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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 | 楊偉勛(Wei-Shiung Yang) | |
dc.contributor.author | Chen-Yu Lo | en |
dc.contributor.author | 羅晨瑀 | zh_TW |
dc.date.accessioned | 2021-06-08T02:49:19Z | - |
dc.date.copyright | 2017-09-13 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-17 | |
dc.identifier.citation | 1. Fung, M.M., O.H. Viveros, and D.T. O'Connor, Diseases of the adrenal medulla. Acta Physiol (Oxf), 2008. 192(2): p. 325-35.
2. Ait-Ali, D., et al., PACAP-cytokine interactions govern adrenal neuropeptide biosynthesis after systemic administration of LPS. Neuropharmacology, 2010. 58(1): p. 208-14. 3. Lau SK, R. SG, and W. LM, Sustentaculoma: report of a case of a distinctive neoplasm of the adrenal medulla. The American Journal of Surgical Pathology., 2006. 30(2): p. 268-73. 4. DT, O.C., et al., The adrenal medulla, catecholamines, and phaeochromocytoma. Cecil’s Textbook of Medicine. 2003. 1419–1424. 5. PP, S. and B. HR, A simplified diagnostic approach to pheochromocytoma. A review of the literature and report of one institution's experience. Medicine (Baltimore), 1991. 70(1): p. 46-66. 6. K, P., et al., Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med, 2001. 134(4): p. 315-29. 7. HP1, N., et al., Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease. N Engl J Med, 1993. 329(21): p. 1531-8. 8. ER, M., et al., Clinical features and natural history of von Hippel-Lindau disease. Q J Med, 1990. 77(283): p. 1151-63. 9. HP, N., et al., Evidence of MEN-2 in the original description of classic pheochromocytoma. N Engl J Med, 2007. 357(13): p. 1311-5. 10. RA, D., et al., WHO Classification of Tumours. Pathology and Genetics of Tumours of the Endocrine Organs. 2004. 11. Fishbein, L., et al., Inherited mutations in pheochromocytoma and paraganglioma: why all patients should be offered genetic testing. Ann Surg Oncol, 2013. 20(5): p. 1444-50. 12. Burnichon, N., et al., SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet, 2010. 19(15): p. 3011-20. 13. Welander, J., P. Soderkvist, and O. Gimm, Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. Endocr Relat Cancer, 2011. 18(6): p. R253-76. 14. L, B., et al., In: World Health Organization Classification of Tumours. Pathology & Genetics Head and Neck Tumours. 2005. 15. van Duinen, N., et al., Increased urinary excretion of 3-methoxytyramine in patients with head and neck paragangliomas. J Clin Endocrinol Metab, 2010. 95(1): p. 209-14. 16. Lee, J.A. and Q.Y. Duh, Sporadic paraganglioma. World J Surg, 2008. 32(5): p. 683-7. 17. Simpson, L.N., et al., Catecholamine-secreting paraganglioma of the thoracic spinal column: report of an unusual case and review of the literature. Neurosurgery, 2012. 70(4): p. E1049-52; discussion E1052. 18. Chen, H., et al., The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas, 2010. 39(6): p. 775-83. 19. CM, B., et al., Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proc, 1983. 58(12): p. 802-4. 20. Guerrero, M.A., et al., Clinical spectrum of pheochromocytoma. J Am Coll Surg, 2009. 209(6): p. 727-32. 21. Bjorklund, P. and S. Backman, Epigenetics of pheochromocytoma and paraganglioma. Mol Cell Endocrinol, 2017. 22. M, A.-H., et al., Comparison of pheochromocytomas and abdominal and pelvic paragangliomas with head and neck paragangliomas. Endocr Pract, 2009. 15(3): p. 194-202. 23. Boedeker, C.C., et al., Malignant head and neck paragangliomas in SDHB mutation carriers. Otolaryngol Head Neck Surg, 2007. 137(1): p. 126-9. 