一馬兜鈴酸尿路上皮病變之研究.
二腎移植病患新藥治療及巨細胞病毒感染之探討

張浤榮

doi:10.6834/CSMU.2006.00117

18.232.59.38，Hello！

Close
Search Quick Search Advanced Search Publication Search	Personal Service Member Login Searching History Use Bonus Card SYMSKAN
Browse Browse by University of Graduate Thesis Browse by Pinyin of Graduate Thesis Browse by Conference Proceedings Topic Browse by Conference Proceedings Publisher Browse by Pinyin of Conference Proceedings Browse by eBook Category Browse by eBook Topic Browse by eBook Publisher
Customer Services Authorize Airiti Recommend a Journal

Search Symbol (Half-width)	Description of Search Symbols
Space	"AND" indicates the intertwining of key terms used in a search
Double Quotation Marks ("") ( " " )	Double quotation marks indicate the beginning and end of a phrase, and the search will only include terms that appear in the same order of those within the quotations. Example: "image process" ： " image process "
?	Indicates a variable letter. Entering two ? will indicate two variable letters, and so on. Example: "Appl?", search results will yield apple, apply… e , appl y … ( (often used to English word searches) )
*	Indicates an unlimited number of variable letters to follow, from 1~n. Example: Enter "appl*", search results will yield apple, apples, apply, applied, application…(often used in English word searches) e , appl es , appl y , appl ied , appl ication … ( (often used to English word searches) )
AND、OR、NOT	Boolean logic combinations of key words is a skill used to expand or refine search parameters. (1) AND (1) AND: Refines search parameters (2) OR (2) OR: Expands search parameters (3) NOT: Excludes irrelevant parameters

DOI stands for Digital Object Identifier （ D igital O bject I dentifier ） ,
and is the unique identifier for objects on the internet. It can be used to create persistent link and to cite articles.

Using DOI as a persistent link

To create a persistent link, add「http://dx.doi.org/」「 http://dx.doi.org/ 」 before a DOI.
For instance, if the DOI of an article is 10.5297/ser.1201.002 , you can link persistently to the article by entering the following link in your browser: http://dx.doi.org/ 10.5297/ser.1201.002 。
The DOI link will always direct you to the most updated article page no matter how the publisher changes the document's position, avoiding errors when engaging in important research.

Cite a document with DOI

When citing references, you should also cite the DOI if the article has one. If your citation guideline does not include DOIs, you may cite the DOI link.

DOIs allow accurate citations, improve academic contents connections, and allow users to gain better experience across different platforms. Currently, there are more than 70 million DOIs registered for academic contents. If you want to understand more about DOI, please visit airiti DOI Registration （ doi.airiti.com ）。

Data Source

Health & Medical Care > Medical Sciences
College of Medicine > Graduate Institute of Medicine

Bibliography Management Tool

Related Links

Report an Issue

Purchase Single Articles

Download PDF

一馬兜鈴酸尿路上皮病變之研究. 二腎移植病患新藥治療及巨細胞病毒感染之探討

1.Aristolochic acid-induced urothelial proliferation in rats. 2. Studies on newer immunosuppressants and cytomegalovirus infection in kidney transplantation

張浤榮 , Ph.D　　Advisor：王朝鐘;連榮達　　

繁體中文 DOI： 10.6834/CSMU.2006.00117

馬兜鈴酸；細胞週期；泌尿上皮增生；腎臟移植；免疫抑制劑；巨細胞病毒. ； aristolochic acid ； cell cycle ； urothelial proliferation ； kidney transplantation, immunosuppressant ； cytomegalovirus.

