本文選題：移植瘤 + 裸鼠��； 參考：《中國協(xié)和醫(yī)科大學(xué)》2010年博士論文

【摘要】： [背景]甲狀腺低分化癌和未分化癌是頭頸部腫瘤惡性程度最高的腫瘤,目前主要采用手術(shù)、放療和化療的綜合治療,由于病變發(fā)展迅速、遠處轉(zhuǎn)移比例高,總體治療效果差,由于發(fā)病率較低,較難開展大樣本的隨機對照研究,目前尚缺乏統(tǒng)一的治療規(guī)范和化療方案。局部復(fù)發(fā)和遠處轉(zhuǎn)移是主要致死原因,新的化療藥物尤其是分子靶向藥物的出現(xiàn),使研究者對化療在提高局部控制和降低遠處轉(zhuǎn)移兩方面的作用冀以新的希望,國外多個Ⅰ／Ⅱ期臨床研究正在進行,目前國內(nèi)尚無同類研究。 [目的]建立甲狀腺低分化和未分化癌的裸鼠移植瘤模型；評估脂質(zhì)體阿霉素、索拉非尼治療甲狀腺低分化癌移植瘤的療效；篩選對甲狀腺低分化和未分化癌細胞敏感的化療藥物,為臨床治療提供參考。 [方法]選取甲狀腺乳頭狀癌、低分化癌和未分化癌的手術(shù)標本進行裸鼠皮下接種,通過連續(xù)傳代建立穩(wěn)定的移植瘤模型；用脂質(zhì)體阿霉素(liposome doxorubicine)和索拉非尼(sorafenib, BAY 43-9006, Nexavar,多吉美)治療裸鼠甲狀腺低分化癌移植瘤,觀察腫瘤生長情況,評估兩種藥物的療效；分別利用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴鹽[3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT]及三磷酸腺苷腫瘤藥物敏感性檢測(adenosine triphosphate-tumor chemosensitivity assay, ATP-TCA)的方法對甲狀腺癌細胞進行體外藥物敏感性檢測,篩選敏感藥物。 [結(jié)果]3例甲狀腺低分化和未分化癌裸鼠移植瘤模型均成功建立并傳代,其中1例低分化癌模型連續(xù)傳代后生長穩(wěn)定,成瘤率達100%,而且腫瘤生長及信號傳導(dǎo)相關(guān)蛋白表達穩(wěn)定,適合進一步的動物實驗；3例甲狀腺乳頭狀癌移植瘤均未生長。利用脂質(zhì)體阿霉素和索拉非尼對甲狀腺低分化癌模型進行化療,效果較明顯,空白對照組、溶劑對照組、單藥脂阿組、索拉非尼組、低量聯(lián)合組、中量聯(lián)合組、高量聯(lián)合組化療結(jié)束后移植瘤的最終平均體積分別為1274.13±393.76mm3、1060.00±469.05mm3、726.76±488.22mm3、451.54±97.75mm3、518.37±164.44mm3、310.51±210.53mm3和228.44±129.21mm3,瘤重分別為1.13±0.42g、0.91±0.39g、0.78±0.45g、0.55±0.17g、0.52±0.19g、0.34±0.21g和0.19±0.09g,單藥脂阿組、索拉非尼組、低量聯(lián)合組、中量聯(lián)合組、高量聯(lián)合組的抑瘤率分別為30.8%、40.8%、42.3%、62.9%和72.6%,高量聯(lián)合組抑瘤率除與中量聯(lián)合組無差異外(P=0.357)均高于其余各組,中量聯(lián)合組優(yōu)于單藥脂阿組(P=0.001),而與索拉非尼組無差異(P=0.192)。各治療組平均瘤重均明顯低于空白對照組(P0.05)。各治療組均無實驗鼠死亡,高量聯(lián)合組實驗鼠體重在治療過程中較其余各治療組有明顯減輕(P0.05)。利用MTT法發(fā)現(xiàn)索拉非尼對甲狀腺乳頭狀癌、低分化和未分化癌均不同程度的敏感,而ATP-TCA方法則顯示對3例甲狀腺低分化和未分化癌均敏感的藥物是長春新堿(VCR)、吉西他濱(GEM)以及順鉑+紫杉醇(DDP+PTX)的聯(lián)合方案。 [結(jié)論]甲狀腺低分化癌和未分化癌較乳頭狀癌移植成瘤率高,移植瘤模型經(jīng)連續(xù)傳代后穩(wěn)定,適合動物藥效學(xué)等研究；脂質(zhì)體阿霉素和索拉非尼無論單藥還是聯(lián)合應(yīng)用對本例甲狀腺低分化癌移植瘤模型均有明顯的抑瘤作用,中量聯(lián)合療效明顯且副作用小。甲狀腺低分化和未分化癌細胞藥物敏感性個體差異較大,臨床治療前建議進行體外細胞藥敏檢測進行個體化的選擇,ATP-TCA可能是一種比較理想的檢測方法。
[Abstract]:background of the invention thyroid low differentiation cancer and undifferentiated carcinoma are the most malignant tumors in the head and neck , and the present invention mainly adopts the comprehensive treatment of surgery , radiotherapy and chemotherapy , and has the advantages of rapid lesion development , high distant metastasis ratio and poor overall treatment effect .



