兰州大学机构库 >学院待认领
丙戊酸镁抑制膀胱移行细胞癌的临床研究
Alternative TitleMagnesium valproate inhibits transitional cell carcinoma of the bladder:a clinical study
王一辰
Thesis Advisor王志平
2010-05-27
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name博士
Keyword丙戊酸 膀胱肿瘤 乙酰化 血管内皮生长因子 凋亡指数
Abstract目的:本研究的目的是在临床上探索丙戊酸镁抑制膀胱肿瘤的安全性和有效性。 方法:纳入24例膀胱癌的患者,分为两组(每组12例),分别给予口服丙戊酸镁20mg/kg•d或30mg/kg•d,连续治疗10天。我们用检测三种抗肿瘤指标并观察丙戊酸镁治疗的副作用。 结果:20mg/kg和 30mg/kg两组的平均日剂量分别是1220, 1890 mg。丙戊酸的血清浓度波动在77.4–137.3 µg/mL之间,平均值是106.5 µg/mL。最常引起患者不适的是嗜睡和疲乏,没有严重的毒副作用发生。我们的研究显示用丙戊酸镁治疗(不分剂量水平)后的膀胱肿瘤组织H3组蛋白乙酰化水平高于未用丙戊酸镁治疗的对照组(p=0.001),尤其是在浸润性膀胱癌更加明显(p <0.001)。在30mg/kg剂量下,观察到用药后肿瘤组织的H3组蛋白乙酰化水平高于未用药的对照组(p=0.001)。在浅表性膀胱癌的13例患者中,有2例出现VEGF表达的抑制。在浸润性膀胱癌的11例患者中,观察到有4例出现VEGF表达的抑制。同时发现,11例浸润性膀胱癌患者用药后的肿瘤组织凋亡指数明显高于用药前(p=0.008), 6例丙戊酸镁服用剂量为30mg/kg•d患者的肿瘤组织凋亡指数较服药前增高(p<0.05)。 结论:丙戊酸镁在30 mg/kg•d剂量水平治疗膀胱肿瘤,具有H3组蛋白乙酰化作用,而且有抑制VEGF的表达、诱导肿瘤组织凋亡的作用。
Other AbstractBackground: Histone acetylation as an epigenetic change is widely studied in cancer. Valproate acid, a histone deacetylases inhibitor, has been verificated to have anticancer effects in many studies. The purpose of this study is to explore the efficacy and safety of magnesium valproate treatment to bladder tumor. Methods: Twenty-four patients diagnosed with bladder tumor were administered magnesium valproate at 20mg/kg•d or 30mg/kg•d dose level(12 patients each,randomly) via oral route for 10 days before conventional surgical intervention. The tumor tissues and blood sample from baseline and posttreatment were collected. The anticancer activity including tumor acetylation of H3 histones by detecting OD value (between magnesium valproate treatment group and control group), inhibition of VEGF expression by immunohistochemistry and induction of apoptosis by TUNEL (between baseline tumor biopsies and surgical tumor tissues)were evaluated according to the study protocol. Blood serum VPA concentrations were measured in all 24 patients. Besides, side effects of treatment were observed. ResuLts: All patients received the medication without dosage adjustment. The mean daily dose for the doses 20-and 30-mg/kg were 1220, 1890 mg, respectively. Serum levels of valproic acid ranged from 77.4–137.3 µg/mL, for a overall mean of 106.5 µg/mL, and corresponding average blood levels for the two doses were 96.51, 116.53 µg/mL. The most frequent complaints were moderate somnolence (3 patients) and slight fatigue (4 patients), but no severe toxicity was reported. Our study showed H3 histone acetylation level in tumors after magnesium valproate treatment (regardless of dose level) is higher than that of control group(p=0.001), especially for invasive bladder tumor (p<0.001). At 30-mg/kg dose level,histone H3 acetylation in tumors after magnesium valproate treatment is higher than that of control group (p=0.001). Whereas, the difference was no statistically significant between 20-mg/kg dose level magnesium valproate treatment group and control group (p=0.098). There were inhibition of VEGF expression for invasive bladder tumor, in 4 of 11patients (36.4%), and 3 of the four cases belonged to the 30 mg/kg dose level. Besides, for 11 patients with invasive bladder tumor, the apoptotic index mean of post-treatment samples was significantly higher than that of pre-treatment samples (p=0.008). Six cases treated by 30mg/kg•d magnesium valpro...
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/223806
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
王一辰. 丙戊酸镁抑制膀胱移行细胞癌的临床研究[D]. 兰州. 兰州大学,2010.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Altmetrics Score
Google Scholar
Similar articles in Google Scholar
[王一辰]'s Articles
Baidu academic
Similar articles in Baidu academic
[王一辰]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[王一辰]'s Articles
Terms of Use
No data!
Social Bookmark/Share
No comment.
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.