本文選題：肝細(xì)胞癌 + 微血管密度　； 參考：《大連醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的:超聲觀察肝癌血流分級(jí)及其血流情況，并探討缺氧誘導(dǎo)因子-1α(hypoxiainducible factor-1alpha，HIF-1α)與微血管密度(microvessel density，MVD)在肝癌組織中的表達(dá)及二者間關(guān)系。 方法:對(duì)60例經(jīng)病理證實(shí)的原發(fā)性肝癌手術(shù)切除術(shù)前進(jìn)行二維及彩色多普勒超聲檢查，進(jìn)行血流分級(jí)，通過(guò)免疫組織化學(xué)的方法檢測(cè)HIF-1α、MVD在肝癌組織中的表達(dá)。 結(jié)果:肝癌超聲血流分級(jí)為I級(jí)時(shí)HIF-1a、MVD表達(dá)率分別為（64.37±3.02）、（39.32±3.71），血流分級(jí)為II級(jí)時(shí)HIF-1a、MVD表達(dá)率分別為（79.94±2.97）、（62.25±3.80），血流分級(jí)為III級(jí)時(shí)HIF-1a、MVD表達(dá)率分別為（92.61±3.10）、（85.16±2.33），超聲肝癌血流等級(jí)和HIF-1α、MVD相關(guān)，在肝癌組織中當(dāng)血流分級(jí)為III級(jí)時(shí)HIF-1a、MVD表達(dá)率最高，分別為92.61%±3.10、85.16%±2.33，在正常肝組織中HIF-1a、MVD表達(dá)率分別為12.28%±7.21、11.33%±7.21，二者比較具有顯著性差異(P0.05)。 結(jié)論: HIF-1a的表達(dá)與肝癌新生血管的生成密切相關(guān)，MVD高表達(dá)、HIF-1α表達(dá)越高，彩色多普勒顯示血流越豐富，肝癌超聲血流分級(jí)能夠?yàn)榕R床診治肝癌、評(píng)估療效提供理論依據(jù)。 目的:研究兔肝VX2瘤射頻消融治療（Radiofrequency Ablation，RFA）后殘癌中胰島素生長(zhǎng)因子-II（Insulin-like growth factor,IGF-II）、增殖細(xì)胞核抗原(proliferating cell nuclear antigen,PCNA)的表達(dá)。 方法:實(shí)驗(yàn)兔28只，3只VX2荷瘤兔。2只作為傳代兔，余23只實(shí)驗(yàn)兔行超聲引導(dǎo)下肝內(nèi)瘤塊植入，建立VX2肝癌模型。從荷瘤兔切取腫瘤周邊生長(zhǎng)旺盛的魚肉樣組織，隨機(jī)取2只實(shí)驗(yàn)兔，于雙腿內(nèi)側(cè)局麻后，手術(shù)刀破皮，用鑷子將瘤塊送入皮下，，傳代（傳代兔）。超聲引導(dǎo)下將VX2瘤粒分批接種于23只實(shí)驗(yàn)兔肝臟內(nèi)，制成肝癌模型。將實(shí)驗(yàn)兔隨機(jī)分為5組：對(duì)照組3只（A組），不行RFA治療；余下20只行超聲引導(dǎo)下RFA治療，射頻范圍為腫瘤最大半徑的2/3，人為造成腫瘤組織殘余。按治療后不同時(shí)間分為射頻后0h組（B組）5只；射頻后1w組（C組）5只；射頻后2w組（D組）5只；射頻后4w組（E組）5只。各組經(jīng)超聲檢查后將實(shí)驗(yàn)兔處死，切取標(biāo)本，采用免疫組織化學(xué)法觀察A組腫瘤及B-E組殘余腫瘤組織中IGF-II及PCNA的表達(dá)情況。 結(jié)果：1．造模結(jié)果:接種后2-4w行超聲檢查，23只實(shí)驗(yàn)兔均種植成功。超聲顯示肝臟種植區(qū)圓形或類圓形低回聲腫物，內(nèi)回聲均勻，大小1.5±0.5cm，邊界清，無(wú)包膜回聲，血流豐富。A組經(jīng)病理證實(shí)，接種成功率100%。 2．RFA術(shù)后超聲結(jié)果：術(shù)后0h腫瘤損毀區(qū)為不規(guī)則汽化強(qiáng)回聲，邊界不清，形態(tài)不規(guī)則，彩色多普勒（CDF）及能量多普勒（CDE）:無(wú)法測(cè)到血流信號(hào)。術(shù)后1w、2w、4w腫瘤大小與術(shù)前相似，治療區(qū)呈不規(guī)則高回聲，中心區(qū)可見少量不規(guī)則無(wú)回聲；術(shù)后1w、2w CDF及CDE無(wú)明顯血流信號(hào)，術(shù)后4w CDE部分殘癌周圍可見血流信號(hào)。 