FLASH放射生物学机制及治疗计划研究进展

吴迅; 刘锐锋; 张秋宁; 王小虎

doi:10.11889/j.1000-3436.2022-0074

您当前的位置：

首页 >

文章列表页 >

FLASH放射生物学机制及治疗计划研究进展

综述 | 更新时间：2023-04-20

- FLASH放射生物学机制及治疗计划研究进展
- Radiobiology and treatment plan progress of FLASH radiotherapy
- 辐射研究与辐射工艺学报 2023年41卷第2期页码：20101
- 作者机构：
  
  1.中国科学院近代物理研究所兰州 730000
  2.兰州大学第一临床医学院兰州 730000
  3.兰州重离子医院兰州 730000
  4.中国科学院大学北京 100049
- 作者简介：
  
  吴迅，男，1991年8月出生，2019年硕士毕业于川北医学院，现为兰州大学博士研究生
  王小虎，教授，博士生导师，主任医师，E-mail: xhwang@impcas.ac.cn
- 基金信息：
  
  甘肃省科技厅重点研发计划项目(20YF8FA116);兰州市人才创新创业项目(2020-RC-113);兰州科近泰基新技术有限责任公司研发项目(1100090020)
- DOI：10.11889/j.1000-3436.2022-0074
  中图分类号：
扫描看全文
吴迅, 刘锐锋, 张秋宁, 等. FLASH放射生物学机制及治疗计划研究进展[J]. 辐射研究与辐射工艺学报, 2023,41(2):020101.

WU Xun, LIU Ruifeng, ZHANG Qiuning, et al. Radiobiology and treatment plan progress of FLASH radiotherapy[J]. Journal of Radiation Research and Radiation Processing, 2023,41(2):020101.
吴迅, 刘锐锋, 张秋宁, 等. FLASH放射生物学机制及治疗计划研究进展[J]. 辐射研究与辐射工艺学报, 2023,41(2):020101. DOI： 10.11889/j.1000-3436.2022-0074.

WU Xun, LIU Ruifeng, ZHANG Qiuning, et al. Radiobiology and treatment plan progress of FLASH radiotherapy[J]. Journal of Radiation Research and Radiation Processing, 2023,41(2):020101. DOI： 10.11889/j.1000-3436.2022-0074.

摘要

近年来，一项被称为FLASH放疗的新技术具有将辐射的治疗增益比推向一个新高度的潜力。FLASH放疗是一种以超高剂量率照射为主要特征的放疗技术，能显著减轻辐射对正常组织的损伤，同时保留辐射对肿瘤的杀伤能力。一方面，作为一种新兴的放疗技术，FLASH放疗的生物学机制尚未被阐明，这阻碍了其临床转化；另一方面，超高剂量率照射技术的临床应用也存在许多技术困难。本综述通过归纳FLASH放射生物学机制的研究进展，总结FLASH放疗治疗计划所面临的困难及可能的解决方案，旨在为后续FLASH放疗的临床转化提供参考。

Abstract

FLASH radiotherapy is a novel method that has the potential to improve the therapeutic gain ratio to a new level. FLASH radiotherapy technology is mainly characterized by irradiation at ultra-high dose rate, which can reduce radiation-induced injury to normal tissues during radiotherapy, while maintaining the ability of radiation damage to tumors. On the one hand, as a new radiotherapy technology, the radiobiological mechanisms of FLASH are unclear, which hinders its clinical transformation. On the other hand, there are many technical difficulties in the clinical application of ultra-high dose rate irradiation technology. This paper summarizes the research progress of radiobiological mechanisms underlying FLASH radiotherapy, as well as the challenges and possible solutions associated with FLASH radiotherapy treatment plans, to provide a reference for clinical translation of subsequent FLASH radiotherapy.

关键词

FLASH超高剂量率放疗放射生物学治疗计划

Keywords

FLASHUltra-high dose rateRadiotherapyRadiobiologyTreatment planning

references

Favaudon V, Caplier L, Monceau V, et al. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice[J]. Science Translational Medicine, 2014, 6(245): 245ra293. DOI: 10.1126/scitranslmed.3008973http://dx.doi.org/10.1126/scitranslmed.3008973.

