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关键词： 类器官   患者来源类器官   肿瘤微环境   免疫治疗   高通量测序  

摘要： 类器官(organoids)是一种体外三维细胞培养技术,能够在一定程度上模拟组织结构与关键生物学特性。患者来源类器官(patient-derived organoids, PDOs)已成为研究肿瘤异质性和肿瘤微环境的的重要模型,在肿瘤发病机制、药物筛选和精准医疗中应用广泛。联合免疫治疗通过整合免疫检查点抑制剂、靶向治疗和化疗等多种手段,协同激活机体自身免疫,成为癌症治疗的重要突破。而类器官与高通量测序的的结合进一步推动了从机制解析到个体化治疗方案优化的转化应用。类器官技术在多领域的应用及其与前沿治疗策略、测序技术的协同发展,正持续推动肿瘤精准医疗向高效化、个体化方向迈进,为癌症研究与临床转化提供新的理论基础与实践路径。

关键词： 滋阴   肿瘤   中医药   理论创新  

摘要： 恶性肿瘤的防治是现代医学面临的重大挑战,中医药在减轻放化疗不良反应、防止复发方面展现出独特优势,但亟需精准的辨治框架以提升疗效。本团队基于深厚的中医经典理论积淀与长期临证经验,将“滋阴”这一治法应用在恶性肿瘤防治中,提出了一个基于六经辨证的、针对现代病机特点的全新应用范式与理论阐释。该文旨在钩玄滋阴学说思想精髓,首先从文字、哲学、医学三方面追溯“滋阴”本义与内涵,系统梳理其从秦汉萌芽、金元确立到明清深化的学术发展史。进而重点阐释本团队滋阴理论的核心内容:在生理上厘清“阴气”“阴精”“阴液”的体用关系;在病理上提出现代人群“阴虚为本,夹杂他邪”的核心病机;在辨治上构建“以六经为纲,以滋阴为法”的精准诊疗体系。最后,探讨该思想在恶性肿瘤防治中作为“扶正抗癌”核心策略的具体应用,以期为中医肿瘤诊疗提供新的理论借鉴和临床范式。

关键词： Colitis related colorectal cancer   Colitis, ulcerative   Matrix Gla protein   Vitamin K2  

摘要： Objective To explore the mechanism of vitamin K2 (VitK2) regulating matrix Gla protein (MGP) in inhibiting tumor growth in inflammation-associated colorectal cancer (CAC) model mice. Methods Twenty-six C57BL/6 male mice, 6-8 weeks old and weighing 20-25 g, were divided into 4 groups according to the random number table method (each group received different treatments): normal group (treated with olive oil gavage and physiological saline intraperitoneal injection) (n=5), model group [treated with olive oil gavage, azoxymethane (AOM) intraperitoneal injection, and dextran sulfate sodium (DSS) solution drinking treatment)] (n=5), 30 mg group (treated with 30 mg·kg^-1·d^-1 of vitamin K2 gavage, AOM intraperitoneal injection, and DSS solution drinking treatment) (n=8), and 60 mg group (treated with 60 mg·kg^-1·d^-1 of vitamin K2 gavage, AOM intraperitoneal injection, and DSS solution drinking treatment) (n=8). The mice were sacrificed at the end of the 12th week, and the number and length diameter of colon tumors in each group were compared. The expression level of nuclear proliferation antigen (Ki-67) in colon tissues was assessed by immunohistochemistry (IHC), while the levels of MGP protein and Smad1/5 pathway-associated proteins were determined by Western blotting (WB). Additionally, the expression of MGP mRNA was quantified using real-time quantitative PCR (RT-qPCR). According to different treatment methods, colon cancer epithelial cell line SW480 cells were divided into control group [treated with dimethyl sulfoxide (DMSO)], 100 μmol/L group (treated with 100 μ mol/L VitK2), 200 μmol/L group (treated with 200 μ mol/L VitK2), 400 μmol/L group (treated with 400 μ mol/L VitK2), empty vector group (SW480 cells were transfected with empty plasmid) and MGP overexpressing group (SW480 cells were transfected with MGP overexpressing plasmid). After 48 hours of treatment, the expression of MGP protein, changes in the Smad1/5 pathway, a