3．HE染色結(jié)果：A組瘤體及B-E組殘癌細(xì)胞核大深染，異型性明顯，呈巢狀分布。射頻區(qū)凝固壞死，可見核固縮、核碎裂、核溶解，周圍見大量紅染組織，淋巴細(xì)胞浸潤(rùn)，周圍形成1-3mm炎癥反應(yīng)帶；射頻1w后開始出現(xiàn)液化，2w液化壞死范圍擴(kuò)大，炎癥反應(yīng)帶纖維化。 4．免疫組織化學(xué)結(jié)果：A組IGF-II、PCNA呈高表達(dá)，分別為（86.3±12.5）、（65.37±13.36）；B組IGF-II、PCNA在殘癌組織中表達(dá)陽(yáng)性率為（78.9±13.3）、（50.78±13.98）；C組IGF-II、PCNA在殘癌組織中表達(dá)陽(yáng)性率為（47.2±10.2）、（35.63±10.20）；D組IGF-II、PCNA在殘癌組織中表達(dá)陽(yáng)性率為（18.9±4.3）、（17.80±5.17）；E組IGF-II、PCNA在殘癌組織中表達(dá)陽(yáng)性率為（10.6±1.89）、（9.91±1.63）。B-E組IGF-II、PCNA在消融區(qū)均低表達(dá)。 結(jié)論:射頻消融治療可使兔肝VX2腫瘤殘余組織中癌細(xì)胞失去活性，從而起到進(jìn)一步的治療作用。
[Abstract]:Objective: To observe the blood flow classification and blood flow of liver cancer, and to explore the relationship between the expression of hypoxia inducible factor -1 alpha (hypoxiainducible factor-1alpha, HIF-1 a) and microvascular density (microvessel density, MVD) in the liver cancer tissues and the relationship between the two.
Methods: 60 cases of primary liver cancer confirmed by pathology were examined by two-dimensional and color Doppler ultrasonography before operation, and the blood flow classification was carried out. The expression of HIF-1 alpha and MVD in liver cancer tissues was detected by immunohistochemistry.
Results: the ultrasound blood flow classification of liver cancer was I grade HIF-1a, MVD expression rate was (64.37 + 3.02), (39.32 + 3.71), blood flow classification was II grade HIF-1a, MVD expression rate was (79.94 + 2.97), (62.25 + 3.80), III grade HIF-1a, MVD expression rate was (92.61 + 3.10), (85.16 + 2.33), HIF-1 alpha, MVD phase of ultrasonic liver cancer When the blood flow classification was III grade, the expression rate of MVD was the highest, which was 92.61% + 3.10,85.16% + 2.33 respectively. The expression rate of HIF-1a and MVD in normal liver tissues was 12.28% + 7.21,11.33% + 7.21 respectively. The two groups had significant difference (P0.05).