Objective To establish a model of nude mice transplantation tumor with low thyroid and undifferentiated carcinoma .
To evaluate the efficacy of liposomal doxorubicin and sorbiani in the treatment of low - differentiated thyroid carcinoma ;
Screening of chemotherapeutics sensitive to low thyroid and undifferentiated cancer cells provides a reference for clinical treatment .



Methods : The operation specimens of thyroid papillary carcinoma , low differentiation carcinoma and undifferentiated carcinoma were subcutaneously inoculated in nude mice , and stable transplanted tumor model was established by continuous passage .
To evaluate the effects of liposome doxorubescens and soralea , BAY 43 - 9006 , Nexavar , Dogius in the treatment of low - differentiated thyroid carcinoma in nude mice and to observe the growth of tumor and evaluate the efficacy of the two drugs .
The sensitivity of 3 - ( 4,5 - dimethylthiazol - 2 ) -2,5 - diphenyltetrazol - 3 - ( 4,5 - dimethylimidazol - 2 - yl ) -2,5 - diphenyltetrazol bromide ( MTT ) and adenosine triphosphate ( ATP - TCA ) was used to detect the drug sensitivity of thyroid cancer cells in vitro and to screen sensitive drugs .



Results Three cases of low differentiation and undifferentiated carcinoma of nude mice were successfully established and passaged . Among them , 1 case of low differentiation cancer model was stable after continuous passage , the rate of tumor formation reached 100 % , and tumor growth and signal transduction related protein expression was stable , which was suitable for further animal experiments ;
There was no difference between the two groups ( P = 0 . 05 ) . The tumor weight was significantly lower than that in the control group ( P = 0 . 05 ) . The tumor weight was 1 . 13 鹵 393.76 mm3 , 0 . 78 鹵 0 . 21 g , 0 . 91 鹵 0 . 19 g , 0 . 34 鹵 0 . 21 g and 0 . 19 鹵 0 . 09 g .



Conclusion Low differentiation and undifferentiated carcinoma of the thyroid gland have higher tumor rate than papillary carcinoma , and the transplanted tumor model is stable after continuous passage and is suitable for animal pharmacodynamics and other studies .
In the present case , the tumor model of low differentiation and undifferentiated carcinoma of the thyroid has obvious tumor inhibiting effect , and the combined effect of the liposome doxorubicin and sorbiani is obvious and the side effect is small . The sensitivity of the thyroid low differentiation and the undifferentiated cancer cell is small . The sensitivity of the thyroid low differentiation and the undifferentiated cancer cell is large , and the individual selection of the in vitro cell drug sensitivity detection is recommended before clinical treatment , and the ATP - TCA may be a comparatively ideal detection method .

【學(xué)位授予單位】：中國協(xié)和醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2010
【分類號】：R-332;R736.1

【參考文獻】

相關(guān)期刊論文 前10條

1 徐建明,宋三泰,湯仲明,江澤飛,劉曉晴,劉廣賢,周莉,張婧;人乳腺癌細胞MTT藥敏試驗評價標準的研究[J];癌癥;1999年03期

2 田海梅,李艷芬,吳健雄,曹冬艷,榮維淇,劉毅,李茉,王海鵬,王小兵,張偉;應(yīng)用ATP生物熒光腫瘤體外藥敏檢測技術(shù)研究大腸癌藥敏的異質(zhì)性[J];癌癥進展;2005年05期

3 孫輝,王金國,付言濤,張德恒;人甲狀腺未分化癌細胞裸鼠皮下移植模型的建立[J];吉林大學(xué)學(xué)報(醫(yī)學(xué)版);2003年04期

4 周平紅,秦新裕;脂質(zhì)體阿霉素及其靶向治療研究進展[J];中國臨床醫(yī)學(xué);2002年04期

5 陳衛(wèi)東,張弘煒,范健;脂質(zhì)體阿霉素對小鼠移植性腫瘤的治療作用[J];現(xiàn)代醫(yī)學(xué);2002年06期

6 馮影;高明;;94例甲狀腺未分化癌臨床分析[J];天津醫(yī)科大學(xué)學(xué)報;2008年02期

7 徐偉,梁美庚;頭頸部癌化療藥敏試驗研究[J];中華耳鼻咽喉科雜志;1996年04期

8 張偉;;生物熒光腫瘤體外藥敏檢測技術(shù)的臨床應(yīng)用[J];中華檢驗醫(yī)學(xué)雜志;2005年12期

9 田海梅,石曉燕,傅軍,曹冬艷,張凱,吳令英,王金萬,張偉;ATP抗腫瘤藥物敏感性檢測技術(shù)與卵巢癌臨床治療的相關(guān)性研究[J];中華腫瘤雜志;2005年05期

10 孫輝,王金國,張德恒,鄭澤霖;人甲狀腺未分化癌細胞系TA-K裸鼠原位移植模型的建立[J];中國普外基礎(chǔ)與臨床雜志;2002年05期

相關(guān)博士學(xué)位論文 前1條

1 解亦斌;胰腺癌肝轉(zhuǎn)移脂質(zhì)體阿霉素介入化療實驗研究[D];中國協(xié)和醫(yī)科大學(xué);2009年

，

本文編號：1752930