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放射物理学及分子放射生物学在临床放疗实践中的应用和未来发展

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癌症 2008年第8期27卷 885-893页

作者： Bin S Teh Arnold Paulino E Brian Butler Department of radiation oncology The Methodist HospitalThe Methodist Hospital Research InstituteHoustonTexas77030USA

最近几年,放射物理学和分子放射生物学的进步促进了放射肿瘤学的显著发展。目前,我们从常规的二维放疗到三维适形放疗,已进入了调强放疗(intensity-modulated radiotherapy,IMRT)和影像引导放疗(image-guided radiotherapy,IGRT)的时代... 详细信息

最近几年,放射物理学和分子放射生物学的进步促进了放射肿瘤学的显著发展。目前,我们从常规的二维放疗到三维适形放疗,已进入了调强放疗(intensity-modulated radiotherapy,IMRT)和影像引导放疗(image-guided radiotherapy,IGRT)的时代。IMRT/IGRT可对肿瘤组织进行适形治疗,对正常组织适形地避免照射,从而改善肿瘤控制并减少治疗相关的放射损伤。目前无框架立体定向放射手术(stereotactic radiosurgery,SRS)和立体定向体部放疗(stereotactic body radiotherapy,SBRT)已进入临床应用,这为放射肿瘤临床提供了更多的治疗选择。随着影像引导技术的进步,近距离放疗得到了发展,尤其是应用于早期前列腺癌,获得了非常满意的长期疗效。带电粒子治疗,包括质子疗法是新开发的充满前景的领域。放疗与传统化疗、激素疗法、新的靶向治疗和基因疗法联合使用为克服放疗抗拒、改善放疗指数提供了更好的局部-区域和全身癌症控制效果。最近进行的一项关于头颈部癌的随机临床试验表明,与单纯放疗相比,放疗联合靶向治疗可以提高患者生存率,而在功能或分子影像学方面取得的进步为提高人们对肿瘤靶区的认识提供了新的机会(例如乏氧区),并可进行对应放射剂量的调强治疗。在放疗中整合PET/CT可在治疗计划测定中有助于进行靶区勾画和对放疗反应的评估。放射抗拒相关的肿瘤干细胞、基因表达图谱分析以及毫微秒技术也是新进展的领域,随着个体化用药的发展,正在作进一步研究。

关键词：肿瘤/放射疗法放射物理学分子放射生物学

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 xenobiotics.These effects are mainly achieved by the driving effect of NAD^(+)on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions.Besides,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 disorder.In 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

Advances of stereotactic body radiotherapy in pancreatic cancer

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Chinese Journal of Cancer Research 2015年第4期27卷 349-357页

作者： Qichun Wei Wei Yu Lauren M.Rosati Joseph M.Herman Department of radiation oncology the Second Affiliated Hospital Zhejiang University School of Medicine Department of radiation oncology & molecular radiation Sciences Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine

Pancreatic cancer（PCA） is one of the most aggressive tumors with few effective treatment modalities. It is the 4th and 7th leading cause of cancer death in the United States and China, respectively. At the time of diagnosis, only 20% of cases present with a resectable tumor, and about 40% with a locally advanced tumor that is considered unresectable. Even resected patients still have a poor prognosis, with an incidence of local recurrence ranging from 20% to 60%. It is also reported that up to 30% of PCA patients die from locally obstructive disease with few or no distant metastases. These findings have highlighted the importance of local radiation therapy in the treatment of PCA. As the role of conventional chemoradiotherapy remains controversial, the dawn of the pancreas stereotactic body radiation therapy（SBRT） era represents a potential paradigm shift in the management of PCA. SBRT delivers a higher biological effective dose to the tumor with sharp dose escalation in a shorter treatment time course. Pancreas SBRT is a novel therapeutic option to achieve local tumor control with minimal toxicity. Herein, we review the advancement of SBRT for PCA patients with different stages of pancreatic adenocarcinoma.

