑瘤率为58.61%,肝功能指标恢复正常。当联合治疗与单独的抗体治疗相比,免疫相关因子检测显示脾脏中FOXP3、IL-2、IL-12和TNF-α的表达下调,而IFN-γ在脾脏中的表达,血清,肿瘤上调,伴随着肿瘤组织中Fas配体表达的增加。基于这些发现,结论抗4-1BB抗体联合SeNPs可以减轻调节性T细胞的免疫抑制,促进免疫细胞增殖和转移,协同杀伤肿瘤细胞。这种组合还减少了对正常组织的炎症损伤并减缓了脾免疫应答的过度刺激。
    4-1BB agonists for cancer immunotherapy have shown good preliminary efficacy in clinical trials, but several of the first-generation 4-1BB agonistic antibodies entering the clinic have failed due to safety issues. Selenium nanoparticles (SeNPs) exhibit anti-inflammatory, anti-tumor, antioxidant, and immune-modulating properties. In addition, they have been shown to have detoxifying effects and prevent oxidative liver damage. In this study, we used an anti-4-1BB antibody in combination with SeNPs to evaluate the anti-lung cancer effects in in vitro and in vivo experiments and explore the underlying mechanisms by pathological analyses, quantitative PCR, and enzyme-linked immunoassay. We found that 5 μmol·L-1 anti-4-1BB antibody combined with 1 μmol·L-1 SeNPs increased the expression of IFN-γ and promoted the killing effects of peripheral blood mononuclear cells on Lewis lung carcinoma cells, with a lethality rate up to 56.88 %. Experiments in tumor-bearing mice showed that the tumor inhibition rate was 58.61 % after treatment with 3.5 mg/kg anti-4-1BB antibody combined with 0.25 mg/kg SeNPs, and the liver function index returned to normal. When the combined treatment was compared with the antibody treatment alone, detection of immune relevant factors demonstrated that the expression of FOXP3, IL-2, IL-12, and TNF-α in the spleen was downregulated, whereas the expression of IFN-γ in the spleen, serum, and tumor was upregulated, accompanied by increased Fas ligand expression in the tumor tissues. Based on these findings, we get the conclusion that anti-4-1BB antibody combined with SeNPs may alleviate the immunosuppression of regulatory T cells, promote the immune cell proliferation and metastasis to synergistically kill tumor cells. This combination also reduces the inflammatory damage to normal tissues and slows overstimulation of the splenic immune response.
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  • 文章类型: Journal Article
    在过去几十年的科学文献中发表的许多关于人类和实验动物的研究已经评估了滑石的潜在致癌性。许多研究报告说,滑石粉暴露与任何类型的癌症之间没有关联。为了充分了解有关滑石粉诱发人类癌症的潜力的科学现状,我们对现有的实验动物和机制证据进行了全面和系统的回顾(同时对伴随分析中的流行病学证据进行了系统回顾),以评估滑石粉是否对人类具有致癌性.我们考虑了研究质量及其对结果解释的影响,并评估了所有类型的癌症和所有暴露途径。我们还评估了滑石粉在体内迁移到潜在肿瘤部位的可能性的证据。我们确定了7项实验动物致癌性研究和11项滑石粉机理研究,以进行系统回顾。我们发现,一些滑石粉的实验性动物致癌性研究具有局限性,使其无法检测肿瘤发病率增加的敏感性。无论如何,这些研究涵盖了多种暴露途径,物种,和暴露持续时间,并且没有表明滑石粉在实验动物中是致癌物,除了在极高暴露条件下可能导致肺颗粒超负荷的大鼠中,高暴露于难溶颗粒的非特异性效应,而不是来自滑石的任何致癌特性。导致肺部肿瘤形成的肺颗粒超负荷仅在大鼠中观察到,而在任何其他物种中均未观察到,包括人类。机理研究表明,滑石没有遗传毒性或诱变性,但可以诱导一些可能是致癌途径的事件,主要是在高暴露或体外研究中,体内暴露的相关性不明确,但是这些影响在研究和细胞类型之间并不一致。这项对实验动物致癌性和滑石粉机理证据的系统评价表明,在人类中不会出现滑石粉暴露与癌症之间的关联。滑石致癌性在除大鼠以外的任何物种中都是不可能的,只有当暴露条件高到足以诱发肺颗粒超负荷时,这与人类暴露无关。
