3.0T MR弥散成像评价光动力治疗QBC939胆管癌荷瘤裸鼠疗效及病理相关研究

发布时间：2018-06-03 20:07

  本文选题：光动力 + 裸鼠QBC939胆管癌皮下移植瘤模型　； 参考：《大连医科大学》2017年硕士论文

【摘要】：研究背景和目的:肝脏胆管细胞癌(cholangiocarcinoma,CC)恶性程度高、侵袭性强、发病隐匿、是我国胆道系统常见的、死亡率较高的恶性肿瘤之一。根治性切除术是治愈胆管癌的唯一手段,然而临床上可以进行根治性切除的患者低于10%。光动力(photodynamic therapy PDT)在国外是一种比较成熟的胆管癌治疗手段,而在我国临床上应用金丝桃素作为光敏剂进行胆管癌局部治疗还相对较少。胆管癌恶性程度高,肿瘤血管生成、细胞增殖是病变进展的重要生物学行为,直接决定其恶性程度。本课题以人QBC939胆管癌皮下荷瘤裸鼠模型为基础,利用金丝桃素作为光敏剂进行光动力治疗,利用磁共振平扫T1WIT2WI、弥散加权成像(DWI)对光动力治疗QBC939胆管癌裸鼠模型疗效进行评估,将MVD、Ki67检测结果进行对比,探讨利用MR-DWI检查在评估光动力在治疗人QBC939胆管癌皮下荷瘤裸鼠模型疗效方面的应用价值、浅谈金丝桃素PDT治疗QBC939胆管癌的机制,观察以金丝桃素作为光敏剂进行PDT治疗的近期疗效,从而为3.0TMRI评估光动力治疗胆管癌疗效提供重要临床依据。材料与方法:利用人QBC939胆管癌细胞株建立30只皮下移植瘤裸鼠模型,并将其平均分为A(对照组)、B(金丝桃素PDT组)两组,处理前后进行MRI和DWI扫描,MR序列包括轴位、矢状位、冠状位tirmT2WI序列、轴位、矢状位dark-fluid T1WI序列。DWI检查采用diff-mddw序列行轴位DWI扫描,激励次数(NXE)=1,b值分别为:0/mm2-300s/mm2,0/mm2-700s/mm2,得到两组 b 值下 A、B 两组处理前后人 QBC939胆管癌裸鼠皮下移植瘤模型肿瘤病灶的DWI图及相应ADC图,筛选出最佳ADC图,测量ADC值。A、B两组分别注射胜生理盐水、金丝桃素,然后进行光照处理,A组实验鼠在完成第二次影像学检查后同B组一起处死,两组荷瘤裸鼠病灶进行常规HE染色切片,并进行免疫组化CD34染色计数微血管密度MVD和Ki67染色。结果:QBC939胆管癌病灶ADC值与Ki67呈负相关,P0.05结果具有统计学意义;与MVD相关性较差,P0.05结果不具有统计学意义;治疗后急性期内治疗组B组肿瘤体积为(3.11±0.78)cm3小于A组对照组体积(1.83±0.38)cm3。利用金丝桃素光动力治疗后B组胆管癌组织ADC值(985.39±36.99)×10-6mm2较A组ADC值(811.94±34.89)×10-6mm2明显升高;KI67降低,差异具有统计学意义(P0.05)。结论:利用3.0T MRI 4通道正交动物线圈得到不同序列(T1WIT2WI和DWI)可以清晰显示荷瘤鼠肿瘤组织形态、内部信号、周围组织局部受侵情况;ADC值与肿瘤Ki67有着良好相关性,可以在细胞水平上反映光动力治疗后人QBC939胆管癌裸鼠皮下移植瘤模型的肿瘤实性部分细胞增殖受限程度;DWI显示光动力治疗在体胆管癌具有良好的疗效,可以为光动力治疗胆管癌的临床应用提供重要帮助。
[Abstract]:Background and objective: cholangiocarcinoma (CC) is highly malignant, aggressive and occult. It is one of the most common and high mortality malignant tumors in China's biliary tract. Radical resection is the only cure for cholangiocarcinoma. However, patients undergoing radical resection on the bed are less than 10%. photodynamic ( Photodynamic therapy PDT) is a relatively mature treatment for cholangiocarcinoma abroad. However, the clinical application of hypericin as a photosensitizer for local treatment of cholangiocarcinoma is relatively small. The malignant degree of the bile duct cancer is high, the tumor angiogenesis, cell proliferation is an important biological behavior of the disease, which directly determines its malignant process. On the basis of the nude mice model of human QBC939 cholangiocarcinoma subcutaneous tumor, we use hypericin as photosensitizer to carry out photodynamic therapy, use magnetic resonance (MRI) T1WIT2WI, diffusion weighted imaging (DWI) to evaluate the effect of photodynamic treatment of nude mice model of QBC939 cholangiocarcinoma, compare the results of MVD, Ki67 detection, and explore the use of MR-DWI examination. To evaluate the application value of photodynamic in the treatment of nude mice model of QBC939 cholangiocarcinoma subcutaneous tumor, and to discuss the mechanism of hypericin PDT in the treatment of QBC939 cholangiocarcinoma, and observe the short-term effect of hypericin as a photosensitizer for the treatment of PDT, so as to provide an important clinical basis for the evaluation of the therapeutic effect of 3.0TMRI on the therapeutic effect of photodynamic therapy on cholangiocarcinoma. Materials and methods: the human QBC939 cholangiocarcinoma cell line was used to establish 30 nude mice models of subcutaneous transplantation tumor. The average was divided into A (control group) and B (hypericin PDT group). MRI and DWI scan were performed before and after treatment. The MR sequence included axial, sagittal, coronal tirmT2WI sequence, axis and sagittal dark-fluid T1WI sequence.DWI examination of diff-mddw Sequence row axis DWI scan, excitation frequency (NXE) =1, b value respectively: 0/mm2-300s/mm2,0/mm2-700s/mm2, obtained the DWI map and corresponding ADC map of the two groups of B values A, B two before and after treatment of the human QBC939 bile duct cancer nude mice subcutaneous tumor model. The best ADC diagram was screened, the two groups were injected with physiological saline and Hypericum respectively. The experimental mice in group A were executed with B after second times of imaging examination. The two groups of tumor bearing nude mice were stained with conventional HE staining and immunohistochemical CD34 staining was used to count the microvascular density MVD and Ki67 staining. The results showed that the ADC value of the QBC939 cholangiocarcinoma was negatively correlated with Ki67, and the P0.05 results were statistically significant. Significance; poor correlation with MVD, P0.05 results were not statistically significant; after treatment, the volume of tumor in group B was (3.11 + 0.78) cm3 less than that of group A (1.83 + 0.38) cm3. using hypericin (985.39 + 36.99) ADC (985.39 + 36.99) * 10-6mm2 (811.94 + 34.89) * 10-6mm2. The difference was statistically significant (P0.05). Conclusion: different sequences (T1WIT2WI and DWI) using the 3.0T MRI 4 channel orthogonal animal coils (T1WIT2WI and DWI) can clearly show the tumor tissue morphology, internal signal and local invasion of the surrounding tissues, and the ADC value has a good correlation with the tumor Ki67, which can reflect the light at the cell level. QBC939 cholangiocarcinoma in nude mice after dynamic treatment of nude mice with subcutaneous transplantation tumor model of tumor real part of cell proliferation limitation, DWI showed that photodynamic therapy has good therapeutic effect in body cholangiocarcinoma, and can provide important help for the clinical application of photodynamic treatment of cholangiocarcinoma.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.8;R445.2
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本文编号：1974016