关键词： 卵巢肿瘤结构域去泛素化酶4   去泛素化酶   DNA损伤修复   应激颗粒   炎症和免疫调控   肿瘤  

摘要： 蛋白酶体介导的蛋白质降解系统依赖于泛素及泛素连接酶E3等相关因子,实现对底物蛋白质的选择性降解;而去泛素化酶(deubiquitylating enzymes, DUBs)则通过去除泛素修饰维持底物蛋白质的稳定性。卵巢肿瘤结构域去泛素化酶4(ovarian tumor domain-containing deubiquitinase 4, OTUD4)是去泛素化酶家族成员之一,能够特异性识别并水解多种泛素链类型,在维持细胞稳态和调控多条信号通路中发挥关键作用。近年的研究表明,OTUD4参与多种生物学过程,包括DNA损伤修复、应激颗粒(stress granules, SGs)形成以及免疫与炎症信号调控。在DNA损伤应答中,OTUD4通过去除靶蛋白质上的多聚泛素链修饰,稳定关键修复因子,从而促进同源重组修复和基因组完整性维持。在细胞遭受环境或代谢应激时,OTUD4参与应激颗粒的动态调控,影响mRNA代谢及蛋白质稳态。在免疫与炎症反应中,OTUD4使底物蛋白质去泛素化,稳定其表达并调节先天免疫信号通路的活化,从而影响抗病毒反应、肿瘤免疫逃逸及炎症进程。值得注意的是,OTUD4的异常表达与多种疾病密切相关,包括病毒感染、自身免疫性疾病及多种肿瘤,提示其可能成为潜在的治疗靶点。本文将系统综述OTUD4的分子机制与生物学功能,阐述其蛋白结构特征、底物识别与去泛素化调控机制,梳理OTUD4在细胞周期调控、DNA损伤修复、免疫应答及肿瘤发生发展等关键生理病理过程中的作用,以期为深入理解其在疾病发生发展中的作用及药物开发提供理论基础。

关键词： Antibody conjugated drugs   Immune checkpoint inhibitor   Oral adverse reactions   Targeted drugs   Tumors  

摘要： Objective To analyze the clinical characteristics of oral adverse reactions associated with novel anti-tumor drugs, providing references for early diagnosis and treatment to improve cancer patients′ qualities of life and therapeutic efficacies. Methods Clinical data and photographs of 11 tumor patients treated at Beijing Hospital from January 2020 to April 2025, who developed oral adverse reactions after receiving targeted therapy, antibody-drug conjugates (ADC), or immune checkpoint inhibitor (ICI), were collected. A retrospective analysis was conducted to summarize the clinical characteristics of these oral adverse reactions. Results Among the 11 patients with oral adverse reactions related to novel anti-tumor drugs, 3 patients received targeted therapy alone, 1 patient received ADC alone, 1 patient received a combination of targeted therapy and ADC, and 6 patients were treated with ICI alone. The time from the first administration of the novel anti-tumor drug to the onset of oral adverse reactions ranged from 0.5 to 18.0 months. The clinical manifestations of oral adverse reactions were various, with oral mucositis (9 cases) being the most common, followed by xerostomia (7 cases), oral candidiasis (4 cases,), hemangioma (1 case), and exacerbation of a pre-existing condition (vitiligo, 1 case). Most adverse reactions were graded as level 2 (moderate), with one case at grade 1 (mild) and one case at grade 3 (severe). Five patients experienced concomitant cutaneous adverse reactions, including 1 patient on targeted therapy, 1 on combined targeted therapy and ADC, and 3 on ICI, presenting mainly as xerosis cutis, maculopapular rash, folliculitis-like rash, and paronychia. For the 10 patients with common terminology criteria for adverse events grade 2 or higher, local administration of corticosteroids and antifungal medications were provided. Severe cases received systemic medication along with comprehensive supportive treatment. Symptoms in all patients were alleviat

