~（125）I粒子对人结肠腺癌（SW480）裸鼠皮下移植瘤增殖与凋亡的影响
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摘要
目的：通过建立人中分化结肠腺癌细胞(SW480)裸鼠皮下移植瘤模型,从增殖与凋亡两方面探讨碘-125(1251)粒子治疗中分化结肠腺癌的有效性及科学性。方法：将人结肠腺癌(SW480)细胞种植到雄性BALB/c-nu/nu裸小鼠皮下建立动物模型,随机将荷瘤裸小鼠分成对照组和实验组(每组24只),对照组与实验组各自再随机分成4组(每组6只),对照组植入空白粒子,实验组植入剂量为0.4mCi的125I粒子(1mCi=3.7×107Bq),观察粒子植入后瘤体生长情况,分别在植入后第7天、14天、21天、28天；按顺序处死实验组与对照组中第1、2、3、4组荷瘤裸鼠。剥取瘤体,分别用于流式细胞仪检测肿瘤细胞周期的再分布,免疫组化SP法测定增殖细胞核抗原的表达,透射电镜观察肿瘤细胞超微结构的改变,原位末端标记法检测肿瘤细胞原位凋亡情况。结果：随着放射时间的积累,流式细胞仪检测实验组肿瘤细胞周期被阻滞在G2/M期。增殖细胞核抗原标记指数(labelling index, LI)在第一周后,实验组中表达显著低于对照组(P<0.05),透射电镜示：实验组可见早中晚期凋亡细胞,对照组肿瘤细胞生长良好,少见细胞凋亡。TUNEL检测肿瘤细胞原位凋亡情况,实验组从第二周以后凋亡指数(Apoptosis index,AI)显著高于对照组,差异有统计学意义(P<0.05)。结论：1.125I粒子通过持续低剂量辐射使人中分化结肠腺癌(SW480)细胞周期阻滞在G2/M期,并下调PCNA的表达,是抑制人中分化结肠腺癌(SW480)增殖的重要生物学机制之一。2.125I粒子持续低剂量辐射可诱导人中分化结肠腺癌细胞(SW480)凋亡增加,且存在时-效关系。
Ojective:To discuss the effectiveness and scientific in nude mice bearing SW480 tumor treated with Iodine-125 brachytherapy.Methods:Taked the male nude mice of BLAB/c-nu/nu inoculated with human colon adenocarcinoma(SW480) cell as animal model. To be implanted iodine-125 seeds,the animal were divided into two groups (n=24), control groups and experiment group then randomly divided into 4 groups again (n=6).control group:to be implanted empty seeds, without iodine-125 radioelement(OmCi); experiment group:to be implanted iodine-125 seeds (0.4mCi),We observe the condition of tumor growth after implanted iodine-125. we killed 6 nude mice of each group in 7th、14th、21th、28th day after implantation, then we tested these implanted tumors by flow cytometer, transmission electron microscopy immunohistochemical and TUNEL respectively. Results:With the accumulation of radiation time, the tumor cells cycle in experiment group was blocked in G2/M phase.we can observe the early-mid-late period cell apoptosis in the experiment group by TEM,rare cell apoptosis were found in the control group. PCNA in the experiment group was significantly lower expression than it in corresponding control group after 1st week.(P＜0.05). TUNEL was used to detect apoptosis in situ. After the second week, the apoptosis index in the experiment group were significantly higher than the control group.Conclusions:1.one of the important biological mechanism to restrain the colon adenocarcinoma (SW480)is the iodine-125 seeds continuous low-dose radiationwas to block the cell cycle in G2/M phase and the proliferating cell nuclear antigen was inhibited.2. The continuous radiation in a low-doses with the iodine-125 seeds could induced cell apoptotic and exist the relationship of time-effect.