Abstract │ Reference (135) │ Altmetrics

Abstract 〈TOP〉

第一部份
馬兜鈴酸(aristolochic acid)已被證實與人類尿路上皮癌(urothelial carcinoma)有關，但其真正致癌機轉仍未完全瞭解。為評估馬兜鈴酸對老鼠膀胱上皮的影響，我們進行一個以胃管餵食馬兜鈴酸三個月的老鼠實驗，所餵食的馬兜鈴酸混合液為含有41%第一型馬兜鈴酸(aristolochic acid I)以及56%第二型馬兜鈴酸(aristolochic acid II)的混合劑，十八隻實驗鼠共分三組，每組各六隻（第一組餵食正常基礎飲食，第二組及第三組分別接受以胃管餵食5毫克/公斤/天及10毫克/公斤/天，每週餵5天，共餵食12週。實驗結果發現老鼠膀胱上皮隨著馬兜鈴酸的濃度上升有逐漸增生(proliferation)的現象，但是沒有惡性腫瘤的發生。Immunoprecipitation發現週期素D1/週期素依賴性激酶4複合物(cyclin D1/cdk 4)上升（第二組及第三組分別上升1.57及1.95倍）及週期素E/週期素依賴性激酶2複合物(cyclin E/cdk 2)上升（第二組及第三組分別上升1.46及1.62倍），進而促使Rb蛋白磷酸化（第二組及第三組分別上升1.75及2.07倍），最後造成Rb/E2F複合體的減少（第二組及第三組分別減至0.65及0.24倍），老鼠實驗發現馬兜鈴酸誘發老鼠泌尿上皮增生是經由週期素D1/週期素依賴性激酶4複合物(cyclin D1/cdk4)及週期素E/週期素依賴性激酶2複合物(cyclin E/cdk2)的活化。而後我們進行一個SV-HUC-1細胞與馬兜鈴酸混合液培養的研究。SV-HUC-1細胞培養於濃度分別為0.0125-0.2 毫莫耳的馬兜鈴酸混合液，分別於1、3、5天後測量細胞生存力，結果顯示SV-HUC-1 細胞之成長隨著馬兜鈴酸濃度增加(concentration-dependent)而受抑制。流式細胞儀(flow cytometry)顯示細胞週期分佈堆積在G0期/G1期 (從37.6% 增加到49.2%)。細胞週期之調控蛋白: p53、p21 和p27 的表達隨著馬兜鈴酸濃度增加(concentration-dependent)而增加。Immunoprecipitation 顯示出週期素E/週期素依賴性激酶2複合體(cyclin E/cdk 2)形成減少，但週期素D1/週期素依賴性激酶4複合體(cyclin D1/cdk 4)並沒有變化，導致週期素依賴性激酶2 (cdk 2)的自由態增加。另外，phospho-Rb的表達減少， Rb/E2F-1複合體增加，造成E2F因子釋放減少，因而抑制細胞增殖。前述現象是否與馬兜鈴酸導致的人類泌尿上皮癌有關，需要進一步研究釐清。
第二部份
數十年來，新移植藥物不斷推陳出新﹔睦體康腸衣錠(mycophenolate sodium) 的發明是為了要改善傳統山喜多(mycophenolate mofetil)的腸胃道副作用，而在其藥物的表面加上腸衣塗層; 我們使用睦體康治療經驗顯示: 腎臟移植術後第一年使用睦體康腸衣錠、環孢靈素(Cyclosporine)和類固醇等免疫抑制劑可維護移植腎臟功能穩定，對於腸胃道不適應病人，睦體康腸衣錠和山喜多的副作用其實相當，且可以互相替代。斥消靈(Sirolimus)亦是新一代的免疫抑制劑，其優點是可避免傳統免疫抑制劑如環孢靈素和普樂可復(tacrolimus; FK506)可能引起的慢性移植腎纖維化，我們使用斥消靈的經驗認為:斥消靈對於移植腎同時合併急性排斥和calcineurin 抑制劑毒性的治療是有益且有效的。
免疫抑制與感染則為一體兩面: 當免疫狀態過度被抑制可能引起受腎者得到感染，在器官移植患者的感染中，巨細胞病毒感染症的角色是很重要的，由於巨細胞病毒感染症的臨床表現相當多樣，我們報導三位以文獻上少見的臨床症狀來表現的巨細胞病毒感染症病患，這個治療經驗促使我們進行一項巨細胞病毒發燒篩檢，此發燒篩檢策略大大提昇巨細胞病毒感染症的治療效果。

