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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 陳保中 | |
dc.contributor.author | Yu-Ling Lin | en |
dc.contributor.author | 林鈺琳 | zh_TW |
dc.date.accessioned | 2021-05-13T08:36:36Z | - |
dc.date.available | 2017-08-26 | |
dc.date.available | 2021-05-13T08:36:36Z | - |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-10 | |
dc.identifier.citation | 1. CM Vajdic, SP McDonald, MR McCredie, et al. Cancer incidence before and after kidney transplantation. JAMA 2006; 296: 2823–2831.
2. Harwood CA, Surentheran T, McGregor JM, et al. Human papillomavirus infection and non-melanoma skin cancer in immunosuppressed and immunocompetent individuals. J Med Virol 2000;61:289–297. 3. Kauffman HM, Cherikh WS, McBride MA, Cheng Y, Hanto DW. Post-transplant de novo malignancies in renal transplant recipients: the past and present. Transpl Int 2006;19:607–20. 4. Douros J, Suffness M. New antitumor substances of natural origin. Cancer Treat Rev 1981; 8: 63–87. 5. Lee JJ, Loh K, Yap YS. PI3K/Akt/mTOR inhibitors in breast cancer. Cancer Biol Med. 2015 Dec;12(4):342-54. 6. Chiang TL. Taiwan’s 1995 health care reform. Health Policy 1997;39:225–239 7. Bureau of National Health Insurance. Available from http://www.nhi.gov.tw/ Resource/webdata/Attach_13767_1_National% 20Health%20Insurance%20in% 20Taiwan%202010.pdf. Accessed 20 October 2011 8. Lu JF, Hsiao WC. Does universal health insurance make health care unaffordable? Lessons from Taiwan. Health Aff (Millwood) 2003;22:77–88 9. InstitutesNHR.NationalHealth Insurance Research Database. Available from http:// w3.nhri.org.tw/nhird/en/index.htm. Accessed 20 October 2011 10. Vajdic CM, McDonald SP, McCredie MR, et al. Cancer incidence before and after kidney transplantation. JAMA. 2006 Dec 20; 296(23): 2823-31. 11. Yanik EL, Siddiqui K, Engels EA. Sirolimus effects on cancer incidence after kidney transplantation: a meta-analysis. Cancer Med. 2015 Sep;4(9):1448-59. 12. Manuelli M, De Luca L, Iaria G, et al. Conversion to rapamycin immunosuppression for malignancy after kidney transplantation. Transplant Proc. 2010 May; 42(4): 1314-6. 13. Basu A, Liu T, Banerjee P, et al. Effectiveness of a combination therapy using calcineurin inhibitor and mTOR inhibitor in preventing allograft rejection and post-transplantation renal cancer progression. Cancer Lett. 2012 Aug 28; 321(2): 179-86. 14. Yanik EL, Gustafson SK, Kasiske BL, et al. Sirolimus use and cancer incidence among US kidney transplant recipients. Am J Transplant. 2015 Jan;15(1):129-36. 15. Gu Y-H, Du J-X, Ma M-L. Sirolimus and, non-melanoma skin cancer prevention after kidney transplantation: A meta-analysis. Asian Pac J Cancer Prev 2012; 13: 4335–39. 16. Pinto-Leite R, Arantes-Rodrigues R, Palmeira C, et al. Everolimus combined with cisplatin has a potential role in treatment of urothelial bladder cancer. Biomed Pharmacother. 2013 Mar;67(2):116-21. 17. Ashworth RE, Wu J. Mammalian target of rapamycin inhibition in hepatocellular carcinoma. World J Hepatol. 2014 Nov 27;6(11):776-82. 18. Kauffman HM, Cherikh WS, Cheng Y, Hanto DW, Kahan BD. Maintenance immunosuppression with target-of-rapamycin inhibitors is associated with a reduced incidence of de novo malignancies. Transplantation. 2005 Oct 15;80(7):883-9. 