Ojective:To discuss the effectiveness and scientific in nude mice bearing SW480 tumor treated with Iodine-125 brachytherapy.Methods:Taked the male nude mice of BLAB/c-nu/nu inoculated with human colon adenocarcinoma(SW480) cell as animal model. To be implanted iodine-125 seeds,the animal were divided into two groups (n=24), control groups and experiment group then randomly divided into 4 groups again (n=6).control group:to be implanted empty seeds, without iodine-125 radioelement(OmCi); experiment group:to be implanted iodine-125 seeds (0.4mCi),We observe the condition of tumor growth after implanted iodine-125. we killed 6 nude mice of each group in 7th、14th、21th、28th day after implantation, then we tested these implanted tumors by flow cytometer, transmission electron microscopy immunohistochemical and TUNEL respectively. Results:With the accumulation of radiation time, the tumor cells cycle in experiment group was blocked in G2/M phase.we can observe the early-mid-late period cell apoptosis in the experiment group by TEM,rare cell apoptosis were found in the control group. PCNA in the experiment group was significantly lower expression than it in corresponding control group after 1st week.(P＜0.05). TUNEL was used to detect apoptosis in situ. After the second week, the apoptosis index in the experiment group were significantly higher than the control group.Conclusions:1.one of the important biological mechanism to restrain the colon adenocarcinoma (SW480)is the iodine-125 seeds continuous low-dose radiationwas to block the cell cycle in G2/M phase and the proliferating cell nuclear antigen was inhibited.2. The continuous radiation in a low-doses with the iodine-125 seeds could induced cell apoptotic and exist the relationship of time-effect.
引文
[1]Kemp Z, Thirlwell C, Sieber O, et al. An update onthe genetics of colorectal cancer[J]. Hum Mol Genet,2004,13:R177-R185.
[2]郁宝铭.结直肠癌外科治疗的现状和展望.中国普外基础与临床杂志,2008,9：631-636.
[3]Chedid A D,Villwock MM,Chedid M F,et al.Prognostic factors following liver resection for hepatic metastases from coloreetal cancer[J].Arq Gastroenterol,2003,40(3):159-165
[4]罗开元主编.实用组织间植入内放射治疗恶性肿瘤[M].北京：人民卫生出版社376-377
[5]Wolpin BM, Meyerhardt JA, Mamon H J, et al. Adjuvant Treatment of Colorectal Cancer [J].CA Cancer J Clin,2007,57(3):168-185.
[6]柴树德,郑广钧.粒子植入治疗胸部肿瘤[M].天津：天津科技出版社,2007：260-265.
[7]付改发,雷光焰,赵竹莲,等.125I新型粒子永久植入治疗恶性肿瘤的应用与观察[J].现代肿瘤医学,2004,12(2)：108-109.
[8]王俊杰,修典荣,冉维强.粒子组织间治疗肿瘤[M].第2版.北京：北京大学医学出版社,2004：49-56.
[9]Nasif WA, El-Emshaty HM, Lofty M, et al. Apoptosis dysregulation in human gastric carcinomas:relationship to anti-and pro-apoptofic protein expression [J]. Asian Pac J Cancer Prey,2007,8(1):45-50.
[10]Hacker G. The morphology of apoptosis[J]. Cell Tissue Res,2000,301(1):5-17.
[11]Arends MJ, Morris RG, Wyllie AH. Apoptosis:the role of the endonuclease[J]. Am J Pathol, 1990,136(3),593-608.
[12]Slattery ML, Sweeney C, Murtaugh M,et al.O1. Associations between ER alpha, ER beta, and AR genotypes and colon and rectal cancer[J]. Cancer Epidemiol Biomarkers Prey,2005, 14(12):2936-2942.
[13]黄志彪,黄俊明,熊习昆,等.SPF级实验动物房的建设及其管理.华南预防医学2005,6；72-74.
[14]Shimizu M, Saitoh Y, Itoh H, et al. Immunohistochemlcal staining of Ha-ras oncogene product in normal, benign, and malignant hmnan pancreatic tissues[J]. Human Pathology, 1990,21:607-809.
[151 Carlton CE Jr, Scardino PT. Combined interstitial and external irradiation for prostatic
cancer[J]. Pmg Clin Biol Res,1987,243B:141-169.
[16]Holm HH, Juul N, Pedersen JF, et al. Transperineal 125 iodine seed implantation in prostatic cancer guided by transrectal ultrasonography[J]. J Urol,1983,130(2):283-286
[17]Grimm PD, Blasko JC, Sylvester Je,et al.102Year biochemical(prostate specific antigen)control of prostate cancer with 1251 brachytherapy.Int J Radiat Oncol Biol Phys,2001,51:31-40
[18]罗开元主编.实用组织间植入内放射治疗恶性肿瘤[M].北京：人民卫生出版社39-40
[19]Hartwel LH, Kastan KB. Cell cycle control and cancer. Science.1994.266:1821.1828.