Kacem H, Almeida A, Cherbuin N, et al. Understanding the FLASH effect to unravel the potential of ultra-high dose rate irradiation[J]. International Journal of Radiation Biology, 2022, 98(3): 506-516. DOI: 10.1080/09553002. 2021.2004328http://dx.doi.org/10.1080/09553002.2021.2004328.

Schüler E, Acharya M, Montay-Gruel P, et al. Ultra-high dose rate electron beams and the FLASH effect: from preclinical evidence to a new radiotherapy paradigm[J]. Medical Physics, 2022, 49(3): 2082-2095. DOI: 10.1002/mp.15442http://dx.doi.org/10.1002/mp.15442.

Tinganelli W, Weber U, Puspitasari A, et al. FLASH with carbon ions: Tumor control, normal tissue sparing, and distal metastasis in a mouse osteosarcoma model[J]. Radiotherapy and Oncology, 2022, 175: 185-190. DOI: 10.1016/j.radonc.2022.05.003http://dx.doi.org/10.1016/j.radonc.2022.05.003.

Vozenin M C, De Fornel P, Petersson K, et al. The advantage of FLASH radiotherapy confirmed in mini-pig and cat-cancer patients[J]. Clinical Cancer Research, 2019, 25(1): 35-42. DOI: 10.1158/1078-0432.CCR-17-3375http://dx.doi.org/10.1158/1078-0432.CCR-17-3375.

Konradsson E, Arendt M L, Bastholm Jensen K, et al. Establishment and initial experience of clinical FLASH radiotherapy in canine cancer patients[J]. Frontiers in Oncology, 2021, 11: 658004. DOI: 10.3389/fonc.2021. 658004http://dx.doi.org/10.3389/fonc.2021.658004.

Bourhis J, Sozzi W J, Jorge P G, et al. Treatment of a first patient with FLASH-radiotherapy[J]. Radiotherapy and Oncology, 2019, 139: 18-22. DOI: 10.1016/j.radonc. 2019.06.019http://dx.doi.org/10.1016/j.radonc.2019.06.019.

Berry R J, Hall E J, Forster D W, et al. Survival of mammalian cells exposed to x rays at ultra-high dose-rates[J]. The British Journal of Radiology, 1969, 42(494): 102-107. DOI: 10.1259/0007-1285-42-494-102http://dx.doi.org/10.1259/0007-1285-42-494-102.

Phillips T L, Worsnop B R. Ultra-high dose-rate effects in radiosensitive bacteria[J]. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine, 1969, 14(6): 573-575. DOI: 10. 1080/09553006914551761http://dx.doi.org/10.1080/09553006914551761.

Epp E R, Weiss H, Santomasso A. The oxygen effect in bacterial cells irradiated with high-intensity pulsed electrons[J]. Radiation Research, 1968, 34(2): 320-325. 10.2307/3572557http://dx.doi.org/10.2307/3572557

Zakaria A M, Colangelo N W, Meesungnoen J, et al. Transient hypoxia in water irradiated by swift carbon ions at ultra-high dose rates: implication for FLASH carbon-ion therapy[J]. Canadian Journal of Chemistry, 2021, 99(10): 842-849. DOI: 10.1139/cjc-2021-0110http://dx.doi.org/10.1139/cjc-2021-0110.

Cao X, Zhang R X, Esipova T V, et al. Quantification of oxygen depletion during FLASH irradiation in vitro and in vivo[J]. International Journal of Radiation Oncology, Biology, Physics, 2021, 111(1): 240-248. DOI: 10.1016/j.ijrobp.2021.03.056http://dx.doi.org/10.1016/j.ijrobp.2021.03.056.

Jansen J, Knoll J, Beyreuther E, et al. Does FLASH deplete oxygen? Experimental evaluation for photons, protons, and carbon ions[J]. Medical Physics, 2021, 48(7): 3982-3990. DOI: 10.1002/mp.14917http://dx.doi.org/10.1002/mp.14917.

Lai Y F, Jia X, Chi Y J. Modeling the effect of oxygen on the chemical stage of water radiolysis using GPU-based microscopic Monte Carlo simulations, with an application in FLASH radiotherapy[J]. Physics in Medicine and Biology, 2021, 66(2): 025004. DOI: 10. 1088/1361-6560/abc93bhttp://dx.doi.org/10.1088/1361-6560/abc93b.