19. He K, Zheng X, Li M, Zhang L, Yu J. mTOR inhibitors induce apoptosis in colon cancer cells via CHOP-dependent DR5 induction on 4E-BP1 dephosphorylation. Oncogene. 2016 Jan 14;35(2):148-57. 20. Watorek E, Boratynska M, Smolska D, et al. Malignancy after renal transplantation in the new era of immunosuppression. Ann Transplant. 2011 Apr-Jun; 16(2):14-8. 21. Ikezawa E, Kondo T, Hashimoto Y, et al. Clinical symptoms predict poor overall survival in chronic-dialysis patients with renal cell carcinoma associated with end-stage renal disease. Jpn J Clin Oncol. 2014 Nov;44 (11):1096-100. 22. Tellis V, Schechner R, Mallis M, et al. No-load sirolimus with tacrolimus and steroids is safe and effective in renal transplantation. Transplant Proc 2005; 37:906-8. 23. Lo A, Egidi MF, Gaber LW, et al. Observations regarding the use of sirolimus and tacrolimus in high-risk cadaveric renal transplantation. Clin Transplant 2004; 18: 53-61. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/3769 | - |
dc.description.abstract | 研究背景
先前的研究指出mammalian target of rapamycin inhibitors (mTOR抑制劑)用在腎臟移植的患者身上,有抑制腫瘤的功效;然而mTOR抑制劑對全癌症發生率影響的程度,以至於對特定癌症發生率影響的程度,到死亡率的影響,目前仍是存在爭議,也因為mTOR抑制劑當中的sirolimus是2000年起開始上市使用,因此跟以往使用的免疫抑制劑間的交互作用仍未有定論。因此本篇研究藉由全民健保資料庫去分析,在腎臟移植患者身上,使用mTOR抑制劑與否以及使用的劑量多寡,對於全癌症、特定癌症及死亡率發生的影響程度。 研究方法 我們使用2000年到2008年間的全民健保資料庫中的重大傷病檔,選用其中末期腎臟病透析患者(ICD-9: 585)以及腎臟移植術後(ICD-9: V420)兩個族群進行世代研究。首先在配對年紀、性別、收入和地域性後,比較兩組癌症的發生率,接著選用一種常見的mTOR抑制劑藥物sirolimus當代表,並將腎臟移植術後的世代分成有使用過sirolimus和從未使用過sirolimus兩組,分析全癌症發生率、特定癌症發生率以及死亡率的影響,另外加入干擾因子進行敏感試驗分析,和分析不同sirolimus累積劑量對死亡率的影響。所有的統計分析是使用SAS 9.4進行。 研究結果 在腎臟移植的世代中發現,比起規則透析的世代有著較高癌症發生率,這個結果和之前的一些研究相似,但是本研究的結果在統計分析下是沒有顯著意義(HR 1.16 [95% CI 0.96–1.41],推論可能是因為2000年以後開始廣泛使用mTOR抑制劑的因素。再將腎臟移植的世代進一步分成有無使用sirolimus的兩個族群,發現使用sirolimus能降低全癌症、泌尿上皮細胞癌以及肝細胞癌的發生率,且皆有統計上顯著意義;只有大腸直腸癌的發生率呈現沒有統計顯著的上升。最後在死亡率部分,sirolimus可能會降低死亡率,而且在累積劑量的分層分析中顯示,隨著累積劑量愈大,愈能降低死亡率,但這些降低死亡率的結果均未達統計上顯著意義。 結論 mTOR抑制劑使用在腎臟移植後,能降低特定癌症的發生率,並可能改善腎臟移植患者的存活率,跟累積劑量可能也有相關性,但受限於本次世代研究的規模,有些結果並未能達統計學上的意義,因此仍需日後相關的研究協助探討。 | zh_TW |
dc.description.abstract | Background
Previous clinical studies suggested that mammalian target of rapamycin inhibitors (mTORi) had antineoplastic effects in renal transplantation cohort. However, overall cancer incidence and mortality rate in mTORi-exposed subjects post renal transplantation are equivocal. Objective We aimed to assess the association between the use of mTOR inhibitor and the risk of developing specific cancer types and mortality rate in renal transplantation cohort. RESEARCH DESIGN AND METHODS We conducted two nationwide, population based, cohort studies using the Taiwan National Health Insurance Research Database. In the first cohort, enrollees were defined as patients who received dialysis between 2000 and 2008. We separated this cohort into receiving renal transplantation group and dialysis group, which were matched by sex, age, income and area. Among the 9,394 eligible enrollees, we used Cox regression to assess the risk of cancer between two groups. The second cohort, subjects were defined as patients who received renal transplantation between 2000 and 2008. We separated the cohort into sirolimus-exposed subjects and sirolimus-unexposed subjects. We compared the overall cancer incidence, specific cancer types incidence and mortality rate between sirolimus-exposed subjects and