• 文章类型: Journal Article
    目的:放疗治疗非小细胞肺癌(NSCLC)疗效显著。然而,抗辐射仍然是取得良好成果的主要障碍。本研究旨在确定放射增敏NSCLC的潜在靶点并阐明其潜在机制。
    方法:使用基于慢病毒的感染和CRISPR/Cas9技术来调节microRNA-384(miR-384)的表达。细胞克隆形成测定和异种移植肿瘤模型用于分析NSCLC细胞中的放射敏感性。使用荧光激活的细胞分选来评估细胞周期和细胞死亡。免疫荧光染色,彗星测定,和同源重组或非同源末端连接I-SceI/GFP报告基因测定用于研究DNA损伤和修复。Western印迹和定量实时聚合酶链反应用于鉴定miR-384的靶标。进行染色质免疫沉淀和聚合酶链反应以评估miR-384的上游调节因子。
    结果:MiR-384在非小细胞肺癌中表达下调。miR-384的过表达增加了NSCLC细胞在体外和体内的放射敏感性,而miR-384的敲除导致放射抗性。通过减少G2/M细胞周期阻滞上调miR-384放射致敏NSCLC细胞,抑制DNA损伤修复,并因此增加细胞死亡;miR-384耗竭具有相反的作用。进一步调查显示ATM机,Ku70和Ku80是miR-384的直接靶标。此外,miR-384被NF-κB抑制。
    结论:MiR-384是一种被NF-κB抑制的电离辐射应答基因。MiR-384通过靶向ATM增强NSCLC细胞的放射敏感性,Ku80和Ku70,会损害DNA损伤修复。因此,miR-384可能作为NSCLC的一种新型放射增敏剂。
    OBJECTIVE: Radiotherapy has achieved remarkable effects in treating non-small cell lung cancer (NSCLC). However, radioresistance remains the major obstacle to achieving good outcomes. This study aims at identifying potential targets for radiosensitizing NSCLC and elucidating the underlying mechanisms.
    METHODS: Lentivirus-based infection and CRISPR/Cas9 technology were used to modulate the expression of microRNA-384 (miR-384). Cell clonogenic formation assays and a xenograft tumor model were used to analyze radiosensitivity in NSCLC cells. Fluorescence-activated cell sorting was used to assess the cell cycle and cell death. Immunofluorescence staining, Comet assays, and homologous recombination or non-homologous end-joining I-SceI/GFP reporter assays were used to study DNA damage and repair. Western blotting and quantitative real-time polymerase chain reaction were used to identify the targets of miR-384. Chromatin immunoprecipitation and polymerase chain reaction were performed to evaluate upstream regulators of miR-384.
    RESULTS: MiR-384 was downregulated in NSCLC. Overexpression of miR-384 increased the radiosensitivity of NSCLC cells in vitro and in vivo, whereas knockout of miR-384 led to radioresistance. Upregulation of miR-384 radiosensitized NSCLC cells by decreasing G2/M cell cycle arrest, inhibiting DNA damage repair, and consequently increasing cell death; miR-384 depletion had the opposite effects. Further investigation revealed that ATM, Ku70, and Ku80 were direct targets of miR-384. Moreover, miR-384 was repressed by NF-κB.
    CONCLUSIONS: MiR-384 is an ionizing radiation-responsive gene repressed by NF-κB. MiR-384 enhances the radiosensitivity of NSCLC cells via targeting ATM, Ku80, and Ku70, which impairs DNA damage repair. Therefore, miR-384 may serve as a novel radiosensitizer for NSCLC.
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  • 文章类型: Journal Article
    评估尼妥珠单抗联合放疗或放化疗治疗局部晚期头颈部鳞状细胞癌的疗效和安全性。
    在PubMed上进行了系统搜索,WebofScience,Embase,科克伦图书馆,中国国家知识基础设施,中国生物医学,万方,VIP数据库。通过严格的纳入和排除标准选择了7项符合条件的随机对照试验(n=1012)。
    共1012例。尼妥珠单抗联合治疗组508例(50.2%);对照组504例(49.8%)。荟萃分析结果显示总生存期(危险比[HR]=0.75,95%置信区间[CI]:0.62~0.90,P<0.05),无进展生存期(HR=0.69,95%CI:0.54-0.87,P<0.05),完全缓解率(风险比[RR]=1.52,95%CI:1.24-1.86,P<0.05),与对照组相比,尼妥珠单抗联合治疗组的客观缓解率(RR=1.32,95%CI:1.17-1.48,P<0.05)明显提高。在不良反应的发生率方面,只有尼妥珠单抗联合治疗组的皮疹发生率高于单独治疗组,其余不良反应(中性粒细胞减少,贫血,恶心/呕吐,粘膜炎,皮炎,吞咽困难)。
    尼妥珠单抗联合放疗或放化疗对局部晚期头颈部鳞状细胞癌的疗效优于单纯放疗或放化疗,安全状况是可控的。因此,在治疗中加入尼妥珠单抗有望成为本病的有效治疗选择.然而,需要更多的前瞻性随机对照试验来全面探讨这种治疗对局部晚期头颈部鳞状细胞癌患者的有效性.