[20]Nasmyth K. Viewpoint:putting the eel cycle in order. Science,1996,274:1643.1645.
[21]Knox SJ, Sutherland W, Goris ML. Correlation of tumor sensitivity to low-dose-rale irradiation with G2/M-phase block and other radiobiological parameters[J]. Radiat Res.1993.135(1):24-31.
[22]Miyachi K,Fritzler MJ,Tan EM.Autoantibody to a nuclear antigen in proliferating cells. J Immunol,1978,121(6):2228-2234.
[23]Rizzo MG, Ottavio L, Travali S, et al. The promoter of the human Proliferating Cell Nuclear Antigen (PCNA)gene is bidirectional. Exp Cell Res.1990,188(2):286.293.
[24]BRAV0 R,FRANK R,BLUNDELL P A,et al.Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta[J].Nature,1987,326(6112):515-517.
[25]Lee CH, Lee MK, Kang CD, et al. Differential expression of hypoxia inducible factor-1 alpha and tumor cell proliferation between squamous cell carcinomas and adenocarcinomas among operable non-small cell lung carcinomas[J]. J Korean Med Sci,2003,18(2):196-203.
[26]Israels ED, G. Israels L. The cell cycle[J]. Fundamentals of Cancer Medicine,2001,19(1): 88-91.
[27]PRELICH G,K0STURA M.MARSHAK D R;et al.The cell-cycle regulated proliferating cell nuclear antigen is required for SV4O DNA replication in vitro[J]. Nature,1987, 326(6112):471-475.
[28]AL-Sheneber IF,Shibata HR,Sampalis J,et al.Prognostic significance of proliferating cell nuclear antigen expression in colorectal cancer [J]. Cancer.1993,71(6):1954-9.
[39]刘静贤,李吉友,张培荣等.大肠癌中CD4V6, P53, PCNA的表达及意义[J].肿瘤,2000,20(5)：362～364.
[30]魏道严,金敖兴,黄帼,等.小剂量辐射对小鼠肿瘤的抑制作用[J]。中华放射肿瘤学杂志。1995.4(4)：261
[31]Kerr JFR, Wyllie AH, Currie AR. Apoptosis:a basic biological phenomenon with wideranging implications in tissue kinetics[J]. Br J Cancer,1972,26:239.
[32]Gong S L, Liu S C, Liu J X, et al。Adaptive response of thymocyte apoptosis and cell cycle progression induced by low dose X-ray irradiation in mice[J]. Biomed Envir-on Sci,2000, 13(3):180-188.
[33]王嘉宁,郭宁等.细胞凋亡的检测技术与方法[J].中国药理学与毒理学杂志,2005,19(6)：466-470
[34]Kroger LA, Denardo GL, Gumer lock PH, et al. Apoptosis-related gene and protein expression in human lymphoma xenografis(Raji)after low dose rate radiation using 67Cu-21T-BAT-Lym-1 radioimmu-notherapy[J]. Cancer Biother Radiopharm 2001,16(3):213-225.
[35]zou JP,shimjzu J,Ikegame K,Takiuchi H,Fujiwara H, Hamaoka T.Tumor immunotherapy with the use of tumor-antigen-pulsed antigen-presenting cells.Cancer Immunol Immunother 1992: 35:1-6
[1]Sean Garrean, Amanda Muhs,et al,Complete eradication of hepatic metastasis from colorectal cancer by Yttrium-90 SIRT[J]. World J Gastroenterol 2007 June 7; 13(21): 3016-3019. PMID:17589957
[2]Rafael Martinez-Monge, Subir Nag, et al. Three Different Intraoperative Radiation Modalities(Electron Beam, High-Dose-Rate Brachytherapy, and Iodine-125 Brachytherapy) in the Adjuvant Treatmentof Patients with Recurrent Colorectal Adenocarcinoma[J]. CANCER July 15,1999;236-247. PMID:10421259
[3]周飞国,晏建军,黄亮等,Iodine-125 interstitial brachytherapy for experimental liver cancer[J].中国人民解放军军医大学学报英文版2007；22(2)87-91
[4]Lawrence TS, Robertson JM, Anscher MS, et al, Hepatic toxicity resulting from cancer treatment[J]. Int J Radiat Oncol Biol Phys 1995; 31:1237-1248. PMID:7713785
[5]Martinez-Monge R,Nag S,Nieroda CA. et al,Iodine-125 Brachytherapy in the Treatment of Colorectal Adenocarcinoma Metastatic to the Liver[J]. Cancer.1999 Mar 15;85(6):1218-25. PMID:10189125
[6]Nag S, DeHaan M, Scruggs G, et al, long-term follow-up of patients of intrahepatic malignancies treated with iodine-125 brachytherapy [J]. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):736-44. PMIQ:16274935
【7】 蒋小良,90Y治疗肝癌的研究进展[J].放射学实践,2006年1月第21卷第1期 106-108.
