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NAD+metabolism:pathophysiologic mechanisms and therapeutic potential

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Signal Transduction and Targeted Therapy 2020年第1期5卷 596-632页

作者： Na Xie Lu Zhang Wei Gao Canhua Huang Peter Ernst Huber Xiaobo Zhou Changlong Li Guobo Shen bingwen zou State Key Laboratory of Biotherapy and Cancer Center West China Hospitaland West China School of Basic Medical Sciences&Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu 610041China State Key Laboratory of Biotherapy and Cancer Center West China Hospitaland Collaborative Innovation Center for BiotherapyChengdu 610041China School of Basic Medical Sciences Chengdu University of Traditional Chinese MedicineChengduSichuan 611137China CCU Molecular and Radiation Oncology German Cancer Research CenterDepartment of Radiation OncologyHeidelberg University HospitalHeidelbergGermany First Department of Medicine Medical Faculty MannheimUniversity of HeidelbergTheodor-Kutzer-Ufer 1-368167 MannheimGermany West China School of Basic Medical Sciences&Forensic Medicine West China HospitalSichuan UniversityChengdu 610041China Department of Thoracic Oncology and Department of Radiation Oncology Cancer CenterWest China HospitalSichuan UniversityChengdu 610041Chin

Nicotinamide adenine dinucleotide(NAD^(+))and its metabolites function as critical regulators to maintain physiologic processes,enabling the plastic cells to adapt to environmental changes including nutrient perturbation,genotoxic factors,circadian disorder,infection,inflammation and *** effects are mainly achieved by the driving effect of NAD^(+)on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction ***,multiple NAD^(+)-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA,RNA and proteins,or releasing second messenger cyclic ADPribose(cADPR)and NAADP^(+).Prolonged disequilibrium of NAD^(+)metabolism disturbs the physiological functions,resulting in diseases including metabolic diseases,cancer,aging and neurodegeneration *** this review,we summarize recent advances in our understanding of the molecular mechanisms of NAD^(+)-regulated physiological responses to stresses,the contribution of NAD^(+)deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.

关键词： metabolism therapeutic potential

Polydopamine-coated i-motif DNA/Gold nanoplatforms for synergistic photothermal-chemotherapy

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Asian Journal of Pharmaceutical Sciences 2023年第2期18卷 49-60页

作者： Bo Chen Lan Mei Rangrang Fan Di Chuan Yangmei Ren Min Mu Haifeng Chen bingwen zou Gang Guo State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengdu 610041China Department of Neurosurgery West China HospitalSichuan UniversityChengdu 610041China Department of Thoracic Oncology and Department of Radiation Oncology Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

The combination of photothermal therapywith chemotherapy has gradually developed into promising cancer ***,a synergistic photothermal-chemotherapy nanoplatform based on polydopamine(PDA)-coated gold nanoparticles(AuNPs)were facilely achieved via the in situ polymerization of dopamine(DA)on the surface of *** nanoplatform exhibited augmented photothermal conversion efficiency and enhanced colloidal stability in comparison with uncoated PDA shell *** i-motif DNA nanostructure was assembled on PDA-coated AuNPs,which could be transformed into a C-quadruplex structure under an acidic environment,showing a characteristic pH *** PDA shell served as a linker between the AuNPs and the i-motif DNA *** enhance the specific cellular uptake,the AS1411 aptamer was introduced to the DNA nanostructure employed as a targeting *** addition,Dox-loaded NPs(DAu@PDA-AS141)showed the pH/photothermal-responsive release of *** photothermal effect of DAu@PDA-AS141 elicited excellent photothermal performance and efficient cancer cell inhibition under 808 nm near-infrared(NIR)***,these results demonstrate that the DAu@PDA-AS141 nanoplatform shows great potential in synergistic photothermal-chemotherapy.