关键词： 口腔鳞状细胞癌   微流控芯片   血管内皮细胞   共培养  

摘要： 目的 构建口腔鳞状细胞癌-血管内皮细胞共培养的微流控芯片,验证两种细胞的相互作用,并将芯片用于测试化疗药与抗血管生成药物的疗效。方法 设计以多孔聚对二甲苯膜分隔的双层聚二甲基硅氧烷(PDMS)芯片,上下腔室分别接种人脐静脉内皮细胞(HUVEC)和人舌鳞癌细胞(WSU-HN6)。进行流体力学分析,计算芯片内的相对压力、流速和剪切力。对上层HUVEC与下层HN6细胞分别设置单独培养及二者共培养的条件。将HUVEC分为单独培养组(即对照组)与在芯片下层添加HN6细胞的共培养组(即共培养组)。将HN6细胞也分为单独培养组(即对照组)与在芯片上层添加HUVEC细胞的共培养组(即共培养组)。采用qRT-PCR检测两组HUVEC的血管内皮生长因子(VEGF)、细胞间黏附分子1(ICAM-1)、白细胞介素8(IL-8) mRNA表达水平;免疫荧光染色检测VE-钙黏蛋白(VE-cadherin)的表达情况,跨细胞电阻检测HUVEC屏障功能,血管形成实验检测HUVEC的成管能力。采用CCK-8试剂盒检测HN6细胞活力,qRT-PCR检测HN6的VEGF、碱性成纤维细胞生长因子(bFGF)、N-钙黏蛋白(N-cadherin)、E-钙黏蛋白(E-cadherin)、波形蛋白(Vimentin) mRNA表达水平,免疫荧光染色检测上皮-间充质转化相关标志物表达情况,划痕实验检测HN6细胞迁移能力,TUNEL染色检测HN6细胞凋亡情况。结果 芯片入口培养基流速设为100 μm/s,可模拟生理状态下的流动条件。共培养组HUVEC的VEGF和ICAM-1 mRNA表达水平明显升高(P<0.01),血管形成实验连接点数(P<0.05)和小管总长度(P<0.01)明显增加,跨细胞电阻降低,VE-cadherin形态不完整。qRT-PCR检测结果显示,与单独培养的HN6细胞相比,共培养组HN6细胞活力无明显变化,VEGF、N-cadherin mRNA表达水平明显升高(P<0.05),E-cadherin mRNA表达水平明显降低(P<0.05)。免疫荧光染色显示,上皮-间充质转化(EMT)相关标志物的蛋白表达变化与qRT-PCR结果一致,Vimentin(P<0.001)、N-cadherin(P<0.01)蛋白表达水平明显升高,E-cadherin蛋白表达水平明显降低(P<0.05)。共培养组HN6细胞24 h划痕愈合率明显大于单独培养组(P<0.01),添加贝伐珠单抗可抑制细胞迁移(P<0.0001)且后者浓度越高、抑制作用越强。贝伐珠单抗对HN6细胞没有杀伤作用,也不能改变其对化疗药物的敏感性。结论 本研究设计的双层微流控芯片可模拟HN6与HUVEC的相互作用,进而用于药物筛选。

关键词： 天然有机纳米材料   肿瘤治疗   肿瘤诊断   药物递送   肿瘤微环境  

摘要： 近年来, 肿瘤严重威胁人类生命健康, 传统治疗手段虽广泛应用, 却存在明显局限。为此, 研究者日益聚焦纳米技术, 致力于发展更高效、精准的治疗策略。天然纳米材料, 包括天然存在的纳米颗粒、基于天然产物的大分子纳米材料, 以及源自天然小分子物质的自组装纳米材料, 凭借其独特的理化特性与优良生物相容性, 在医药领域展现出广阔前景。本文重点综述了几类代表性天然有机纳米材料在肿瘤诊断与治疗中的研究进展和应用潜力。展望未来, 天然纳米材料不仅将推动肿瘤诊疗技术革新, 为纳米医学注入绿色、可持续理念, 更有望促进临床转化, 为患者提供更安全、有效的治疗方案。