    The potential carcinogenicity of talc has been evaluated in many studies in humans and experimental animals published in the scientific literature over the last several decades, with a number of these studies reporting no associations between talc exposure and any type of cancer. In order to fully understand the current state of the science regarding the potential for talc to induce human cancers, we conducted a comprehensive and systematic review of the available experimental animal and mechanistic evidence (in conjunction with a systematic review of the epidemiology evidence in a companion analysis) to evaluate whether it supports talc as being carcinogenic to humans. We considered study quality and its impact on the interpretation of results and evaluated all types of cancer and all exposure routes. We also evaluated the evidence on the potential for talc to migrate in the body to potential tumor sites. We identified seven experimental animal carcinogenicity studies and 11 mechanistic studies of talc to systematically review. We found that several of the experimental animal carcinogenicity studies of talc have limitations that preclude their sensitivity to detect increases in tumor incidence. Regardless, the studies cover multiple exposure routes, species, and exposure durations, and none indicate that talc is a carcinogen in experimental animals except in rats under conditions of extremely high exposure that likely resulted in lung particle overload, a nonspecific effect of high exposures to poorly soluble particles, and not from any carcinogenic properties of talc. Lung particle overload leading to lung tumor formation has only been observed in rats and not in any other species, including humans. The mechanistic studies indicate that talc is not genotoxic or mutagenic, but can induce some effects that could be events on a possible pathway to carcinogenicity, mainly at high exposures or in in vitro studies with exposures of unclear relevance in vivo, but these effects are not consistent across studies and cell types. This systematic review of the experimental animal carcinogenicity and mechanistic evidence for talc indicates that an association between talc exposure and cancer is not expected in humans. Talc carcinogenicity is not plausible in any species except rats, and only when the exposure conditions are high enough to induce lung particle overload, which is not relevant to human exposures.
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  • 文章类型: Journal Article
    目的:经皮肺肿瘤消融大多在计算机断层扫描(CT)室进行,局部麻醉和清醒镇静。然而,在此期间保持屏气阶段可能具有挑战性,影响图像质量和增加并发症。随着混合手术室(HORs)的出现,该程序可以在全身麻醉下进行气管导管(ETGA)插管,并进行肺分离,确保在一个单一的阶段设置精确的成像。肺分离提供一个肺的手术暴露,同时确保与另一个充分的气体交换。这项研究评估了在配备锥形束CT和激光引导的HOR中进行的肿瘤消融。
    方法:这项回顾性研究包括在2020年7月至2023年5月期间在全麻下在HOR中使用ETGA进行肺肿瘤消融的患者。麻醉方面的考虑,围手术期管理,术后随访进行评估。
    结果:65例患者(78个肿瘤)使用两种类型的肺通气方法进行了消融,包括带有阻滞剂的单腔管(SLT/BL)(n=15)和双腔管(DLT)(n=50)。大多数患者在动态CT和针刺的呼吸暂停阶段经历了去饱和。术中DLT组的平均SpO2值显着低于SLT/BL组(81.1%对88.7%,P=0.033)。五、三,两名患者出现气胸,皮下气肿,和胸腔积液,分别。
    结论:全身麻醉下气管插管经皮消融并在HOR中进行肺分离是可行且安全的。该设置将并发症风险降至最低,并在患者安全和成功手术之间保持平衡。
    OBJECTIVE: Percutaneous lung tumor ablations are mostly performed in computed tomography (CT) rooms under local anesthesia with conscious sedation. However, maintaining the breath-hold phase during this can be challenging, affecting image quality and increasing complications. With the advent of hybrid operating rooms (HORs), this procedure can be performed with endotracheal tube (ETGA) intubation under general anesthesia with lung separation, ensuring precise imaging in a single-stage setting. Lung separation provides surgical exposure of one lung while ensuring ample gas exchange with the other. This study evaluated tumor ablations performed in an HOR equipped with cone beam CT and laser guidance.