[8]Salem R, Thurston KG, Carr BI, et al. Yttrium-90 microspheres:radiation therapy for unresectable liver cancer[J]. J Vasc Interv Radiol 2002; Sep 13:S223-S229. PMID: 12354840
[9]King J,Quinn R.Radioembolization with selective internal radiation microspheres for neuroendocrine live metastases[J].cancer 2008 Sepl;113:921-9. PMID:18618495
[10]Hong K,Georgiades CS,Geschwind JF.Technology insight:Image-guided therapies for hepatocellular carcinoma--intra-arterial and ablative techniques[J] Nat Clin Pract Oncol. 2006 Jun;3(6):315-24. Review. PMID:16757969
[11]Simmonds PC, Primrose JN, Colquitt JL, et al. Surgical resection of hepatic metastases from colorectal cancer:a systematic review of published studies[J]. Br J Cancer.2006 Apr 10;94(7):982-99. Review. PMID:16538219
【12】罗开元实用组织间植入内放射治疗恶性肿瘤学[M].第一版.北京：人民卫生出版社,2008：49.
【13】罗开元,李波,杨嵘,等.125I粒子组织间放射治疗恶性肿瘤的临床应用[J].中华医学杂志,2001,81(12)：754 755.
[14]Ibrahim SM, Lewandowski RJ, Sato KT, Radioembolization for the treatment of unresectable hepatocellular carcinoma:A clinical review[J]. World J Gastroenterol 2008 March 21; 14(11):1664-1669. PMID:18350597
[15]Price TJ,TOWNSEND A. Yttrium 90 Microsphere Selective Internal Radiation Treatment of Hepatic Colorectal Metastases[J]. Arch Surg.2008 Mar;143(3):313-4. Review. PMID: 18347282
[16]Gray BN et al. Tolerance of the liver to the effects of Yttrium-90 radiation[J]. Int J Radiat Oncol Biol Phys. (1990);18(3):619-623. PMID:2318695
[17]Mishra MV,Shirazi R, et al. Incidence and clinical course of hemorrhagic radiation proctitis after iodine-125 prostate brachytherapy[J]. Clin Genitourin Cancer.2007 Sep;5(6):397-400. PMID:17956713
[18]Rougier P, Mitry E, Barbare JC, Taieb J. Hepatocellular carcinoma (HCC):an update[J]. Semin Oncol.2007 Apr;34(2 Suppl 1);S12-20. Review. PMID:17449346
[2]郁宝铭.结直肠癌外科治疗的现状和展望.中国普外基础与临床杂志,2008,9：631-636.
[3]Chedid A D,Villwock MM,Chedid M F,et al.Prognostic factors following liver resection for hepatic metastases from coloreetal cancer[J].Arq Gastroenterol,2003,40(3):159-165
[4]罗开元主编.实用组织间植入内放射治疗恶性肿瘤[M].北京：人民卫生出版社376-377
[5]Wolpin BM, Meyerhardt JA, Mamon H J, et al. Adjuvant Treatment of Colorectal Cancer [J].CA Cancer J Clin,2007,57(3):168-185.
[6]柴树德,郑广钧.粒子植入治疗胸部肿瘤[M].天津：天津科技出版社,2007：260-265.
[7]付改发,雷光焰,赵竹莲,等.125I新型粒子永久植入治疗恶性肿瘤的应用与观察[J].现代肿瘤医学,2004,12(2)：108-109.
[8]王俊杰,修典荣,冉维强.粒子组织间治疗肿瘤[M].第2版.北京：北京大学医学出版社,2004：49-56.
[9]Nasif WA, El-Emshaty HM, Lofty M, et al. Apoptosis dysregulation in human gastric carcinomas:relationship to anti-and pro-apoptofic protein expression [J]. Asian Pac J Cancer Prey,2007,8(1):45-50.