    标识符PROSPERO(CRD:42022383313)。
    UNASSIGNED: To assess the efficacy and safety of nimotuzumab in combination with radiotherapy or chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.
    UNASSIGNED: Systematic searches were performed on PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, VIP databases. Seven eligible randomized controlled trials (n = 1012) were selected through rigorous inclusion and exclusion criteria.
    UNASSIGNED: A total of 1012 cases were included. including 508 (50.2%) in the nimotuzumab combination treatment group; There were 504 cases (49.8%) in the control group. The results of meta-analysis showed that the overall survival (Hazard Ratio [HR]=0.75, 95% Confidence Interval [CI]: 0.62-0.90, P<0.05), progression-free survival (HR=0.69, 95% CI: 0.54-0.87, P<0.05), complete response rate (Risk Ratio [RR]=1.52, 95% CI: 1.24-1.86, P<0.05), and objective response rate (RR=1.32, 95% CI: 1.17-1.48, P<0.05) were significantly improved in the nimotuzumab combination treatment group compared with the control group. In terms of the incidence of adverse effects, only the incidence of rash was the nimotuzumab combination group higher than in the treatment alone group, and there was no significant difference between the remaining adverse reactions (neutropenia, anemia, nausea/vomiting, mucositis, dermatitis, dysphagia).
    UNASSIGNED: Nimotuzumab combined with radiotherapy or chemoradiotherapy is more effective than radiotherapy alone or chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck, and the safety profile is controllable. Therefore, the addition of nimotuzumab to treatment is expected to be an effective treatment option for this disease. However, more prospective randomized controlled trials are needed to fully explore the effectiveness of this treatment in patients with locally advanced head and neck squamous cell carcinoma.
    UNASSIGNED: identifier PROSPERO (CRD: 42022383313).
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  • 文章类型: Case Reports
    原发性恶性肿瘤的眼转移发生率较低。主要是,这些原发性恶性肿瘤包括乳腺癌和肺癌。眼部转移癌在临床上常被忽视。在临床实践中,小细胞肺癌(SCLC)很少转移到右眼.通过临床症状监测和眼部辅助检查的早期发现和治疗,对保持患者的视力和提高患者的生活质量具有重要意义。这种治疗包括放射治疗或眼球摘除。一名54岁的男性SCLC患者在使用恩维罗鲁单抗和依托泊苷和顺铂的全身治疗期间,视力下降和视力模糊。经检查,包括眼底摄影,眼B超和磁共振成像,怀疑有右眼转移。在很短的时间内,患者右眼经历了严重的疼痛和失明,这需要手术切除右眼球。术后病理证实有转移。经过六个周期的治疗,肺的原发病灶大小缩小。通过报告这个SCLC转移到右眼的病例,旨在为眼转移癌的临床诊治提供参考。
    The incidence of eye metastasis from primary malignant tumors is low. Predominantly, these primary malignant tumors consist of breast and lung carcinoma. Ocular metastatic carcinoma is often clinically overlooked. In clinical practice, it is rare for small-cell lung carcinoma (SCLC) to metastasize to the right eye. Early detection and treatment via the monitoring of clinical symptoms and auxiliary examinations of the eye are of great significance in preserving the patient\'s vision and improving their quality of life. Such treatments include radiotherapy or enucleation of the eyeball. A 54-year-old male patient with SCLC experienced a decline in vision and blurred vision during his systemic treatment using combined enverolumab and etoposide and cisplatin. Upon examination, including fundus photography, ocular B-scan and magnetic resonance imaging, a right eye metastasis was suspected. Within a short period of time, the patient experienced significant pain and blindness in the right eye, which required surgical removal of the right eyeball. Postoperative pathology confirmed metastasis. After six cycles of treatment, the primary lesion in the lung reduced in size. By reporting this case of SCLC metastasis to the right eye, we aim to provide a reference for the clinical diagnosis and treatment of ocular metastatic carcinoma.