    METHODS: This retrospective study included patients who underwent lung tumor ablation under general anesthesia with an ETGA in an HOR between July 2020 and May 2023. Anesthesia considerations, perioperative management, and postoperative follow-ups were evaluated.
    RESULTS: 65 patients (78 tumors) underwent ablation using two types of lung ventilation methods including a single-lumen tube with a blocker (SLT/BL) (n = 15) and double-lumen tube (DLT) (n = 50). Most patients experienced desaturation during the apnea phase of dynamic CT and needling. The average SpO2 value was significantly lower in the DLT group than in the SLT/BL group during the procedure (81.1% versus 88.7%, P = 0.033). Five, three, and two patients developed pneumothorax, subcutaneous emphysema, and pleural effusion, respectively.
    CONCLUSIONS: Percutaneous ablation under general anesthesia with endotracheal intubation and lung separation performed in HORs was feasible and safe. The setup minimized complication risks and maintained a balance between patient safety and successful procedures.
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  • 文章类型: Journal Article
    I,作者,对2023年5月获得第45届Juntendo医学院校友会学术鼓励奖表示感谢。在Juntendo大学完成医学院和外科培训后,我通过攻读博士学位开始了一项新的挑战。在基础临床研究中,专注于胃癌,在日本,癌症相关死亡的第三大原因。与各种专家合作,我在2014年获得了癌症研究博士学位。随后,我在美国寻求进一步的研究机会,在那里,我承担了多个项目,重点关注癌症和产妇压力。我想介绍几项研究,ERC/间皮素,脂肪酸合成酶,和这份手稿中的母体压力。在2019年回到准腾多大学静冈医院的临床实践时,我对各种临床问题产生了兴趣,并决定通过实验解决这些问题。与静冈医学灾难研究中心的几位研究人员合作,我们正在进行的研究旨在回答几个临床问题.此外,我渴望在未来指导初级员工,并感谢JuntendoUniversity提供的宝贵联系和机会。
    I, the author, expressed gratitude for receiving the 45th Juntendo Medical School Alumni Association Academic Encouragement Award in May 2023. After completing medical school and surgical training at Juntendo University, I embarked on a new challenge by pursuing a Ph.D. in basic clinical research, with a focus on gastric cancer, the third leading cause of cancer related death in Japan. Collaborating with various experts, I obtained a Ph.D. in cancer research studies in 2014. Subsequently, I pursued further research opportunities in the United States, where I undertook multiple projects focusing on cancer and maternal stress. I would like to present several studies, ERC/mesothelin, fatty acid synthase, and maternal stress in this manuscript. On returning to clinical practice at Juntendo University Shizuoka Hospital in 2019, I developed an interest in various clinical issues and decided to address these through experiments. In collaborating with several researchers at the Shizuoka Medical Research Center for Disasters, our ongoing research aims to answer several clinical questions. Furthermore, I aspire to guide junior staff in the future and am grateful for the invaluable connections and opportunities provided by Juntendo University.