24. Bravo, E.L., Pheochromocytoma: New concepts and future trends. Kidney International, 1991. 40(3): p. 544-556. 25. Ayadi-Kaddour, A., et al., Posterior mediastinal paragangliomas: a report of three patients with peculiar tumours. Respirology, 2009. 14(3): p. 459-61. 26. Ghayee, H.K., et al., Mediastinal paragangliomas: association with mutations in the succinate dehydrogenase genes and aggressive behavior. Endocr Relat Cancer, 2009. 16(1): p. 291-9. 27. D, E., et al., Benign paragangliomas: clinical presentation and treatment outcomes in 236 patients. J Clin Endocrinol Metab, 2001. 86(11): p. 5210-6. 28. HM, L., et al., Anterior mediastinal paraganglioma mimicking thymoma. Heart Surg Forum, 2012. 15(3): p. E170-1. 29. Lenders, J.W., et al., Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab, 2014. 99(6): p. 1915-42. 30. Kirmani, S., MBBS, and M. William F Young, MSc., GeneReviews® [Internet]. 2008. 31. Noda, T., et al., Successful outcome after resection of liver metastasis arising from an extraadrenal retroperitoneal paraganglioma that appeared 9 years after surgical excision of the primary lesion. Int J Clin Oncol, 2009. 14(5): p. 473-7. 32. Fishbein, L., et al., External Beam Radiation Therapy (EBRT) for Patients with Malignant Pheochromocytoma and Non-Head and -Neck Paraganglioma: Combination with 131I-MIBG. 2012. 44(05): p. 405-410. 33. McBride, J.F., et al., Minimally invasive treatment of metastatic pheochromocytoma and paraganglioma: efficacy and safety of radiofrequency ablation and cryoablation therapy. J Vasc Interv Radiol, 2011. 22(9): p. 1263-70. 34. Chromosome 11 monosomy in conjunction with a mutated SDHD initiation codon in nonfamilial paraganglioma cases. 2004. 35. RF1, B., et al., Novel mutations in the SDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss. Genes Chromosomes Cancer, 2001. 31(3): p. 255-63. 36. Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytomas. 2003. 37. Adrenal Medulla. NIH - National Cancer Institute. 38. Pheochromocytoma and Paraganglioma Treatment (PDQ®)–Patient Version. 2016. 39. WF, Y., Williams Textbook of Endocrinology 13th Edition. 2015. 40. Proposed genetic testing algorithm for patients with pheochromocytoma/paraganglioma based on clinical features. 41. Adjalle, R., et al., Treatment of malignant pheochromocytoma. Horm Metab Res, 2009. 41(9): p. 687-96. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20456 | - |
dc.description.abstract | 嗜鉻細胞瘤(Pheochromocytoma)和副神經節瘤(Paraganglioma)是分別起源於腎上腺髓質或腎上腺外交感神經的腫瘤,前者主要合成和分泌兒茶酚胺(Catecholamine),如去甲腎上腺素(norepinephrine)、腎上腺素(epinephrine)、多巴胺(Dopamine),後者的大量釋放引起症狀,進而引起患者會出現有高血壓、陣發性頭痛、出汗、心悸等臨床症狀,並造成心、腦、腎等嚴重併發症。
本論文因收集嗜鉻細胞瘤/副神經節瘤患者的DNA進行基因檢測的時間為2010年,當時只知這兩種疾病的基因突變有關的基因為RET、VHL、SDHB、SDHC、SDHD,而至今已知與其疾病的基因突有關的基因增加為SDHA、NF1、KIF1B、MAX、TMEM127,共10種基因相關,目前嗜鉻細胞瘤/副神經節瘤患者可由臨床症狀去進行基因檢測方法,只針對7位受試者進行5個基因檢測,其中有找到突變點位為5/7(佔67%),另外沒有找到突變點位為2/7(佔33%);在7名患者中,有5位的基因檢測找到基因點位,且這5位患者皆有臨床上發現頸部頸部或下巴有腫塊的症狀,有1位發現在SDHB基因突變和有4位發現在SDHD基因突變。 這種在基因型和表現型之間,有密切關聯的腫瘤症候群,希望能夠建立分子生物基因檢測和遺傳諮詢的模式,以便於已經出現症狀的患者和家族中可能有其他潛在潛在的患者患者,提供必要的基因檢測、給予適當的醫療,在遺傳諮詢同時,可再教育患者及家屬嗜鉻細胞瘤和/或副神經節瘤發生的原因,以及對此疾病有正確的認識。 | zh_TW |
dc.description.abstract | Pheochromocytoma and paraganglioma are tumors that originate from adrenal medulla or adrenal gonadal ganglion. The mainly synthesizing and secreting large amounts of catecholamine, such as norepinephrine, epinephrine. For these two diseases, main symptoms are hypertension, paroxysmal headache, sweating, palpitations and other clinical symptoms, and cause heart, brain, kidney and other serious complications.