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  • 文章类型: Journal Article
    背景:放疗(RT)的心脏毒性可影响癌症的长期生存率。这已在乳腺癌和淋巴瘤患者中得到证实。然而,很少有研究利用二维斑点追踪超声心动图(2D-STE)来评估影响放射性心脏病(RIHD)的危险因素,缺乏定量数据。因此,我们打算探讨RIHD的危险因素,并使用2D-STE技术对其进行量化.
    方法:我们最终招募了40例接受胸部肿瘤放疗的患者。对于每个病人来说,2D-STE之前完成,during,在RT之后和后续行动中。我们分析了2D-STE在预测RIHD中的敏感性以及RT参数与心脏收缩功能下降之间的关系。
    结果:左心室整体纵向应变(LVGLS),心内膜LVGLS(LVGLS-Endo),心外膜LVGLS(LVGLS-Epi),与治疗前相比,治疗前后右心室游离壁纵向应变(RVFWLS)降低,而传统的参数,如左心室射血分数(LVEF),心脏Tei指数(Tei),三尖瓣环自由壁的收缩期峰值速度(s\')未显示任何变化。治疗后和治疗前之间的LVGLS和LVGLS-Endo值的降低以及降低与基线值的比率与平均心脏剂量(MHD)线性相关(所有P值<0.05)。治疗后和治疗前之间的LVGLS-Epi值的降低以及降低与基线值的比率与暴露于5Gy或更多(V5)的心脏体积的百分比线性相关(P值<0.05)。RVFWLS的降低和降低与基线值的比率与MHD和患者年龄呈线性关系(所有P值<0.05)。终点事件在心脏右侧比在左侧更频繁地发生。56.5岁以上的患者发生右心终点事件的可能性更大。对于心脏左侧和右侧的MHD超过20.2Gy的患者也是如此。
    结论:2D-STE可以比常规超声心动图更早、更灵敏地检测心脏损伤。MHD是左心室收缩功能的重要预后参数,和V5也可能是一个重要的预后参数。MHD和年龄是右心室收缩功能的重要预后参数。
    BACKGROUND: The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology.
    METHODS: We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline.
    RESULTS: Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s\') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart.
    CONCLUSIONS: 2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function.
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  • 文章类型: Journal Article
    目的:本研究旨在比较一线化疗联合放疗与单纯化疗对IVB期食管鳞状细胞癌(ESCC)患者的疗效和安全性。
    方法:我们回顾性检查了409例接受一线化疗和抗PD-1抗体治疗的IVBESCC患者,对原发病灶进行或不进行≥40Gy辐射剂量的放疗,从2018年10月至2022年12月之间的四个学术癌症中心。进行倾向评分匹配(PSM)以最小化潜在的混杂效应。
    结果:在409名患者的总体队列中,接受额外放疗的组的总生存期(OS)(风险比[HR]:0.51,95%置信区间[CI]:0.39~0.66,P<0.001)和无进展生存期(PFS)(HR:0.52,95%CI:0.40~0.66,P<0.001)均优于接受单独化疗的组.1:1PSM后,匹配年龄,肿瘤位置,和转移部位,共选择250例患者进行进一步分析.结果保持一致,并显示放疗的增加显着改善了OS和PFS(中位OS:24.9vs.14.6个月,P=0.003;PFS中位数:14.2vs.10.6个月,P=0.002)。多因素Cox分析包括肿瘤位置,T级,转移部位,和治疗方式,显示放疗是OS(HR:0.57,95%CI:0.41-0.81)和PFS(HR:0.63,95%CI:0.47-0.86)的独立预后因素。亚组分析显示,仅接受放疗的非区域淋巴结转移患者的OS显着延长(HR:0.49,95%CI:0.34-0.70)。在有远处器官转移的患者中没有观察到OS生存获益(HR:0.72,95%CI:0.46-1.13)。关于安全,接受额外放疗组的3-4级淋巴细胞减少发生率较高(74.4%vs.17.7%,P<0.001)和食管炎(11.2%vs.2.4%,P=0.006)。
    结论:在化学免疫疗法中增加放疗可改善非区域淋巴结转移的IVBESCC患者的生存率。
    OBJECTIVE: This study aimed to compare the efficacy and safety of combining first-line chemoimmunotherapy with radiotherapy versus chemoimmunotherapy alone in patients with stage IVB esophageal squamous cell carcinoma (ESCC).