Rothwell B C, Kirkby N F, Merchant M J, et al. Determining the parameter space for effective oxygen depletion for FLASH radiation therapy[J]. Physics in Medicine and Biology, 2021, 66(5): 055020. DOI: 10. 1088/1361-6560/abe2eahttp://dx.doi.org/10.1088/1361-6560/abe2ea.

Okoro C M, Schüler E, Taniguchi C M. The therapeutic potential of FLASH-RT for pancreatic cancer[J]. Cancers, 2022, 14(5): 1167. DOI: 10.3390/cancers14051167http://dx.doi.org/10.3390/cancers14051167.

Boscolo D, Scifoni E, Durante M, et al. May oxygen depletion explain the FLASH effect? A chemical track structure analysis[J]. Radiotherapy and Oncology, 2021, 162: 68-75. DOI: 10.1016/j.radonc.2021.06.031http://dx.doi.org/10.1016/j.radonc.2021.06.031.

Wilson J D, Hammond E M, Higgins G S, et al. Ultra-high dose rate (FLASH) radiotherapy: silver bullet or fool's gold?[J]. Frontiers in Oncology, 2020, 9: 1563. DOI: 10.3389/fonc.2019.01563http://dx.doi.org/10.3389/fonc.2019.01563.

Petersson K, Adrian G, Butterworth K, et al. A quantitative analysis of the role of oxygen tension in FLASH radiation therapy[J]. International Journal of Radiation Oncology, Biology, Physics, 2020, 107(3): 539-547. DOI: 10.1016/j.ijrobp.2020.02.634http://dx.doi.org/10.1016/j.ijrobp.2020.02.634.

Vozenin M C, Hendry J H, Limoli C L. Biological benefits of ultra-high dose rate FLASH radiotherapy: sleeping beauty awoken[J]. Clinical Oncology, 2019, 31(7): 407-415. DOI: 10.1016/j.clon.2019.04.001http://dx.doi.org/10.1016/j.clon.2019.04.001.

Hu A K, Qiu R, Wu Z, et al. A computational model for oxygen depletion hypothesis in FLASH effect[J]. Radiation Research, 2022, 197(2): 175-183. DOI: 10. 1667/RADE-20-00260.1http://dx.doi.org/10.1667/RADE-20-00260.1.

Hornsey S, Bewley D K. Hypoxia in mouse intestine induced by electron irradiation at high dose-rates[J]. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine, 1971, 19(5): 479-483. DOI: 10.1080/09553007114550611http://dx.doi.org/10.1080/09553007114550611.

Spitz D R, Buettner G R, Petronek M S, et al. An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses[J]. Radiotherapy and Oncology, 2019, 139: 23-27. DOI: 10. 1016/j.radonc.2019.03.028http://dx.doi.org/10.1016/j.radonc.2019.03.028.

Wardman P. Radiotherapy using high-intensity pulsed radiation beams (FLASH): a radiation-chemical perspective[J]. Radiation Research, 2020, 194(6): 607-617. DOI: 10.1667/RADE-19-00016http://dx.doi.org/10.1667/RADE-19-00016.

Friedl A A, Prise K M, Butterworth K T, et al. Radiobiology of the FLASH effect[J]. Medical Physics, 2022, 49(3): 1993-2013. DOI: 10.1002/mp.15184http://dx.doi.org/10.1002/mp.15184.

Labarbe R, Hotoiu L, Barbier J, et al. A physicochemical model of reaction kinetics supports peroxyl radical recombination as the main determinant of the FLASH effect[J]. Radiotherapy and Oncology, 2020, 153: 303-310. DOI: 10.1016/j.radonc.2020.06.001http://dx.doi.org/10.1016/j.radonc.2020.06.001.

Zhu H Y, Xie D H, Yang Y W, et al. Radioprotective effect of X-ray abdominal FLASH irradiation: adaptation to oxidative damage and inflammatory response may be benefiting factors[J]. Medical Physics, 2022, 49(7): 4812-4822. DOI: 10.1002/mp.15680http://dx.doi.org/10.1002/mp.15680.