Conclusion: the expression of HIF-1a is closely related to the formation of neovascularization of liver cancer. The higher expression of MVD, the higher the expression of HIF-1 a, the more rich the color Doppler shows, the ultrasound flow classification of liver cancer can provide a theoretical basis for the clinical diagnosis and treatment of liver cancer.
Objective: To study the expression of insulin growth factor -II (Insulin-like growth factor, IGF-II) and proliferating cell nuclear antigen (proliferating cell nuclear) in the residual cancer of rabbit liver VX2 tumor (Radiofrequency Ablation, RFA).
Methods: 28 rabbits and 3 rabbits with VX2 tumor bearing only were used as passage rabbits, and the remaining 23 rabbits were implanted with intrahepatic tumors under ultrasound guidance to establish a VX2 liver cancer model. The tumor tissue surrounding the tumor was harvested from the tumor rabbit. 2 rabbits were taken randomly from the tumor rabbits. After local anesthesia, the scalpel broke the skin, and the tumor block was sent to the subcutaneous and passages with tweezers. Under the guidance of ultrasonic guidance, the VX2 tumor particles were inoculated into 23 experimental rabbits' liver and made into a liver cancer model. The experimental rabbits were randomly divided into 5 groups: 3 control group (group A) and no RFA treatment; the remaining 20 were treated by ultrasound guided RFA, the range of radiofrequency was 2/3 of the maximum radius of the tumor. 5 rats were divided into group 0h (group B) after radiofrequency, 5 in group 1W (group C) after radiofrequency, 5 in group 2W (group D) after radiofrequency, 5 in group 4W (group E) after radiofrequency. After ultrasound examination, the rabbits were killed and specimens were cut and specimens were cut, and the expression of IGF-II and PCNA in group A tumor and B-E group was observed by immunohistochemistry.
Results: 1. the results were as follows: 2-4w ultrasound examination after inoculation, 23 rabbits were planted successfully. Ultrasound showed round or circular hypoechoic tumor in the liver planting area. The internal echo was uniform, the size was 1.5 + 0.5cm, the boundary was clear, no envelope echo, the blood flow rich.A group was confirmed by pathology, and the success rate of grafting was 100%.
2.RFA postoperative ultrasound results: postoperative 0h tumor damaged area was irregular vaporized strong echo, irregular boundary, irregular shape, color Doppler (CDF) and energy Doppler (CDE): no blood flow signal was detected. Postoperative 1W, 2W, 4W tumor size was similar to preoperative, irregular hyperechoic in the treatment area, and a small amount of irregular anechoic in the center area; 1 after operation. W, 2W CDF and CDE had no obvious blood flow signals. Blood flow signals were found around 4W CDE partial residual tumor after operation.
3.HE staining results: the cell nuclei of tumor body and group B-E in group A were deeply dyed, with obvious heteromorphosis and nesting distribution. The radiofrequency region solidified and necrotic, visible nuclear condensation, nuclear fragmentation, nuclear disintegration, a large number of red dyed tissues, lymphocytic infiltration, and peripheral formation of 1-3mm inflammatory zone; 1W began to liquefy after 1W, and 2W liquefaction necrosis expanded, inflammation expanded. The disease reacts with fibrosis.
4. immunohistochemical results: A group IGF-II, PCNA showed high expression, respectively (86.3 + 12.5), (65.37 + 13.36), IGF-II, PCNA in the B group was (78.9 + 13.3), (50.78 + 13.98), C group IGF-II, PCNA in the residual cancer tissues (47.2 + 10.2), (35.63 + 10.20), D IGF-II, PCNA in the residual cancer tissue expression. The positive rate was (18.9 + 4.3), (17.80 + 5.17), and the positive rate of IGF-II in E group was (10.6 + 1.89), (9.91 + 1.63).B-E group IGF-II, and PCNA was low expression in the ablation area.
Conclusion: radiofrequency ablation can make the cancer cells lose their activity in the remnant tissues of VX2 tumor of rabbit liver, thereby playing a further therapeutic role.

【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R445.1;R735.7

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