    METHODS: We retrospectively examined 409 patients with stage IVB ESCC who received first-line chemotherapy and anti-PD-1 antibody, with or without radiotherapy of ≥ 40 Gy radiation dose to primary lesion, from four academic cancer centers between October 2018 and December 2022. Propensity score matching (PSM) was conducted to minimize the potential confounding effects.
    RESULTS: In the overall cohort of 409 patients, the group that received additional radiotherapy had superior overall survival (OS) (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.39-0.66, P < 0.001) and progression-free survival (PFS) (HR: 0.52, 95% CI: 0.40-0.66, P < 0.001) compared to the group that received chemoimmunotherapy alone. After 1:1 PSM, matching age, tumor location, and metastatic sites, a total of 250 patients were selected for further analysis. The results remained consistent and showed that the addition of radiotherapy significantly improved OS and PFS (median OS: 24.9 vs. 14.6 months, P = 0.003; median PFS: 14.2 vs. 10.6 months, P = 0.002). Multivariate Cox analysis including tumor location, T stage, metastatic sites, and treatment modality, revealed that radiotherapy was an independent prognostic factor for both OS (HR: 0.57, 95% CI: 0.41-0.81) and PFS (HR: 0.63, 95% CI: 0.47-0.86). Subgroup analyses revealed significant OS prolongation in patients with non-regional lymph node metastases only who received radiotherapy (HR: 0.49, 95% CI: 0.34-0.70). No OS survival benefit was observed in those with distant organ metastases (HR: 0.72, 95% CI: 0.46-1.13). Regarding safety, the group receiving additional radiotherapy had higher incidences of grade 3-4 lymphopenia (74.4% vs. 17.7%, P < 0.001) and esophagitis (11.2% vs. 2.4%, P = 0.006).
    CONCLUSIONS: The addition of radiotherapy to chemoimmunotherapy improved the survival of stage IVB ESCC patients with non-regional lymph nodes metastasis.
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  • 文章类型: Case Reports
    甲状腺样滤泡性肾细胞癌(TLFRCC),也称为甲状腺样滤泡状癌或甲状腺滤泡状癌,是一种非常罕见的肾细胞癌变体,最近才被承认。这种肿瘤表现出与甲状腺相似的独特滤泡形态。免疫组织化学分析显示PAX8,波形蛋白,和EMA,而甲状腺特异性标志物TG和TTF1始终不存在。此外,在临床评估中,明显没有并发甲状腺病理.以前的报道表明,TLFRCC是一种惰性物质,生长缓慢的恶性肿瘤,具有罕见的转移潜力。在这份报告中,我们介绍了一个以显著骨化和广泛转移为特征的TLFRCC病例,包括多灶性肺部病变,腹壁受累,渗入腰大肌.据我们所知,这只是甲状腺滤泡性肾癌远处转移的第三例。目前的病例证明了一种将放疗与托里帕利马结合的治疗方法,程序性细胞死亡1(PD-1)受体抑制剂,还有帕唑帕尼.这种治疗方案是根据全面的基因组图谱定制的,鉴定了POLE(DNA聚合酶epsilon的催化亚基)和ATM(共济失调-毛细血管扩张症突变)基因的突变,两者都与各种恶性肿瘤的发病机理有关。这些发现代表了一个新的发现,这样的突变从未报道过与TLFRCC相关。到目前为止,这种治疗方法已被证明是治疗转移性TLFRCC最有效的选择,这也标志着首次提到放射治疗在治疗这种特殊亚型肾细胞癌方面的潜在益处。
    Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.
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  • 文章类型: Journal Article
    The simultaneous objectives of destroying tumor cells while protecting normal pelvic organs present a dual clinical and technical challenge within the realm of pelvic tumor radiotherapy. This article reviews the latest literatures, focusing on technological innovations in key aspects of radiotherapy such as positioning, planning, and delivery. These include positioning fixation techniques, organ-at-risk avoidance irradiation, non-coplanar irradiation techniques, as well as organ displacement protection and image-guided adaptive techniques. It summarizes and discusses the research progress made in the protection of critical organs during pelvic tumor radiotherapy. The paper emphasizes technological advancements in the protection of critical organs throughout the processes of radiotherapy positioning, planning, and implementation, aiming to provide references for further research on the protection of critical organs in the external irradiation treatment of pelvic tumors.