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  • 文章类型: Journal Article
    我们已经使用基于Anzai激光的门控设备与视觉引导结合Elekta线性加速器,在腹部压迫下实施了门控立体定向放射治疗。为了确保准确性,我们通过关联来自激光传感器的呼吸曲线和来自借助呼吸曲线重建的4D计算机断层扫描(CT)图像的肿瘤位置,为每位患者配置了门控窗口.这使我们能够定义一个患者特定的门控窗口,以保持肿瘤位移在5毫米以下,从结束呼气,假设肿瘤轨迹的可重复性和基于激光的体表测量。结果总结如下:1)通过采集由20个相位CT集和呼吸曲线组成的4DCT,获得了患者特定的门控窗口内部目标体积(ITV),该目标体积相对于呼气末具有预定的最大肿瘤位移。来自Anzai系统。2)通过基于预定的相对于呼气末的最大肿瘤位移在呼吸曲线上设置两个不同的阈值来管理呼吸滞后。3)腹部压缩增加门控窗口宽度,从而可能导致更快的门控光束传输。4)滑窗门控调强放疗(IMRT)的伽马指数通过率优于门控体积调强治疗(VMAT)。5)帧内门控锥形束计算机断层扫描(CBCT)表明,在立体定向门控滑动窗口IMRT期间,肿瘤似乎仍保留在门控窗口ITV内。总之,我们在临床上成功实施了门控立体定向放射治疗,并取得了良好的临床验证结果。需要评估更多的案例以提高有效性。
    We have clinically implemented gated stereotactic body radiotherapy under abdominal compression using an Anzai laser-based gating device with visual guidance in combination with an Elekta linear accelerator. To ensure accuracy, we configured the gating window for each patient by correlating the respiratory curve from the laser sensor and the tumor positions from the 4D computed tomography (CT) images reconstructed with the aid of the respiratory curve. This allowed us to define a patient-specific gating window to keep the tumor displacement below 5 mm from the end-expiration, assuming the reproducibility of the tumor trajectories and the laser-based body surface measurements. Results are summarized as follows: 1) A patient-specific gating window internal target volume (ITV) with a prespecified maximum tumor displacement relative to the end-expiration was obtained by acquiring a 4D CT consisting of 20 phase CT sets and a respiratory curve from the Anzai system. 2) Respiratory hysteresis was managed by setting two different thresholds on the respiratory curve based on the predetermined maximum tumor displacement relative to end-expiration. 3) Abdominal compression increased gating window width, thereby presumably leading to faster gated-beam delivery. 4) Gamma index pass rates in sliding-window gated intensity-modulated radiotherapy (IMRT) were superior to those in gated volumetric modulated arc therapy (VMAT). 5) Intrafraction gated cone-beam computed tomography (CBCT) demonstrated that the tumor appeared to remain within the gating window ITV during the stereotactic gated sliding-window IMRT. In conclusion, we have successfully implemented gated stereotactic body radiotherapy at our clinic and achieved a favorable clinical validation result. More cases need to be evaluated to increase the validity.
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  • 文章类型: Journal Article
    由于费用高昂,某些患者的4D-CT数据可能仅包括五个呼吸阶段(0%,20%,40%,60%,和80%)。由于其余五个呼吸阶段缺乏肺部肿瘤信息,因此这种限制可能会影响后续的放射治疗计划(10%,30%,50%,70%,90%)。本研究旨在开发一种插值方法,该方法可以使用可用的5相4D-CT数据自动得出五个省略相的肿瘤边界轮廓。动态模式分解(DMD)方法是一种数据驱动且无模型的技术,可以从高维数据中提取动态信息。它能够仅使用有限数量的时间快照来重建长期动态模式。由呼吸运动引起的可变形肺肿瘤的准周期性运动使其适合于使用DMD的治疗。直接应用DMD办法剖析肿瘤的呼吸运动是不实际的,因为肿瘤是三维的,跨越多个CT切片。预测肺部肿瘤的呼吸运动,开发了一种称为均匀角间隔(UAI)采样的方法来生成相等长度的快照向量,适用于DMD分析。通过将UAI-DMD方法应用于10例肺癌患者的4D-CT数据,证实了这种方法的有效性。结果表明,UAI-DMD方法有效地逼近了肺癌的可变形边界表面和非线性运动轨迹。估计的肿瘤质心在手动描绘的质心的2mm内,与传统的BSpline插值方法相比,误差范围更小,其边缘为3毫米。该方法有可能扩展到基于10期4D-CT数据的动态特征重建肺肿瘤的20期呼吸运动,从而能够更准确地估计计划目标体积(PTV)。