[10]Hacker G. The morphology of apoptosis[J]. Cell Tissue Res,2000,301(1):5-17.
[11]Arends MJ, Morris RG, Wyllie AH. Apoptosis:the role of the endonuclease[J]. Am J Pathol, 1990,136(3),593-608.
[12]Slattery ML, Sweeney C, Murtaugh M,et al.O1. Associations between ER alpha, ER beta, and AR genotypes and colon and rectal cancer[J]. Cancer Epidemiol Biomarkers Prey,2005, 14(12):2936-2942.
[13]黄志彪,黄俊明,熊习昆,等.SPF级实验动物房的建设及其管理.华南预防医学2005,6；72-74.
[14]Shimizu M, Saitoh Y, Itoh H, et al. Immunohistochemlcal staining of Ha-ras oncogene product in normal, benign, and malignant hmnan pancreatic tissues[J]. Human Pathology, 1990,21:607-809.
[151 Carlton CE Jr, Scardino PT. Combined interstitial and external irradiation for prostatic
cancer[J]. Pmg Clin Biol Res,1987,243B:141-169.
[16]Holm HH, Juul N, Pedersen JF, et al. Transperineal 125 iodine seed implantation in prostatic cancer guided by transrectal ultrasonography[J]. J Urol,1983,130(2):283-286
[17]Grimm PD, Blasko JC, Sylvester Je,et al.102Year biochemical(prostate specific antigen)control of prostate cancer with 1251 brachytherapy.Int J Radiat Oncol Biol Phys,2001,51:31-40
[18]罗开元主编.实用组织间植入内放射治疗恶性肿瘤[M].北京：人民卫生出版社39-40
[19]Hartwel LH, Kastan KB. Cell cycle control and cancer. Science.1994.266:1821.1828.
[20]Nasmyth K. Viewpoint:putting the eel cycle in order. Science,1996,274:1643.1645.
[21]Knox SJ, Sutherland W, Goris ML. Correlation of tumor sensitivity to low-dose-rale irradiation with G2/M-phase block and other radiobiological parameters[J]. Radiat Res.1993.135(1):24-31.
[22]Miyachi K,Fritzler MJ,Tan EM.Autoantibody to a nuclear antigen in proliferating cells. J Immunol,1978,121(6):2228-2234.
[23]Rizzo MG, Ottavio L, Travali S, et al. The promoter of the human Proliferating Cell Nuclear Antigen (PCNA)gene is bidirectional. Exp Cell Res.1990,188(2):286.293.
[24]BRAV0 R,FRANK R,BLUNDELL P A,et al.Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta[J].Nature,1987,326(6112):515-517.
[25]Lee CH, Lee MK, Kang CD, et al. Differential expression of hypoxia inducible factor-1 alpha and tumor cell proliferation between squamous cell carcinomas and adenocarcinomas among operable non-small cell lung carcinomas[J]. J Korean Med Sci,2003,18(2):196-203.
[26]Israels ED, G. Israels L. The cell cycle[J]. Fundamentals of Cancer Medicine,2001,19(1): 88-91.
[27]PRELICH G,K0STURA M.MARSHAK D R;et al.The cell-cycle regulated proliferating cell nuclear antigen is required for SV4O DNA replication in vitro[J]. Nature,1987, 326(6112):471-475.
[28]AL-Sheneber IF,Shibata HR,Sampalis J,et al.Prognostic significance of proliferating cell nuclear antigen expression in colorectal cancer [J]. Cancer.1993,71(6):1954-9.
[39]刘静贤,李吉友,张培荣等.大肠癌中CD4V6, P53, PCNA的表达及意义[J].肿瘤,2000,20(5)：362～364.
[30]魏道严,金敖兴,黄帼,等.小剂量辐射对小鼠肿瘤的抑制作用[J]。中华放射肿瘤学杂志。1995.4(4)：261
[31]Kerr JFR, Wyllie AH, Currie AR. Apoptosis:a basic biological phenomenon with wideranging implications in tissue kinetics[J]. Br J Cancer,1972,26:239.
[32]Gong S L, Liu S C, Liu J X, et al。Adaptive response of thymocyte apoptosis and cell cycle progression induced by low dose X-ray irradiation in mice[J]. Biomed Envir-on Sci,2000, 13(3):180-188.