Favaudon V, Labarbe R, Limoli C L. Model studies of the role of oxygen in the FLASH effect[J]. Medical Physics, 2022, 49(3): 2068-2081. DOI: 10.1002/mp.15129http://dx.doi.org/10.1002/mp.15129.

Blain G, Vandenborre J, Villoing D, et al. Proton irradiations at ultra-high dose rate vs. conventional dose rate: strong impact on hydrogen peroxide yield[J]. Radiation Research, 2022, 198(3): 318-324. DOI: 10. 1667/RADE-22-00021.1http://dx.doi.org/10.1667/RADE-22-00021.1.

Hu A K, Qiu R, Wu Z, et al. CPU-GPU coupling independent reaction times method in NASIC and application in water radiolysis by FLASH irradiation[J]. Biomedical Physics & Engineering Express, 2022, 8(2): 025015. DOI: 10.1088/2057-1976/ac52d9http://dx.doi.org/10.1088/2057-1976/ac52d9.

Kim Y E, Gwak S H, Hong B J, et al. Effects of ultra-high doserate FLASH irradiation on the tumor microenvironment in lewis lung carcinoma: role of myosin light chain[J]. International Journal of Radiation Oncology, Biology, Physics,, 2021, 109(5): 1440-1453. DOI: 10.1016/j.ijrobp.2020.11.012http://dx.doi.org/10.1016/j.ijrobp.2020.11.012.

Prempree T, Michelsen A, Merz T. The repair time of chromosome breaks induced by pulsed X-rays on ultra-high dose-rate[J]. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine, 1969, 15(6): 571-574. DOI: 10.1080/09553006914550871http://dx.doi.org/10.1080/09553006914550871.

Michaels H B, Epp E R, Ling C C, et al. Oxygen sensitization of CHO cells at ultrahigh dose rates: prelude to oxygen diffusion studies[J]. Radiation Research, 1978, 76(3): 510-521. 10.2307/3574800http://dx.doi.org/10.2307/3574800

Schulz R J, Nath R, Testa J R. The effects of ultra-high dose rates on survival and sublethal repair in Chinese-hamster cells[J]. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine, 1978, 33(1): 81-88. DOI: 10.1080/09553007714551521http://dx.doi.org/10.1080/09553007714551521.

Ohsawa D, Hiroyama Y, Kobayashi A, et al. DNA strand break induction of aqueous plasmid DNA exposed to 30 MeV protons at ultra-high dose rate[J]. Journal of Radiation Research, 2022, 63(2): 255-260. DOI: 10.1093/jrr/rrab114http://dx.doi.org/10.1093/jrr/rrab114.

Perstin A, Poirier Y, Sawant A, et al. Quantifying the DNA-damaging effects of FLASH irradiation with plasmid DNA[J]. International Journal of Radiation Oncology, Biology, Physics, 2022, 113(2): 437-447. DOI: 10.1016/j.ijrobp.2022.01.049http://dx.doi.org/10.1016/j.ijrobp.2022.01.049.

Fouillade C, Curras-Alonso S, Giuranno L, et al. FLASH irradiation spares lung progenitor cells and limits the incidence of radio-induced senescence[J]. Clinical Cancer Research, 2020, 26(6): 1497-1506. DOI: 10.1158/1078-0432.CCR-19-1440http://dx.doi.org/10.1158/1078-0432.CCR-19-1440.

Adrian G, Konradsson E, Beyer S, et al. Cancer cells can exhibit a sparing FLASH effect at low doses under normoxic in vitro- conditions[J]. Frontiers in Oncology, 2021, 11: 686142. DOI: 10.3389/fonc.2021.686142http://dx.doi.org/10.3389/fonc.2021.686142.

Shi X L, Yang Y W, Zhang W, et al. FLASH X-ray spares intestinal crypts from pyroptosis initiated by cGAS-STING activation upon radioimmunotherapy[J]. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119(43): e2208506119. DOI: 10.1073/pnas.2208506119http://dx.doi.org/10.1073/pnas.2208506119.

Buonanno M, Grilj V, Brenner D J. Biological effects in normal cells exposed to FLASH dose rate protons[J]. Radiotherapy and Oncology, 2019, 139: 51-55. DOI: 10. 1016/j.radonc.2019.02.009http://dx.doi.org/10.1016/j.radonc.2019.02.009.