    Due to the high expenses involved, 4D-CT data for certain patients may only include five respiratory phases (0%, 20%, 40%, 60%, and 80%). This limitation can affect the subsequent planning of radiotherapy due to the absence of lung tumor information for the remaining five respiratory phases (10%, 30%, 50%, 70%, and 90%). This study aims to develop an interpolation method that can automatically derive tumor boundary contours for the five omitted phases using the available 5-phase 4D-CT data. The dynamic mode decomposition (DMD) method is a data-driven and model-free technique that can extract dynamic information from high-dimensional data. It enables the reconstruction of long-term dynamic patterns using only a limited number of time snapshots. The quasi-periodic motion of a deformable lung tumor caused by respiratory motion makes it suitable for treatment using DMD. The direct application of the DMD method to analyze the respiratory motion of the tumor is impractical because the tumor is three-dimensional and spans multiple CT slices. To predict the respiratory movement of lung tumors, a method called uniform angular interval (UAI) sampling was developed to generate snapshot vectors of equal length, which are suitable for DMD analysis. The effectiveness of this approach was confirmed by applying the UAI-DMD method to the 4D-CT data of ten patients with lung cancer. The results indicate that the UAI-DMD method effectively approximates the lung tumor\'s deformable boundary surface and nonlinear motion trajectories. The estimated tumor centroid is within 2 mm of the manually delineated centroid, a smaller margin of error compared to the traditional BSpline interpolation method, which has a margin of 3 mm. This methodology has the potential to be extended to reconstruct the 20-phase respiratory movement of a lung tumor based on dynamic features from 10-phase 4D-CT data, thereby enabling more accurate estimation of the planned target volume (PTV).
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  • 文章类型: Journal Article
    患者教育(PE)对于提高患者的知识至关重要,焦虑,和满意,并支持他们的术后恢复。然而,电视胸腔镜手术(VATS)的优势-切口更小,恢复更快-可以缩短住院时间,使体育更具有挑战性的有效实施。多媒体体育可以潜在地增强体育,但其对VATS患者的有效性尚不清楚.
    这项研究为接受VATS(SPE-VATS)的肺肿瘤患者开发了基于场景的PE网络应用程序,以促进PE过程,并通过临床试验评估其可用性。
    SPE-VATS为实验组(EG:32名参与者)提供了交互式场景,查询指导,诊断分析,经验分享,和主动提醒,而对照组(CG:32名参与者)使用小册子和视频。SPE-VATS在术后焦虑减少和患者对应用程序的满意度方面的可用性使用基于状态-特质焦虑清单的自我报告问卷进行评估,技术验收模型,系统可用性量表,和任务负载索引。
    EG和CG在术后焦虑减轻方面无统计学差异,可能是因为90%的参与者接受了低风险的手术类型,和VATS已知在缓解手术焦虑方面是有利的。然而,女性和受教育程度较高的EG参与者表现出与CG相比无显著但有利的降低。此外,EG对该应用程序非常满意(5.0中的4.2至4.4),性别和受教育程度无显著差异。他们特别重视互动场景,经验分享,和SPE-VATS的诊断分析特点。
    SPE-VATS展示了其可用性和高患者满意度,特别是女性和受过高等教育的患者。低危患者优势和VATS的优势可能解释了术后焦虑减轻的非显著性,保证对高危患者的进一步研究,以评估SPE-VATS对临床实践的影响。
    UNASSIGNED: Patient education (PE) is essential for improving patients\' knowledge, anxiety, and satisfaction, and supporting their postoperative recovery. However, the advantages of video-assisted thoracoscopic surgery (VATS)-smaller incisions and faster recovery-can result in shorter hospital stays, making PE more challenging to implement effectively. Multimedia PE can potentially enhance PE, but its effectiveness for patients undergoing VATS is unclear.