关键词： Gold nanoparticles Polydopamine i-motif AS1411 aptamer Photothermal-chemotherapy

Boosting ferroptosis and microtubule inhibition for antitumor therapy via a carrier-free supermolecule nanoreactor

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Journal of Pharmaceutical Analysis 2023年第1期13卷 99-109页

作者： Min Mu Xiaoyan Liang Na Zhao Di Chuan Bo Chen Shasha Zhao Guoqing Wang Rangrang Fan bingwen zou Bo Han Gang Guo State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengdu610041China Key Laboratory of Xinjiang Phytomedicine Resource and Utilization Ministry of EducationSchool of PharmacyShihezi UniversityShiheziXinjiang832002China Department of Neurosurgery West China HospitalSichuan UniversityChengdu610041China Department of Radiation Oncology Cancer CenterWest China HospitalSichuan UniversityChengdu610041China

Traditional microtubule inhibitors fail to significantly enhance+e effect of colorectal cancer;hence,new and efficient strategies are ***+is study,a supramolecular nanoreactor(DOC@TA-Fe^(3+))based on tannic acid(TA),iron ion(Fe^(3+)),and docetaxel(DOC)wi+microtubule inhibition,reactive oxygen species(ROS)generation,and gluta+ione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis *** internalization by CT26 cells,+e DOC@TA-Fe^(3+)nanoreactor escapes from+e lysosomes to release payloads.+e subsequent Fe^(3+)/Fe^(2+)conversion mediated by TA reducibility can trigger+e Fenton reaction to enhance+e ROS ***,Fe^(3+)can consume gluta+ione to repress+e activity of GPX4 to induce ***,+e released DOC controls microtubule dynamics to activate+e apoptosis pa+way.+e superior in vivo antitumor efficacy of DOC@TA-Fe^(3+)nanoreactor in terms of tumor grow+inhibition and improved survival is verified in CT26 tumor-bearing mouse model.+erefore,+e nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer+erapy.

关键词： Carrier-free nanoreactor Ferroptosis Microtubule Colorectal cancer

Radiotherapy-induced heart disease:a review of the literature

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Precision Clinical Medicine 2019年第4期2卷 270-282页

作者： bingwen zou Julius Philipp Schuster Kerun Niu Qianyi Huang Alexander Rühle Peter Ernst Huber Department of Radiation Oncology Heidelberg University HospitalIm Neuenheimer Feld 400Heidelberg 69120Germany Department of Molecular Radiation Oncology German Cancer Research CenterIm Neuenheimer Feld 280Heidelberg 69120Germany Heidelberg Institute for Radiation Oncology(HIRO)and National Center for Radiation Oncology(NCRO) Im Neuenheimer Feld 280Heidelberg 69120Germany

Radiotherapy as one of the four pillars of cancer therapy plays a critical role in the multimodal treatment of thoracic *** to significant improvements in overall cancer survival,radiotherapy-induced heart disease(RIHD)has become an increasingly recognized adverse reaction which contributes to major radiationassociated toxicities including non-malignant *** is especially relevant for patients suffering from diseases with excellent prognosis such as breast cancer or Hodgkin’s lymphoma,since RIHD may occur decades after *** studies have enriched our knowledge of many potential mechanisms by which thoracic radiotherapy induces heart *** findings in humans reveal that irradiation might increase the risk of cardiac disease at even lower doses than previously *** preclinical studies have identified non-invasive methods for evaluation of ***,potential options preventing or at least attenuating RIHD have been *** research may enrich our limited knowledge about biological mechanisms of RIHD,identify non-invasive early detection biomarkers and investigate potential treatment options that might attenuate or prevent these unwanted side ***,we present a comprehensive review about the published literature regarding clinical manifestation and pathological alterations in *** mechanisms and treatment options are outlined,and challenges in RIHD treatment are summarized.