关键词： 脑肿瘤   高频不可逆电穿孔(HF-IRE)   电场强度   肿瘤消融   磁共振成像(MRI)   肿瘤疗效   安全性评估  

摘要： 目的 旨在评估高频不可逆电穿孔(High Frequency-Irreversible Electroporation,HF-IRE)消融荷原位脑肿瘤大鼠的安全性及部分有效性,为临床转化提供关键参数依据。方法 建立大鼠原位脑肿瘤模型,采用900/1200/1500 V/cm三梯度电场强度实施HF-IRE治疗。通过磁共振成像动态监测肿瘤体积,结合苏木精-伊红染色(Hematoxylin-Eosin Staining,H&E)法和TdT介导的dUTP缺口末端标记法(TUNEL)评估脑组织病理损伤及细胞凋亡,从而系统评估安全性及有效性。结果 术中HF-IRE系统运行稳定,无设备异常。HF-IRE组红细胞、血小板术后上升,对照组术后14天下降。2组天门冬氨酸氨基转移酶差异无统计学意义(P>0.05);丙氨酸氨基转移酶、碱性磷酸酶术后升高(P<0.05),14天恢复。2组均呈急性期炎症反应,病理强度差异无统计学意义(P>0.05)。术后14天,1500 V/cm组凋亡评分高于900、1200 V/cm组(F=7.038,P=0.046)。尼氏染色显示,术后3天2组均见少量神经元损伤;HF-IRE组3天损伤略高于14天。14天评分提示900、1200 V/cm安全性较高,1500 V/cm可能致消融区神经元轻度损伤。结论 1200 V/cm是HF-IRE治疗脑肿瘤的最佳平衡参数,可在保证显著抑瘤效果(>90%)的同时,将HF-IRE引起的不良反应和神经损伤风险降至最低。

关键词： COPPS   COPPS   Gene mutation   Metastasis   Paraganglioma   Recurrence   Whole-exome sequencing  

摘要： Objective To score pheochromocytoma and paraganglioma (PPGL) by using the composite pheochromocytoma and paraganglioma grading system (COPPS), to analyze the correlations of COPPS, the pheochromocytoma of the adrenal gland scaled score (PASS), and the grading system for adrenal pheochromocytoma and paraganglioma (GAPP) with tumor metastasis or recurrence and to explore the relationship between gene mutations and metastasis or recurrence in some PPGL. Methods Clinicopathological data of the 186 paragangliomas diagnosed from January 2012 to December 2022 at Beijing Friendship Hospital, Beijing, China, the Peking University Third Hospital, Beijing, China, and the First Affiliated Hospital of Shihezi University, Shihezi, China were collected and analyzed. Predictive values of the three systems for tumor metastasis or recurrence were evaluated. Immunohistochemistry was performed using the EnVision staining method. Whole-exome sequencing was used to detect gene mutations in 15 tumors. Results Among the 186 PPGL patients, there were 93 females and 93 males, age 49 (47, 50) years old. Metastasis or recurrence occurred in 60 cases. 34 of the tumors were located in the retroperitoneum. The maximum tumor diameter was >7 cm in 42 cases. A COPPS score ≥3 was observed in 97 cases (52.2%, 97/186), among whom 53 cases (54.6%, 53/97) experienced metastasis or recurrence. The metastasis/recurrence rate in the COPPS score≥3 group was significantly higher than that in the <3 group (χ²=46.469,P<0.001). Tumor location in the retroperitoneum, presence of large nests of cells, pathological mitosis, spindle cells, capsular invasion, and fat infiltration were all associated with a COPPS score ≥3 (χ²=18.370, 51.730, 8.914,18.750, 62.481, 19.354, all P<0.05). The sensitivity of COPPS for predicting metastasis/recurrence was 88.3% (53/60), while the specificity was 65.1% (82/126). Negative expression of SDHB was observed in 50 cases, and negative expression of S-100 protei

关键词： 甘草酸   恶性肿瘤   作用机制   联合用药   安全性   临床转化  

摘要： 恶性肿瘤发病率与病死率居高不下,临床化疗药物存在耐药性强、不良反应显著等局限,中药来源小分子化合物凭借多靶点、低毒性优势成为抗肿瘤研究热点。甘草酸作为甘草的核心活性成分,属于齐墩果烷类五环三萜皂苷,在甘草中含量达5%~11%,其抗肿瘤活性已在多系统肿瘤中得到验证,作用机制涵盖阻滞细胞周期、诱导肿瘤细胞凋亡、抑制肿瘤血管生成、阻断侵袭转移、调节肿瘤免疫微环境、减轻慢性炎症等关键环节。在应用价值方面,甘草酸与丹参酮ⅡA、顺铂等中西药联用能实现增效减毒、靶向递送及耐药逆转,兼具药物与载体的双重价值。该文系统综述甘草酸的抗肿瘤药理活性、作用机制、联合用药价值及安全性特征,解析核心调控枢纽的网络机制,分析当前研究局限性并提出针对性临床转化策略,为甘草酸从基础研究向临床应用转化提供参考,也为中药小分子化合物的抗肿瘤开发提供范例。