    UNASSIGNED: This study developed a scenario-based PE web app for lung tumor patients undergoing VATS (SPE-VATS) to facilitate the PE process and evaluated its usability through a clinical trial.
    UNASSIGNED: The SPE-VATS provided the experimental group (EG: 32 participants) with interactive scenario, query guidance, diagnostic analysis, experience sharing, and active reminder, while the control group (CG: 32 participants) used pamphlets and videos. The usability of SPE-VATS in terms of postoperative anxiety reduction and patient satisfaction with the app was evaluated using self-reported questionnaires based on the state-trait anxiety inventory, technology acceptance model, system usability scale, and task load index.
    UNASSIGNED: There was no statistically significant difference in postoperative anxiety reduction between the EG and CG, possibly because 90% of the participants underwent a low-risk surgical type, and VATS is known to be advantageous in alleviating surgical anxiety. However, females and higher educated EG participants showed a non-significant but favorable reduction than their CG counterparts. Moreover, the EG was highly satisfied with the app (rated 4.2 to 4.4 out of 5.0), with no significant gender and education level difference. They particularly valued the interactive scenario, experience sharing, and diagnostic analysis features of SPE-VATS.
    UNASSIGNED: The SPE-VATS demonstrated its usability and high patient satisfaction, particularly for female and higher educated patients. Low-risk patient predominance and VATS\'s advantages may explain non-significant postoperative anxiety reduction, warranting further studies on high-risk patients to evaluate the impact of SPE-VATS on clinical practice.
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  • 文章类型: Journal Article
    光热疗法(PTT),利用纳米材料收集激光能量并将其转化为热量以消融肿瘤细胞,已迅速发展为肺部肿瘤的治疗,但是大多数与PTT相关的纳米材料是不可降解的,与PTT相关的免疫反应尚不清楚,这导致实际PTT的结果不令人满意。在这里,我们合理设计并制备了一种用于免疫激活PTT的锰离子掺杂的聚多巴胺纳米材料(MnPDA)。首先,MnPDA表现出57.2%的光热转换效率,以实现高效PTT,其次,MnPDA可以通过谷胱甘肽(GSH)刺激释放Mn2+,它可以与过表达的H2O2在Fenton样反应中产生·OH,并刺激干扰素基因的环GMP-AMP合酶刺激物(cGAS-STING)途径。这两者协同作用可以有效清除未被PTT消融的肺肿瘤细胞,在MnPDA的激光照射下,体内的肿瘤抑制率为86.7%,并进一步显著激活下游免疫反应,如细胞毒性T细胞与免疫抑制Treg细胞的比例增加所证明的。最后,GSH可降解MnPDA纳米粒子可用于肺肿瘤的光热治疗和cGAS-STING激活的免疫治疗,为未来肺部肿瘤的治疗提供了新的思路和策略。
    Photothermal therapy (PTT), which utilizes nanomaterials to harvest laser energy and convert it into heat to ablate tumor cells, has been rapidly developed for lung tumor treatment, but most of the PTT-related nanomaterials are not degradable, and the immune response associated with PTT is unclear, which leads to unsatisfactory results of the actual PTT. Herein, we rationally designed and prepared a manganese ion-doped polydopamine nanomaterial (MnPDA) for immune-activated PTT with high efficiency. Firstly, MnPDA exhibited 57.2% photothermal conversion efficiency to accomplish high-efficiency PTT, and secondly, MnPDA can be stimulated by glutathione (GSH) to the release of Mn2+, and it can produce ·OH in a Fenton-like reaction with the overexpressed H2O2 and stimulate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. These two synergistically can effectively remove lung tumor cells that have not been ablated by PTT, resulting in an 86.7% tumor suppression rate under laser irradiation of MnPDA in vivo, and further significantly activated the downstream immune response, as evidenced by an increased ratio of cytotoxic T cells to immunosuppressive Treg cells. Conclusively, the GSH degradable MnPDA nanoparticles can be used for photothermal therapy and cGAS-STING-activated immunotherapy of lung tumors, which provides a new idea and strategy for the future treatment of lung tumors.