关键词： Radiotherapy heart injury thoracic cancer radiation-induced heart injury cancer treatment

Progress in heavy ion cancer therapy at IMP and future development

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Malignancy Spectrum 2024年第2期1卷 91-98页

作者： Qiang Li Xinguo Liu Zhongying Dai Pengbo He Yuanyuan Ma Guosheng Shen Xiaodong Jin Fei Ye Xiaogang Zheng Ting Zhao Hui Zhang Zheng Li bingwen zou Yuehu Pu Weiqiang Chen Institute of Modern Physics Chinese Academy of SciencesLanzhouGansuChina Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences LanzhouGansuChina Gansu Provincial Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine LanzhouGansuChina University of Chinese Academy of Sciences BeijingChina Division of Thoracic Tumor Multimodality Treatment and Department of Radiation Oncology Cancer CenterWest China HospitalSichuan UniversityChengduSichuanChina Medical Equipment Innovation Research Center West China HospitalSichuan UniversityChengduSichuanChina

Basic research on heavy ion cancer therapy such as radiobiology, medicalphysics, and therapeutic technique has been conducted at the Institute ofModern Physics (IMP), Chinese Academy of Sciences since 1995. Based on theachievements acquired in the basic research and the requirements for a heavyion accelerator for radiotherapy purposes, a dedicated heavy ion therapy facilitynamed Heavy Ion Medical Machine (HIMM) was designed at IMP andconstructed in Wuwei, China. The HIMM facility consists of two electroncyclotron resonance ion sources, one cyclotron as the injector and onesynchrotron as the main accelerator, and four different treatment roomsequipped with passive or active beam delivery systems, and accelerates carbonions up to 400 MeV/u. After the performance inspection of HIMM organized bythe National Medical Device Inspection Center, preclinical tests like cell andanimal radiobiological experiments and dosimetric verification using anthropomorphicphantoms for elucidating the biophysical properties of the carbon ionbeams provided by HIMM were carried out. According to the Chinese medicaldevice regulations, a clinical trial in which 46 tumor patients were recruited andtwo hospitals participated was conducted in the HIMM facility, aiming atevaluating the treatment safety and short-term efficacy of the medical *** success of the clinical trial helped the HIMM facility be authorized by theChinese government as a class III medical device. In this paper, all the aspectsmentioned above are introduced and discussed, and implications for futureimprovements are also given.

关键词： heavy ion cancer therapy clinical trial performance inspection dosimetric verification medical device

全脑低剂量放疗联合ICI及鞘内化疗治疗非小细胞肺癌脑膜转移的安全性与疗效分析

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中国肿瘤临床 2024年第18期51卷 943-949页

作者：向丽莎张轩薇余敏修为刚邹炳文徐泳刘咏梅周麟薛建新卢铀四川大学华西医院肿瘤中心胸部肿瘤病房及肿瘤放射治疗科成都市610041

目的:探索经全脑低剂量放疗(whole-brain low-dose radiotherapy,WB-LDRT)联合程序性死亡受体-1(programmed cell death protein-1,PD-1)抑制剂信迪利单抗及培美曲塞鞘内化疗(intrathecal pemetrexed,IP)的联合治疗方案治疗难治性非小细胞肺癌(non-small cell lung cancer,NSCLC)伴脑膜转移(leptomeningeal metastases,LM)的疗效和安全性。方法:回顾性分析2022年12月至2024年5月于四川大学华西医院收治的8例NSCLC伴LM患者的临床资料。患者男性4例,女性4例,年龄34~58岁,中位年龄49岁。所有患者均接受WB-LDRT联合免疫检查点抑制剂(immune checkpoint inhibitor,ICI)及鞘内化疗方案治疗,根据神经肿瘤评估标准(RANO)进行疗效评价;以及卡氏体力状态评分标准(KPS)体力状态评分,评估患者生命质量;根据常见不良事件评价标准(CTCAE)5.0版评估不良反应。生存分析采用Kaplan-Meier法;通过单细胞测序分析患者治疗前后脑脊液细胞亚群分类占比,并行细胞基因表达差异分析。结果:接受治疗8例患者RANO标准评估最佳临床疗效,5例(62.5%)评价为好转,3例(37.5%)评价为稳定;8例患者治疗前中位KPS评分为30(20~50)分,治疗后中位KPS评分明显提高,为60(40~90)分(P=0.000 9);8例患者观察到神经症状的缓解率为100%(8/8);中位神经系统无进展生存期(neurological progression-free survival,NPFS)为12个月。P1患者脑脊液单细胞测序结果提示,WB-LDRT治疗后患者脑脊液细胞分群中T细胞比率较治疗前明显上升(治疗前vs.治疗后:6.08%vs. 68.87%),肿瘤细胞比率明显下降(治疗前vs.治疗后:12.92%vs.0.60%);WB-LDRT治疗后脑脊液T细胞显著上调基因包括CCL5及CXCL13等。结论:采用WB-LDRT联合方案(WBLDRT+IP+ICI)治疗NSCLC伴LM可明显缓解患者神经症状、改善患者生存质量及延长颅内无进展生存生存时间,是一种安全有效的治疗措施。