Cooper C R, Jones D, Jones G D, et al. FLASH irradiation induces lower levels of DNA damage ex vivo, an effect modulated by oxygen tension, dose, and dose rate[J]. The British Journal of Radiology, 2022, 95(1133): 20211150. DOI: 10.1259/bjr.20211150http://dx.doi.org/10.1259/bjr.20211150.

Jin J Y, Gu A, Wang W, et al. Ultra-high dose rate effect on circulating immune cells: a potential mechanism for FLASH effect?[J]. Radiotherapy and Oncology, 2020, 149: 55-62. DOI: 10.1016/j.radonc.2020.04.054http://dx.doi.org/10.1016/j.radonc.2020.04.054.

Eggold J T, Chow S, Melemenidis S, et al. Abdominopelvic FLASH irradiation improves PD-1 immune checkpoint inhibition in preclinical models of ovarian cancer[J]. Molecular Cancer Therapeutics, 2022, 21(2): 371-381. DOI: 10.1158/1535-7163.MCT-21-0358http://dx.doi.org/10.1158/1535-7163.MCT-21-0358.

Montay-Gruel P, Markarian M, Allen B D, et al. Ultra-high-dose-rate FLASH irradiation limits reactive gliosis in the brain[J]. Radiation Research, 2020, 194(6): 636-645. DOI: 10.1667/RADE-20-00067.1http://dx.doi.org/10.1667/RADE-20-00067.1.

Cunningham S, McCauley S, Vairamani K, et al. FLASH proton pencil beam scanning irradiation minimizes radiation-induced leg contracture and skin toxicity in mice[J]. Cancers, 2021, 13(5): 1012. DOI: 10.3390/cancers13051012http://dx.doi.org/10.3390/cancers13051012.

Velalopoulou A, Karagounis I V, Cramer G M, et al. FLASH proton radiotherapy spares normal epithelial and mesenchymal tissues while preserving sarcoma response[J]. Cancer Research, 2021, 81(18): 4808-4821. DOI: 10. 1158/0008-5472.CAN-21-1500http://dx.doi.org/10.1158/0008-5472.CAN-21-1500.

Schwarz M, Traneus E, Safai S, et al. Treatment planning for Flash radiotherapy: general aspects and applications to proton beams[J]. Medical Physics, 2022, 49(4): 2861-2874. DOI: 10.1002/mp.15579http://dx.doi.org/10.1002/mp.15579.

Esplen N, Mendonca M S, Bazalova-Carter M. Physics and biology of ultrahigh dose-rate (FLASH) radiotherapy: a topical review[J]. Physics in Medicine and Biology, 2020, 65(23): 23TR03. DOI: 10.1088/1361-6560/abaa28http://dx.doi.org/10.1088/1361-6560/abaa28.

张樱子, 姚升宇, 陈佳艺, 等. FLASH放疗技术相关热点分析[J]. 辐射研究与辐射工艺学报, 2020, 38(6): 060103. DOI: 10.11889/j.1000-3436.2020.rrj.38.060103http://dx.doi.org/10.11889/j.1000-3436.2020.rrj.38.060103.

ZHANG Yingzi, YAO Shengyu, CHEN Jiayi, et al. Hot spot analysis on FLASH radiotherapy technology[J]. Journal of Radiation Research and Radiation Processing, 2020, 38(6): 060103. DOI: 10.11889/j.1000-3436.2020.rrj.38.060103http://dx.doi.org/10.11889/j.1000-3436.2020.rrj.38.060103.

Tinganelli W, Sokol O, Quartieri M, et al. Ultra-high dose rate (FLASH) carbon ion irradiation: dosimetry and first cell experiments[J]. International Journal of Radiation Oncology, Biology, Physics, 2022, 112(4): 1012-1022. DOI: 10.1016/j.ijrobp.2021.11.020http://dx.doi.org/10.1016/j.ijrobp.2021.11.020.

Tashiro M, Yoshida Y, Oike T, et al. First human cell experiments with FLASH carbon ions[J]. Anticancer Research, 2022, 42(5): 2469-2477. DOI: 10.21873/anticanres.15725http://dx.doi.org/10.21873/anticanres.15725.