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  • 文章类型: Journal Article
    关于在全身性炎症期间离开骨髓的Lin-CD34DNAM-1brightCXCR4+祖细胞的轨迹和发育命运的信息很少。
    为了研究癌症患者的Lin-CD34DNAM-1brightCXCR4细胞循环,表征它们进入受累的肺组织并表征它们的后代。
    对18名肺癌患者的PBMC进行流式细胞术分析,以研究Lin-CD34DNAM-1brightCXCR4+前体。纯化前体(>99%)并从所有患者体外培养。通过流式细胞术分析来自经历肿瘤切除的患者的配对PBMC和组织样品,以评估组织进入并比较两个区室中的Lin-CD34+DNAM-1brightCXCR4+细胞的表型和发育潜力。
    在第一次治疗后20d观察到Lin-CD34+DNAM-1brightCXCR4+前体的显著循环。前体表达CXC3CR1、CXCR3、CXCR1,与向发炎组织行进一致。肺组织样本的流式细胞术分析显示,所有患者的肿瘤和邻近未受累区域均存在前体。从血液和肺组织中成功的纯化和体外培养产生了较小比例的成熟NK细胞(<10%)和主要比例(>85%)的具有先天样表型的表达NKG2D的α/βT后代,NKp30,DNAM-1。先天样成熟的T细胞在体外是细胞毒性的,可以通过NKR/TCR共刺激触发,并显示广谱的Th1,Th2和Th1/Th17细胞因子产生。
    在晚期肺癌中,CD34+DNAM-1brightCXCR4+炎症前体在治疗后增加,进入受累组织,产生功能性后代,因此可能代表了在高度SDF-1/CXCR4偏向的前转移肿瘤微环境中促进免疫平衡的额外参与者。
    There is little information on the trajectory and developmental fate of Lin-CD34+DNAM-1bright CXCR4+ progenitors exiting bone marrow during systemic inflammation.
    To study Lin-CD34+DNAM-1bright CXCR4+ cell circulation in cancer patients, to characterize their entry into involved lung tissue and to characterize their progenies.
    Flow cytometric analysis of PBMC from 18 patients with lung cancer on samples collected immediately before the first and the second treatment was performed to study Lin-CD34+DNAM-1bright CXCR4+ precursors. Precursors were purified (>99%) and cultured in vitro from all patients. Paired PBMC and tissue samples from patients undergoing tumor resection were analyzed by flow cytometry to assess tissue entry and compare phenotype and developmental potential of Lin-CD34+DNAM-1bright CXCR4+ cells in both compartments.
    Significant circulation of Lin-CD34+DNAM-1bright CXCR4+ precursors was observed 20d after the first treatment. Precursors express CXC3CR1, CXCR3, CXCR1 consistent with travel towards inflamed tissues. Flowcytometric analysis of lung tissue samples showed precursor presence in all patients in tumor and neighboring uninvolved areas. Successful purification and in vitro culture from both blood and lung tissue generates a minor proportion of maturing NK cells (<10%) and a predominant proportion (>85%) of α/β T-progenies with innate-like phenotype expressing NKG2D,NKp30,DNAM-1. Innate-like maturing T-cells in vitro are cytotoxic, can be triggered via NKR/TCR co-stimulation and display broad spectrum Th1,Th2 and Th1/Th17 cytokine production.
    In advanced stage lung cancer CD34+DNAM-1brightCXCR4+ inflammatory precursors increase upon treatment, enter involved tissues, generate functional progenies and may thus represent an additional player contributing to immune balance in the highly SDF-1/CXCR4-biased pro-metastatic tumor microenvironment.
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