关键词： Stereotactic body radiation therapy（SBRT） pancreatic cancer（PCA）

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 cancers.Due 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 death.This 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 radiotherapy.Preclinical studies have enriched our knowledge of many potential mechanisms by which thoracic radiotherapy induces heart injury.Epidemiological findings in humans reveal that irradiation might increase the risk of cardiac disease at even lower doses than previously assumed.Recent preclinical studies have identified non-invasive methods for evaluation of RIHD.Furthermore,potential options preventing or at least attenuating RIHD have been developed.Ongoing 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 effects.Here,we present a comprehensive review about the published literature regarding clinical manifestation and pathological alterations in RIHD.Biological 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

Selectively enhancing radiosensitivity of cancer cells via in situ enzyme-instructed peptide self-assembly

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2374-2383页

作者： Yang Gao Jie Gao Ganen Mu Yumin Zhang Fan Huang Wenxue Zhang Chunhua Ren Cuihong Yang Jianfeng Liu Tianjin Key Laboratory of radiation Medicine and molecular Nuclear Medicine Institute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China radiation oncology Department Tianjin Medical University General HospitalTianjin 300052China

The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity.For the first time,we used the in situ enzyme-instructed self-assembly(EISA)of a peptide derivative(Nap-GDFDFpYSV)to selectively enhance the sensitivity of cancer cells with high alkaline phosphatase(ALP)expression to ionizing radiation(IR).Compared with the in vitro pre-assembled control formed by the same molecule,assemblies formed by in situ EISA in cells greatly sensitized the ALPhigh-expressing cancer cells to y-rays,with a remarkable sensitizer enhancement ratio.Our results indicated that the enhancement was a result of fixing DNA damage,arresting cell cycles and inducing cell apoptosis.Interestingly,in vitro pre-formed assemblies mainly localized in the lysosomes after incubating with cells,while the assemblies formed via in situ EISA scattered in the cell cytosol.The accumulation of these molecules in cells could not be inhibited by endocytosis inhibitors.We believed that this molecule entered cancer cells by diffusion and then in situ self-assembled to form nanofibers under the catalysis of endogenous ALP.This study provides a successful example to utilize intracellular in situ EISA of small molecules to develop selective tumor radiosensitizers.

关键词： In situ enzyme-instructed self-assembly(EISA) Pre-assembly Alkaline phosphatase(ALP) Peptide Cancer radiotherapy Nanofiber Histone deacetylases inhibitor(HDACI) Radiosensitizer

Identification of Factors Influencing Radiotherapy Errors during radiation Treatments Using Quality Management Tools

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肿瘤预防与治疗 2022年第1期35卷 7-13页

作者： Li Lintao Lucia Clara Orlandini Wang Xianliang Fan Ming Lu Shun Kang Shengwei Zhang Dekang Heng Li Department of radiation oncology Sichuan Cancer HospitalChengdu 610041China Department of radiation Oncol ogy and molecular radiation Sciences Johns Hopkins University School of MedicineBaltimoreMD 21205USA

Objective:To investigate factors that may cause radiotherapy errors during radiation treatments using quality management tools.Methods:The Delphi method was used to sort out the factors that cause radiotherapy errors which were then clasified by the Kaiser model.Results:In the first round of brainstorming,33 types of influencing factors were put forward,which were further reduced to 19 through the Delphi method.The recruited factors were,then,divided into four types by the Kaiser model,radiotherapyspecific factors with the mean weight of 49.49%,patient-related factors with the mean weight of 42.27%,therapist-related factors with the mean weight of 35.64% and hardware-related factors with the mean weight of 19.72%.Conclusion:Delphi plus Kaiser may be a promising method for predicting factors that may cause radiotherapy errors,which is worthy of further research.

关键词： Radiotherapy errors Delphi method Kaiser model Radiotherapy

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血液中羟基化缓激肽作为肿瘤厌氧指标的研究

Science Bulletin 2020年第18期65卷 1570-1579,M0004页

作者：刘洋谷雅君 Serina Ng 邓载安 Christopher J.Lyon Eugene J.Koay 宁波 Matthew H.Katz Paul J.Chiao 范佳韩海勇 Daniel Von Hoff 胡晔 Department of Biochemistry and molecular Biology Tulane University School of MedicineNew Orleans.LA 70112USA Department of Nanomedicine Houston Methodist Research InstituteHoustonTX 77030USA molecular Medicine Division Translational Genomics Research InstitutePhoenixAZ 85004USA Department of radiation oncology Division of Radiation OncologyThe University of Texas M.D.Anderson Cancer CenterHoustonTX 77030USA Department of Surgical oncology Division of SurgeryThe University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of molecular and Cellular oncology Division of Basic SciencesThe University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