[33]王嘉宁,郭宁等.细胞凋亡的检测技术与方法[J].中国药理学与毒理学杂志,2005,19(6)：466-470
[34]Kroger LA, Denardo GL, Gumer lock PH, et al. Apoptosis-related gene and protein expression in human lymphoma xenografis(Raji)after low dose rate radiation using 67Cu-21T-BAT-Lym-1 radioimmu-notherapy[J]. Cancer Biother Radiopharm 2001,16(3):213-225.
[35]zou JP,shimjzu J,Ikegame K,Takiuchi H,Fujiwara H, Hamaoka T.Tumor immunotherapy with the use of tumor-antigen-pulsed antigen-presenting cells.Cancer Immunol Immunother 1992: 35:1-6
[1]Sean Garrean, Amanda Muhs,et al,Complete eradication of hepatic metastasis from colorectal cancer by Yttrium-90 SIRT[J]. World J Gastroenterol 2007 June 7; 13(21): 3016-3019. PMID:17589957
[2]Rafael Martinez-Monge, Subir Nag, et al. Three Different Intraoperative Radiation Modalities(Electron Beam, High-Dose-Rate Brachytherapy, and Iodine-125 Brachytherapy) in the Adjuvant Treatmentof Patients with Recurrent Colorectal Adenocarcinoma[J]. CANCER July 15,1999;236-247. PMID:10421259
[3]周飞国,晏建军,黄亮等,Iodine-125 interstitial brachytherapy for experimental liver cancer[J].中国人民解放军军医大学学报英文版2007；22(2)87-91
[4]Lawrence TS, Robertson JM, Anscher MS, et al, Hepatic toxicity resulting from cancer treatment[J]. Int J Radiat Oncol Biol Phys 1995; 31:1237-1248. PMID:7713785
[5]Martinez-Monge R,Nag S,Nieroda CA. et al,Iodine-125 Brachytherapy in the Treatment of Colorectal Adenocarcinoma Metastatic to the Liver[J]. Cancer.1999 Mar 15;85(6):1218-25. PMID:10189125
[6]Nag S, DeHaan M, Scruggs G, et al, long-term follow-up of patients of intrahepatic malignancies treated with iodine-125 brachytherapy [J]. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):736-44. PMIQ:16274935
【7】 蒋小良,90Y治疗肝癌的研究进展[J].放射学实践,2006年1月第21卷第1期 106-108.
[8]Salem R, Thurston KG, Carr BI, et al. Yttrium-90 microspheres:radiation therapy for unresectable liver cancer[J]. J Vasc Interv Radiol 2002; Sep 13:S223-S229. PMID: 12354840
[9]King J,Quinn R.Radioembolization with selective internal radiation microspheres for neuroendocrine live metastases[J].cancer 2008 Sepl;113:921-9. PMID:18618495
[10]Hong K,Georgiades CS,Geschwind JF.Technology insight:Image-guided therapies for hepatocellular carcinoma--intra-arterial and ablative techniques[J] Nat Clin Pract Oncol. 2006 Jun;3(6):315-24. Review. PMID:16757969
[11]Simmonds PC, Primrose JN, Colquitt JL, et al. Surgical resection of hepatic metastases from colorectal cancer:a systematic review of published studies[J]. Br J Cancer.2006 Apr 10;94(7):982-99. Review. PMID:16538219
【12】罗开元实用组织间植入内放射治疗恶性肿瘤学[M].第一版.北京：人民卫生出版社,2008：49.
【13】罗开元,李波,杨嵘,等.125I粒子组织间放射治疗恶性肿瘤的临床应用[J].中华医学杂志,2001,81(12)：754 755.
[14]Ibrahim SM, Lewandowski RJ, Sato KT, Radioembolization for the treatment of unresectable hepatocellular carcinoma:A clinical review[J]. World J Gastroenterol 2008 March 21; 14(11):1664-1669. PMID:18350597
[15]Price TJ,TOWNSEND A. Yttrium 90 Microsphere Selective Internal Radiation Treatment of Hepatic Colorectal Metastases[J]. Arch Surg.2008 Mar;143(3):313-4. Review. PMID: 18347282
[16]Gray BN et al. Tolerance of the liver to the effects of Yttrium-90 radiation[J]. Int J Radiat Oncol Biol Phys. (1990);18(3):619-623. PMID:2318695
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