sirolimus-unexposed subjects. RESULTS An increased risk of cancer was observed in patient post renal transplantation compared with those who in dialysis, although it was not significant (HR 1.16 [95% CI 0.96–1.41]. A decreased risk of cancer was observed in sirolimus-exposed subjects rather than sirolimus-unexposed subjects in renal transplantation subjects (crude HR 0.21 [95% CI 0.13–0.34]; adjusted HR 0.25 [95% CI 0.15–0.41]). Sirolimus-exposed subjects may decrease the incidence of urothelial cancer and hepatoma. Colorectal cancer showed an insignificant increased incidence in sirolimus-exposed subjects compared to sirolimus-unexposed subjects. We found lower mortality incidence in sirolimus-exposed subjects compared to sirolimus-unexposed subjects, although this difference was not significant. As sirolimus dosage increased, mortality incidence trended down. CONCLUSIONS The use of mTOR inhibitor may be associated with a decreased risk of cancer and mortality rate in patients post renal transplantation. Further studies are warranted to confirm our findings. | en |
dc.description.provenance | Made available in DSpace on 2021-05-13T08:36:36Z (GMT). No. of bitstreams: 1 ntu-105-R02841027-1.pdf: 457019 bytes, checksum: c06af95e642c6bc43a4782aefefadba0 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 中文摘要………………………………………………………………… i
英文摘要………………………………………………………………iii Chapter 1. Introduction……………………………………………1 1.1 Background………………………………………………………1 1.2 Purpose……………………………………………………………1 Chapter 2. Research design and methods………………………2 2.1 Study population………………………………………………3 2.2 Exposure and outcome definitions……………………………4 2.3 Statistical analyses……………………………………………4 Chapter 3. Results…………………………………………………… 6 Chapter 4. Discussion………………………………………………8 Chapter 5. Conclusions……………………………………………13 References………………………………………………………… 14 表目錄 Table 1. Characteristics in dialysis subjects and transplantation subjects…………17 Table 2. Overall cancer between dialysis subjects and transplantation subjects……18 Table 3. Characteristics in sirolimus-exposed subjects and sirolimus-unexposed subjects……………………………………………………………………..19 Table 4. Specific cancer types incidence associated with sirolimus exposure……20 Table 5. Sensitivity test for adjusted HRs of cancer in potentially confounding drugs …………………………………………………………………………………… 21 Table 6. Mortality rate associated with sirolimus exposure………………………22 Table 7. Mortality incidence associated with sirolimus cDDD……………………23 圖目錄 Figure 1. Survival curve associated with and without sirolimus-exposed………...24 | |
dc.language.iso | en | |
dc.title | mTOR抑制劑用於降低腎臟移植患者的癌症發生率與死亡率之研究 | zh_TW |
dc.title | The study of mammalian target of rapamycin (mTOR) inhibitors lower the incidence of malignancy and mortality rate in post-renal transplantation patient | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 楊垂勳,林建宇,王碩盟,沈麗娟 | |
dc.subject.keyword | mTOR抑制劑,癌症發生率,死亡率,腎臟移植,透析, | zh_TW |
dc.subject.keyword | mTOR inhibitor,cancer incidence,mortality rate,renal transplantation,dialysis, | en |
dc.relation.page | 24 | |
dc.identifier.doi | 10.6342/NTU201602214 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2016-08-10 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 職業醫學與工業衛生研究所 | zh_TW |
顯示於系所單位: | 職業醫學與工業衛生研究所 |
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