关键词：非小细胞肺癌脑膜转移全脑低剂量放疗免疫治疗鞘内注射治疗培美曲塞

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59例骶尾部脊索瘤术后放疗后的生存分析

肿瘤预防与治疗 2019年第1期32卷 38-42页

作者：路顺邹炳文彭新皓张菡奕郎锦义四川省肿瘤医院.研究所四川省癌症防治中心电子科技大学医学院四川大学华西医院胸部肿瘤科成都614041

目的:明确骶尾部脊索瘤患者是否能从术后的辅助放疗中获益,并且探索恰当的术后放疗模式。方法:回顾性纳入59例无远处转移且病理诊断明确为骶尾部脊索瘤的患者,分析其术后辅助放疗的生存情况。患者分为3组:22例为单纯手术切除组,24例为... 详细信息

目的:明确骶尾部脊索瘤患者是否能从术后的辅助放疗中获益,并且探索恰当的术后放疗模式。方法:回顾性纳入59例无远处转移且病理诊断明确为骶尾部脊索瘤的患者,分析其术后辅助放疗的生存情况。患者分为3组:22例为单纯手术切除组,24例为手术联合术后图像引导下调强放疗(IG-IMRT)治疗组,13例为手术联合伽马刀(GKS)治疗组。结果:所有患者的5年生存率及5年无复发生存率分别为80.1%和44.5%;单纯手术组、IG-IMRT组及GKS组5年生存率分别为90.9%、87.5%及59.3%,5年无复发生存率分别为29.8%、70.9%和35.0%;术后辅助放疗组对比单纯手术组的5年无复发生存率差异具有统计学意义(P=0.029),IG-IMRT组的5年无复发生存率优于GKS组(P=0.023)。结论:术后辅助放疗有助于提升脊索瘤术后患者的5年无复发生存率,且术后辅助IG-IMRT可能是更为恰当的术后放疗模式。

关键词：骶尾部脊索瘤外科手术辅助放疗 IG-IMRT GKS

厄洛替尼挽救治疗吉非替尼治疗失败的晚期非小细胞肺癌疗效观察

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重庆医学 2011年第20期40卷 1997-1999,2002页

作者：罗大先龙建林丘金凤余敏邹炳文周麟卢铀黄媚娟四川大学华西医院肿瘤中心胸部肿瘤科成都610041

目的评价厄洛替尼作为挽救方案治疗吉非替尼治疗失败的晚期非小细胞肺癌的疗效及不良反应。方法回顾性分析2005年12月至2009年11月吉非替尼治疗进展后接受厄洛替尼治疗的晚期非小细胞肺癌患者。观察的主要指标为:客观有效率(RR)、疾病... 详细信息