    如何在摧毁肿瘤细胞的同时保护盆腔内的正常器官,是盆腔肿瘤放射治疗领域在临床和技术上面临的双重挑战。本文通过评述最新文献,聚焦于放疗定位、计划设计、实施等关键环节中的技术创新,包括:摆位固定技术、危及器官避让照射技术和非共面照射技术,以及器官移位保护和图像引导的自适应技术等,总结并讨论了盆腔肿瘤放疗中危及器官保护的研究进展。本文重点关注放疗定位、计划设计、实施各环节中危及器官保护的技术进展,旨在为盆腔肿瘤外照射放疗中危及器官保护的进一步研究奠定基础。.
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  • 文章类型: Journal Article
    通过治疗方案抑制肿瘤微环境中的免疫应答可以阻碍肿瘤的根除,可能导致肿瘤转移。作为一种非侵入性的治疗方法,放射治疗用于肿瘤消融。在这项研究中,我们的目的是提高放疗的治疗效果和触发免疫反应,通过制定一个苯并噻唑(BTS)-亚磺酸酯(BTS)-负载融合脂质体(BFL)纳米平台,然后与放疗相结合进行抗癌治疗。血小板细胞膜,配备独特的表面受体,使BFL能够有效地靶向肿瘤,同时逃避免疫系统并粘附于肿瘤细胞。这有助于BFL被癌细胞吞噬,随后释放其中的BTS。发布后,BTS生产二氧化硫(SO2)用于气体治疗,启动细胞内谷胱甘肽(GSH)的氧化。这个过程证明了在放射治疗后修复损伤的有效性,从而实现有效的放射增敏。揭示了在BFL促进的增强的放射增敏作用后触发了免疫应答。这种方法促进了淋巴结内树突状细胞(DC)的成熟,导致远端肿瘤中T细胞比例增加。这导致原发性肿瘤的显著根除和远处肿瘤生长的抑制。总之,个性化BFL与放疗的整合显示出增强肿瘤免疫反应和消除肿瘤的潜力,包括转移。
    The inhibition of the immune response in the tumor microenvironment by therapy regimens can impede the eradication of tumors, potentially resulting in tumor metastasis. As a non-invasive therapeutic method, radiotherapy is utilized for tumor ablation. In this study, we aimed to improve the therapeutic impact of radiotherapy and trigger an immune response by formulating a benzothiazole sulfinate (BTS)-loaded fusion liposome (BFL) nanoplatform, which was then combined with radiotherapy for anti-cancer treatment. The platelet cell membrane, equipped with distinctive surface receptors, enables BFL to effectively target tumors while evading the immune system and adhering to tumor cells. This facilitates BFL\'s engulfment by cancer cells, subsequently releasing BTS within them. Following the release, the BTS produces sulfur dioxide (SO2) for gas therapy, initiating the oxidation of intracellular glutathione (GSH). This process demonstrates efficacy in repairing damage post-radiotherapy, thereby achieving effective radiosensitization. It was revealed that an immune response was triggered following the enhanced radiosensitization facilitated by BFL. This approach facilitated the maturation of dendritic cell (DC) within lymph nodes, leading to an increase in the proportion of T cells in distant tumors. This resulted in significant eradication of primary tumors and inhibition of growth in distant tumors. In summary, the integration of personalized BFL with radiotherapy shows potential in enhancing both tumor immune response and the elimination of tumors, including metastasis.