组织缺氧在消化系统、呼吸系统、肾脏疾病和癌症等多种疾病的发生发展中起到关键作用.然而,由于缺乏快速、准确和非侵入性的检测方法,评估组织缺氧情况和预测患者的预后结果仍然具有非常大的挑战性.本文假设血液中Hyp-BK/BK比率可以作... 详细信息

组织缺氧在消化系统、呼吸系统、肾脏疾病和癌症等多种疾病的发生发展中起到关键作用.然而,由于缺乏快速、准确和非侵入性的检测方法,评估组织缺氧情况和预测患者的预后结果仍然具有非常大的挑战性.本文假设血液中Hyp-BK/BK比率可以作为缺氧检测的标志物,以胰腺癌作为研究模型,通过监测Hyp-BK/BK比率可以预测组织缺氧水平以及抗肿瘤治疗的预后情况.研究表明,缺氧条件下肿瘤组织中高表达的P4HA1和治疗前患者血液样本中Hyp-BK/BK比率升高有关,并且两者都与患者预后不良相关.这些结果有力地表明血液中Hyp-BK/BK比率可以作为非侵入性的组织缺氧标志物,对胰腺癌的预后和治疗效果进行预测.

关键词： HIF-1α Hypoxia Circulating indicator Hydroxyprolyl bradykinin P4HA1

Targets and molecular mechanisms of triptolide in cancer therapy

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Chinese Journal of Cancer Research 2014年第5期26卷 622-626页

作者： Cuicui Meng Hongcheng Zhu Hongmei Song Zhongming Wang Guanhong Huang Defan Li Zhaoming Ma Jianhua Ma Qin Qin Xinchen Sun Jianxin Ma Bengbu Medical College Department of radiation oncology The First Affiliated Hospital of Nanjing Medical University Department of radiation oncology Lianyungang No.2 People’s Hospital

Triptolide（TPL/TL） is a natural drug with novel anticancer effects. Preclinical studies indicated that TPL inhibits cell proliferation, induces cell apoptosis, inhibits tumor metastasis and enhances the effect of other therapeutic methods in various cancer cell lines. Multiple molecules and signaling pathways, such as caspases, heat-shock proteins, NF-κB, and deoxyribonucleic acid（DNA） repair-associated factors, are associated with the anti-cancer effect. TPL also improves chemoradiosensitivity in cancer therapy. Phase I trials indicate the potential clinical value of TPL use. However, further trials with larger sample sizes are needed to confirm these results.

关键词： Triptolide（TPL/TL） neoplasms antineoplastic cancer

High-dose radiation associated with improved survival in IDH-wildtype lowgrade glioma

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Chinese Neurosurgical Journal 2021年第2期7卷 126-130页

作者： Shuai Liu Yanwei Liu Guanzhang Li Jin Feng Li Chen Xiaoguang Qiu Department of radiation oncology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijing 100070China

Background:As molecular advances have deepened the knowledge on low-grade glioma(LGG),we investigated the effect of higher radiation dose on the survival of IDH-wildtype(IDHwt)LGG.Methods:In the current study,52 IDHwt LGG patients who received radiotherapy were enrolled from the Chinese Glioma Genome Atlas dataset.radiation doses>54 Gy were defined as high-dose,whereas doses≤54 Gy were defined as low-dose.We performed univariate and multivariate survival analyses to examine the prognostic role of high-dose radiotherapy.Results:In total,the radiation dose ranged from 48.6 Gy to 61.2 Gy,with a median of 55.8 Gy,and 31 patients were grouped into high-dose radiation.Univariate survival analysis indicated that high-dose radiotherapy(p=0.015),tumors located in the frontal lobe(p=0.009),and pathology of astrocytoma(p=0.037)were significantly prognostic factors for overall survival.In multivariate survival analysis,high-dose radiotherapy(p=0.028)and tumors located in the frontal lobe(p=0.016)were independently associated with better overall survival.Conclusions:In conclusion,high-dose radiotherapy independently improved the survival of IDHwt LGG.This can guide treatments for glioma with known molecular characteristics.

关键词： radiation dose IDH-wildtype Low-grade glioma Survival