目的评价厄洛替尼作为挽救方案治疗吉非替尼治疗失败的晚期非小细胞肺癌的疗效及不良反应。方法回顾性分析2005年12月至2009年11月吉非替尼治疗进展后接受厄洛替尼治疗的晚期非小细胞肺癌患者。观察的主要指标为:客观有效率(RR)、疾病控制率(DCR)、疾病无进展生存时间(PFS)、总生存时间(OS)及不良反应。结果随访至2010年6月,共有22例患者符合入组条件。22例患者均可接受疗效及生存评价,其中部分缓解(PR)2例,稳定(SD)12例,进展(PD)8例,RR为9.1%,DCR为63.6%,中位为PFS 3.0个月,OS为5.5个月。4例患者检测了表皮生长因子受体(EGFR)突变,2例有突变,2例无突变,全部患者均得到疾病控制。1例男性吸烟腺癌合并颅内转移患者原发无效给予厄洛替尼治疗后颅内病灶达到CR。亚组分析显示:吉非替尼治疗疗效SD者DCR显著提高(90%vs 58.3%,P=0.031),其RR、PFS及OS分别为20%、3.0个月及5.5个月。Ⅲ/Ⅳ度不良反应主要是皮疹1/22(4.5%)、肝功能损害1/22(4.5%)及肺间质纤维化1/22(4.5%)。结论吉非替尼治疗失败后的晚期非小细胞肺癌给予厄洛替尼挽救治疗具有较好的临床获益率,其中吉非替尼治疗疗效SD患者显著提高疾病控制率。

关键词：癌非小细胞肺厄洛替尼吉非替尼

基于光学表面成像与锥形束CT结合的综合引导模式在头颈部肿瘤精确放疗中的研究

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中国辐射卫生 2019年第3期28卷 346-350页

作者：叶程伟周继丹商强周兆明柏森钟仁明邹炳文四川大学华西医院肿瘤中心放疗科四川成都610041 广东三九脑科医院四川大学华西医院肿瘤中心胸部肿瘤科

目的探讨光学表面成像(OSI)Catalyst^TM系统与锥形束CT(CBCT)相结合用于引导头颈部肿瘤精确放疗的临床价值。方法82名患者均来自四川大学华西医院2015年2月至2018年1月收治的需要进行头颈部肿瘤放射治疗的患者,其中45名患者使用OSI-CBC... 详细信息

目的探讨光学表面成像(OSI)Catalyst^TM系统与锥形束CT(CBCT)相结合用于引导头颈部肿瘤精确放疗的临床价值。方法82名患者均来自四川大学华西医院2015年2月至2018年1月收治的需要进行头颈部肿瘤放射治疗的患者,其中45名患者使用OSI-CBCT综合引导放射治疗,37名患者CBCT独立引导治疗。每组患者在治疗疗程中均获得208次有效分次治疗;对综合引导治疗组与独立引导治疗组CBCT所得到的摆位误差数据进行统计学分析。结果独立引导组CBCT扫描得出的分次间摆位误差平移方向x、y、z和旋转方向rx、ry、rz的结果(均值±标准差)分别为(0.19±1.01)mm、(0.29±1.36)mm、(-0.05±1.23)mm,(-0.05±0.65)°、(0.18±0.83)°、(-0.12±0.59)°;综合引导组OSI-CBCT得出的分次间摆位误差的结果分别为(0±1)mm、(0.01±0.98)mm、(-0.4±1.08)mm,(-0.03±0.72)°、(-0.19±0.82)°、(-0.37±0.85)°。两系统的相关性系数分别为:0.17、0.07、0.03、0.1、-0.06、0.01。两系统进行配对样本t检验,结果分别为(0.19±1.3)mm,P0.05;(0.37±1.2)°,P<0.05、(0.25±1.03)°,P<0.05。结论OSI-CBCT系统综合引导模式在保证放疗精确性的同时可以减少CBCT扫描次数,能有效降低CBCT带来的额外辐射量,在头颈部肿瘤放疗中优于传统的单一的CBCT引导模式。

关键词： OSI OSI-CBCT综合引导模式锥形束CT(CBCT) 头颈部肿瘤放射治疗摆位误差