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  • 文章类型: Journal Article
    放射治疗对于治疗结直肠癌(CRC)至关重要,尤其是晚期直肠癌.然而,CRC细胞的低放射敏感性极大地限制了放疗疗效。小核仁RNA(snoRNAs)是一类非编码RNA,主要指导核糖体RNA(rRNAs)的转录后修饰,小核RNA(snRNA),和其他细胞RNA。虽然snoRNAs参与肿瘤进展和化疗耐药,它们与放射敏感性的关联在很大程度上仍然未知.在这里,SNORA28在CRC中高表达,与不良预后呈正相关。此外,SNORA28过表达在体外和体内增强CRC细胞的生长和放射抗性。机械上,SNORA28充当分子诱饵,募集含溴结构域的蛋白4(BRD4),这增加了LIFR启动子区的H3K9乙酰化水平。这刺激LIFR转录,进而触发JAK1/STAT3通路,增强CRC细胞的增殖和放射抗性。总的来说,这些结果突出了snoRNAs调节肿瘤细胞放射敏感性和影响靶基因启动子区组蛋白乙酰化修饰的能力,从而拓宽了目前对snoRNA生物学功能和靶基因调控机制的认识。
    Radiotherapy is essential for treating colorectal cancer (CRC), especially in advanced rectal cancer. However, the low radiosensitivity of CRC cells greatly limits radiotherapy efficacy. Small nucleolar RNAs (snoRNAs) are a class of noncoding RNA that primarily direct post-transcriptional modifications of ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs), and other cellular RNAs. While snoRNAs are involved in tumor progression and chemoresistance, their association with radiosensitivity remains largely unknown. Herein, SNORA28 is shown highly expressed in CRC and is positively associated with poor prognosis. Furthermore, SNORA28 overexpression enhances the growth and radioresistance of CRC cells in vitro and in vivo. Mechanistically, SNORA28 acts as a molecular decoy that recruits bromodomain-containing protein 4 (BRD4), which increases the level of H3K9 acetylation at the LIFR promoter region. This stimulates LIFR transcription, which in turn triggers the JAK1/STAT3 pathway, enhancing the proliferation and radioresistance of CRC cells. Overall, these results highlight the ability of snoRNAs to regulate radiosensitivity in tumor cells and affect histone acetylation modification in the promoter region of target genes, thus broadening the current knowledge of snoRNA biological functions and the mechanism underlying target gene regulation.
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  • 文章类型: Journal Article
    非侵入性抗肿瘤治疗可以治疗不能耐受手术或不适合手术的肿瘤患者。然而,非侵袭性抗肿瘤治疗所引起的心脏毒性和肿瘤耐药严重影响患者的生活质量和预后。作为一种从草药中提取的多酚,姜黄素具有多种药理作用,如抗炎,抗氧化,抗肿瘤,等。姜黄素通过直接促进肿瘤细胞死亡和降低肿瘤细胞的侵袭能力发挥抗肿瘤作用。姜黄素主要通过抑制核因子-κB(NF-κB)信号通路发挥治疗作用,抑制环氧合酶-2(COX-2)的产生,促进caspase-9的表达,并直接诱导肿瘤细胞中活性氧(ROS)的产生。姜黄素纳米粒子可以解决姜黄素的缺点,如水溶性差和高代谢率,可有效用于抗肿瘤治疗。姜黄素纳米粒作为佐剂可改善肿瘤患者的预后和生活质量,增强肿瘤对非侵入性治疗的敏感性,减少副作用。尤其是心脏毒性.在本文中,我们收集和分析相关数据库的文献。指出今后对姜黄素的研究倾向于缓解治疗引起的不良反应,这对肿瘤患者更有意义。
    Non-invasive antitumor therapy can treat tumor patients who cannot tolerate surgery or are unsuitable. However, tumor resistance to non-invasive antitumor therapy and cardiotoxicity caused by treatment seriously affect the quality of life and prognosis of patients. As a kind of polyphenol extracted from herbs, curcumin has many pharmacological effects, such as anti-inflammation, antioxidation, antitumor, etc. Curcumin plays the antitumor effect by directly promoting tumor cell death and reducing tumor cells\' invasive ability. Curcumin exerts the therapeutic effect mainly by inhibiting the nuclear factor-κB (NF-κB) signal pathway, inhibiting the production of cyclooxygenase-2 (COX-2), promoting the expression of caspase-9, and directly inducing reactive oxygen species (ROS) production in tumor cells. Curcumin nanoparticles can solve curcumin\'s shortcomings, such as poor water solubility and high metabolic rate, and can be effectively used in antitumor therapy. Curcumin nanoparticles can improve the prognosis and quality of life of tumor patients by using as adjuvants to enhance the sensitivity of tumors to non-invasive therapy and reduce the side effects, especially cardiotoxicity. In this paper, we collect and analyze the literature of relevant databases. It is pointed out that future research on curcumin tends to alleviate the adverse reactions caused by treatment, which is of more significance to tumor patients.
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