Zou W, Diffenderfer E S, Cengel K A, et al. Current delivery limitations of proton PBS for FLASH[J]. Radiotherapy and Oncology, 2021, 155: 212-218. DOI: 10.1016/j.radonc.2020.11.002http://dx.doi.org/10.1016/j.radonc.2020.11.002.

Farr J, Grilj V, Malka V, et al. Ultra-high dose rate radiation production and delivery systems intended for FLASH[J]. Medical Physics, 2022, 49(7): 4875-4911. DOI: 10.1002/mp.15659http://dx.doi.org/10.1002/mp.15659.

van Marlen P, Dahele M, Folkerts M, et al. Bringing FLASH to the clinic: treatment planning considerations for ultrahigh dose-rate proton beams[J]. International Journal of Radiation Oncology, Biology, Physics, 2020, 106(3): 621-629. DOI: 10.1016/j.ijrobp.2019.11.011http://dx.doi.org/10.1016/j.ijrobp.2019.11.011.

Kang M L, Wei S Y, Isabelle Choi J , et al. Quantitative assessment of 3D dose rate for proton pencil beam scanning FLASH radiotherapy and its application for lung hypofractionation treatment planning[J]. Cancers, 2021, 13(14): 3549. DOI: 10.3390/cancers13143549http://dx.doi.org/10.3390/cancers13143549.

van de Water S, Safai S, Schippers J M, et al. Towards FLASH proton therapy: the impact of treatment planning and machine characteristics on achievable dose rates[J]. Acta Oncologica, 2019, 58(10): 1463-1469. DOI: 10. 1080/0284186X.2019.1627416http://dx.doi.org/10.1080/0284186X.2019.1627416.

Krieger M, van de Water S, Folkerts M M, et al. A quantitative FLASH effectiveness model to reveal potentials and pitfalls of high dose rate proton therapy[J]. Medical Physics, 2022, 49(3): 2026-2038. DOI: 10.1002/mp.15459http://dx.doi.org/10.1002/mp.15459.

van Marlen P, Dahele M, Folkerts M, et al. Ultra-high dose rate transmission beam proton therapy for conventionally fractionated head and neck cancer: treatment planning and dose rate distributions[J]. Cancers, 2021, 13(8): 1859. DOI: 10.3390/cancers13081859http://dx.doi.org/10.3390/cancers13081859.

Wei S Y, Lin H B, Isabelle Choi J, et al. FLASH radiotherapy using single-energy proton PBS transmission beams for hypofractionation liver cancer: dose and dose rate quantification[J]. Frontiers in Oncology, 2022, 11: 813063. DOI: 10.3389/fonc.2021. 813063http://dx.doi.org/10.3389/fonc.2021.813063.

Wei S Y, Lin H B, Isabelle Choi J, et al. A novel proton pencil beam scanning FLASH RT delivery method enables optimal OAR sparing and ultra-high dose rate delivery: a comprehensive dosimetry study for lung tumors[J]. Cancers, 2021, 13(22): 5790. DOI: 10.3390/cancers13225790http://dx.doi.org/10.3390/cancers13225790.

Gao H, Liu J L, Lin Y T, et al. Simultaneous dose and dose rate optimization (SDDRO) of the FLASH effect for pencil-beam-scanning proton therapy[J]. Medical Physics, 2022, 49(3): 2014-2025. DOI: 10.1002/mp.15356http://dx.doi.org/10.1002/mp.15356.

van Marlen P, Verbakel W, Slotman B J, et al. Single-fraction 34 Gy lung stereotactic body radiation therapy using proton transmission beams: FLASH-dose calculations and the influence of different dose-rate methods and dose/dose-rate thresholds[J]. Advances in Radiation Oncology, 2022, 7(4): 100954. DOI: 10.1016/j.adro.2022.100954http://dx.doi.org/10.1016/j.adro.2022.100954.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

FLASH放疗技术相关热点分析

基于锥形束CT的直肠癌患者放疗中实际吸收剂量探讨

外泌体检测在肿瘤放化疗中的应用

PEI介导的E1A基因对结肠癌细胞放疗增敏效应的研究