Parallel Abstract 〈TOP〉

part 1
Aristolochic acid (AA) has been implicated in urothelial carcinoma in humans. To evaluate the effects of AA on the urinary bladder of rats, a histopathological study of three-month intragastric feeding with mixture of AA (41% AA I, 56% AA II) was carried out. A total of 18 experimental rats were divided into three feeding regimens, with six rats in each group (group I, normal basal diet; groups II and III received intragastric 5 mg and 10 mg isolated AA mixture/kg/day for 5 days/week for 12 weeks. Dosage-dependent urothelial proliferation, but not carcinoma, was found in the urothelium of the bladder of the rats administered with AA mixture. Immunoprecipitation showed elevations of cyclin D1/cdk 4 (increased induction by 1.57- and 1.95-fold in the groups II and III) and/or cyclin E/cdk 2 complex (increased induction by 1.46- and 1.62-fold in the groups II and III), which promote the increasing phosphorylation of Rb (increased induction by 1.75- and 2.07-fold in the groups II and III) and result in decrease of the Rb/E2F complex (decreased expression by 0.65- and 0.24-fold in the groups II and III). Our results provide evidence to suggest that exposure to AA results in urothelial proliferation in rats through cell cycle progression via activation of cyclin D1/cdk4 and cyclin E/cdk2. To evaluate the impact of AA on the human urinary tract epithelium cells, a study of SV-HUC-1 cells cultured with mixture of AA (AAM; 41% AA I, 56% AA II) was conducted. Cell viability was assayed in cultures exposed to 0.0125-0.2 mM AAM for 1, 3, and 5 days, a concentration-dependent inhibition on the growth of SV-HUC-1 cells was demonstrated. Cell cycle distribution determined by flow cytometry revealed an accumulation of cells in the G0/G1-phase (from 37.6% to 49.2%). The levels of p53, p21 and p27 increased in a concentration-dependent manner. Immunoprecipitation demonstrated a decrease in the formation of cyclin E/cdk 2 complex, but not cyclin D1/cdk 4 complex, which leads to an increase in the free form of cdk 2. Additionally, a decrease in the phospho-Rb correlates with an increase in Rb/E2F-1 complex which prevents the release of E2F transcription factor, thus preventing the transcription of the genes required for cell proliferation. Our results provide evidence that AAM induce cell cycle arrest in SV-HUC-1 cells. Whether these results are associated with AA-related human urothelial carcinoma requires further study to clarify.

Part 2.
Enteric-coated mycophenolate sodium (EC-MPS) is an enteric coated formulation delivering mycophenolic acid. The development of enteric coating was to improve the upper GI tolerability. Our experiences demonstrated that immunosuppression with EC-MPS, CsA and steroids maintained stable graft function among de novo kidney transplants. The adverse effects of EC-MPS and mycophenolate mofetil are comparable and they can be alternatively used in patients with GI intolerance.
Sirolimus, a potent non-nephrotoxic macrolide antibiotic, is also a newer immunosuppressant. Our experience found that sirolimus addition is beneficial and effective for acute allograft rejection accompained by simultaneous calcineurin inhibitor (CNI) toxicity.
Cytomegalovirus (CMV) infection is a common infectious complication following organ transplantation. We report a series of three kidney transplant recipients with rare presentations of CMV infections. Following treatment for these patients, we conducted a routine CMV PCR survey for all febrile patients within 6 months following transplantation. This implementation improves the diagnostic power and patient outcome in the CMV-infected kidney transplant recipients.

Reference ( 135 ) 〈TOP〉

Adams, P.D., 2001. Regulation of the retinoblastoma tumor suppressor protein by cyclin/cdks. Biochimica et biophysica acta. 1471, M123–M133.
連結：
Agarwal, R., 2000. Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention by dietary agents. Biochemical pharmacology. 60, 1051–1059.
連結：
Arai, T., Watanabe, J., Kawaguchi, M., Kamata, Y., Nishimura, Y., Jobo, T., Kuramoto, H, 2006. Clear cell adenocarcinoma of the endometrium is a biologically distinct entity from endometrioid adenocarcinoma. International journal of gynecological cancer. 16, 391-395.
連結：
Arlt, V.M., Schmeiser, H.H., Pfeifer, G.P., 2001. Sequence-specific detection of aristolochic acid-DNA adducts in the human p53 gene by terminal transferase-dependent PCR. Carcinogenesis 22:133-140.
連結：
Arlt, V.M., Stiborova, M., Schmeiser, H.H., 2002. Aristolochic acid as a probable human cancer hazard in herbal remedies. Mutagenesis 17:265-277.
連結：

Altmetrics

〈TOP〉

E-mail ：

When an article is available to download, a notice will be sent to your mailbox address.

E-mail ：