In this thesis, we enrolled the patients with pheochromocyroma/ paraganglioma in 2010, and extracted their DNA form PBMC (peripheral blood mononuclear cell). At that time, we only know these two diseases related to RET, VHL, SDHB, SDHC, SDHD. However, with the progress of genetic medicine, we found that SDHA, NF1, KIF1B, MAX, and TMEM127 were also related to these two diseases. At present, pheochromocytoma / paraganglioma patients can be carried out by clinical symptoms of genetic testing methods. We only tested these 7 patients with previous 5 genes, and found a detection rate with 67% (5/7); the other two patients didn’t find any variants in these 5 genes. There are five genes that detect gene mutation in 7 subjects, and they all have clinical symptoms. We found one mutation in the SDHB gene and was found in the SDHD gene mutation with 4 subjects. Between the genotypes and phenotypes, there are close associated tumor syndromes. I hope to establish a molecular gene detection and a genetic counseling model. Therefore, we can provide necessary genetic testing and proper medical care for those patients and their families. At the same time, we can educate patients and their families about the causes of pheochromocytoma / paraganglioma, and have a correct understanding of the disease. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T02:49:19Z (GMT). No. of bitstreams: 1 ntu-106-P98448002-1.pdf: 2915778 bytes, checksum: 96c2b3b4e65b66a44db8d8036296e209 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 審定書 I
致謝 II 中文摘要 III Abstract IV 目 錄 VI 圖目錄 VIII 表目錄 IX 第一章 緒論 1 1.1 腎上腺髓質疾病(Diseases of the adrenal medulla) 1 1.1.1 疾病簡介 1 1.1.2 解剖學和生理學 2 1.2 嗜鉻細胞瘤(Pheochromocytoma) 3 1.2.1 疾病發現起源 3 1.2.2 疾病分型原則 4 1.2.3 多發性內分泌腫瘤第二型 5 1.3 副神經節瘤(Paraganglioma) 7 1.3.1 疾病發現起源 7 1.3.2 疾病定義 7 1.4 嗜鉻細胞瘤/副神經節瘤基因型表現及相關性 (Genotype and Correlation) 8 第二章 研究背景與動機 10 2.1 嗜鉻細胞瘤/副神經節瘤的遺傳學及流行病學 10 2.1.1 嗜鉻細胞瘤 10 2.1.2 副神經節瘤 10 2.2 嗜鉻細胞瘤/副神經節瘤的臨床表現 11 2.2.1 嗜鉻細胞瘤 11 2.2.2 副神經節瘤 12 2.3 嗜鉻細胞瘤/副神經節瘤的檢驗方式 13 2.3.1 實驗室生化檢查 13 2.3.2 影像檢查 13 2.3.3 基因檢查 14 2.3.4 切片檢查 16 2.4 疾病治療與預後 17 2.4.1 局部治療 17 2.4.2 全身治療 18 第三章 研究材料與儀器 19 3.1 受試者DNA 19 3.2 引子對(primer) 19 3.3 聚合酶連鎖反應試劑 19 3.4 實驗儀器 19 第四章 研究方法 20 4.1 DNA萃取 20 4.2 聚合酶連鎖反應(Polymerase Chain Reaction, PCR) 21 4.3 基因序列分析(DNA Sequencing) 22 第五章 實驗結果 23 5.1臨床表現資料收集及結果 23 5.2 基因之統整分析結果 25 第七章 討論 27 第八章 遺傳諮詢 28 第九章 參考文獻 30 圖目錄 圖一 腎上腺髓質 36 圖二 副神經節瘤 36 圖三 受試者No.1之基因突變點位 37 圖四 受試者No.3之基因突變點位 37 圖五 受試者No.4之基因突變點位 38 圖六 受試者No.5之基因突變點位 38 圖七 受試者No.6之基因突變點位 39 圖八 基因突變分佈 40 表目錄 表一 嗜鉻細胞瘤和副神經節瘤相關基因突變 42 表二 基因所有Exon之理想反應試劑條件 43 表三 聚合酶連鎖反應之理想反應參數 43 表四 基因的PCR條件及產物長度和溫度 44 表五 SDHD基因的cDNA 45 表六 SDHB基因的cDNA 46 表七 SDHD基因序列位置 46 表八 SDHB基因序列位置 47 表九 本論文基因的突變點位 48 表十 嗜鉻細胞瘤/副神經節瘤患者目前臨床特徵的遺傳檢測方法 48 表十一 嗜鉻細胞瘤和副神經節瘤的治療方法 49 | |
dc.language.iso | zh-TW | |
dc.title | 嗜鉻細胞瘤和/或副神經節瘤的基因檢測與遺傳諮詢 | zh_TW |
dc.title | Genetic testing and counseling for patients with pheochromocytoma and / or paraganglioma | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 陳沛隆(Pei-Lung Chen) | |
dc.contributor.oralexamcommittee | 施翔蓉 | |
dc.subject.keyword | 腎上腺,嗜鉻細胞瘤,副神經節瘤,兒茶酚胺,腎上腺素, | zh_TW |
dc.subject.keyword | Adrenal medulla,Pheochromocytoma,Paraganglioma,Catecholamine,Epinephrine, | en |
dc.relation.page | 49 | |
dc.identifier.doi | 10.6342/NTU201703759 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2017-08-17 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
顯示於系所單位: | 分子醫學研究所 |
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