發(fā)布時間：2018-06-08 07:11

  本文選題：5-氟尿嘧啶 + 氟尿嘧啶植入劑　； 參考：《西南醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:食管癌是發(fā)病率較高的常見惡性腫瘤,在惡性腫瘤的死亡原因中排在前列,氟尿嘧啶作為消化道惡性腫瘤化療的傳統(tǒng)經(jīng)典藥物,在消化道惡性腫瘤的治療中發(fā)揮重要作用。本實驗為進一步探討抗腫瘤藥物5-氟尿嘧啶(5-Fu)類藥物在食管癌治療中的應(yīng)用潛力,我們通過體外實驗設(shè)計驗證了5-氟尿嘧啶及氟尿嘧啶植入劑對人食管癌TE-1細胞株生長的殺傷作用和誘導(dǎo)凋亡的能力,探尋有效的誘導(dǎo)腫瘤細胞凋亡的濃度和作用時間,為臨床制定合理的化療方案提供實驗室依據(jù)。通過臨床應(yīng)用研究進一步驗證了氟尿嘧啶植入劑治療食管癌的安全性及有效性。方法:第一部分:以體外培養(yǎng)的人食管癌TE-1細胞株為實驗研究對象,分別用5-氟尿嘧啶和氟尿嘧啶植入劑作用于TE-1,分別在不同時間點進行細胞計數(shù),找出凋亡明顯的藥物濃度及作用時間,并利用細胞凋亡檢測試劑盒進一步檢測不同質(zhì)量濃度及不同時間5-氟尿嘧啶及氟尿嘧啶植入劑對TE-1細胞生長的影響,以期望篩選出最適合的藥物質(zhì)量濃度和作用時間。具體的實驗設(shè)計包括以下兩個方面,(1)5-氟尿嘧啶對TE-1細胞增殖的抑制作用:根據(jù)文獻數(shù)據(jù)和預(yù)實驗將5-氟尿嘧啶組設(shè)四個濃度組0μg/ml、10μg/ml、50μg/ml、100μg/ml,分別處理TE-1細胞24h、48h、72h、96h后進行細胞計數(shù),找出凋亡明顯的藥物濃度及作用時間,并且利用細胞凋亡檢測試劑盒進行凋亡檢測。(2)氟尿嘧啶植入劑對TE-1細胞增殖的抑制作用:用氟尿嘧啶為內(nèi)標物,利用高效液相色譜法(HPLC)檢測,繪制氟尿嘧啶標準曲線,測量不同時間氟尿嘧啶植入劑的釋放濃度,依次在24h、48h、72h、96h處理te-1細胞,找出凋亡明顯的藥物濃度及作用時間,并進行細胞的凋亡檢測。第二部分:收集本院住院患者中行氟尿嘧啶植入劑治療食管癌的病例,在內(nèi)鏡直視下,將病灶以1.0cm的層間距分為若干層,每層內(nèi)以每間隔1.0cm種植一枚緩釋化療粒子;植入時每點植入10mg,依病情需要,每4周植入1次,種植3次為1個療程。此項研究中全部病患均順利完成治療。通過比對研究病患在治療前、治療后3個月及治療后6個月的臨床癥狀緩解情況、病灶面積變化情況、吞咽困難改善情況、不良反應(yīng)、生活質(zhì)量等。結(jié)果:(1)5-氟尿嘧啶對人食管癌細胞株te-1細胞周期的抑制與藥物處理的時間具有很強的相關(guān)性,在濃度為10μg/ml時對te-1作用明顯,增加藥物濃度并不能夠明顯地增加藥物作用的效果,且作用96小時時開始產(chǎn)生明顯差異,但進行凋亡檢測未見明顯的凋亡細胞。(2)使用高效液相色譜(hplc)測定氟尿嘧啶植入劑釋放量,發(fā)現(xiàn)緩釋化療粒子釋放的藥物濃度隨著時間的延長逐漸增加,到了48h以后基本維持平衡了,而且后面的濃度反而有點下降,氟尿嘧啶植入劑處理te-1細胞,發(fā)現(xiàn)不同時間有不同作用影響,當48h-72h時間段細胞數(shù)減少的最明顯,作用濃度約為282μg/ml,96小時內(nèi)作用時間越長作用越明顯,并且能夠明顯地檢測到凋亡細胞(3)治療前分別與治療3、6個月比較,患者病變面積、吞咽困難分級變化差異有統(tǒng)計學(xué)意義(p0.05);但生活質(zhì)量改善情況差異無統(tǒng)計學(xué)意義(p0.05,原因可能是隨訪時間較短及樣本量較少,未體現(xiàn)出個體之間差異);另外治療前與治療3個月白細胞(wbc)差異有統(tǒng)計學(xué)意義(p0.05);治療前、治療3和6個月并發(fā)癥情況發(fā)生率差異無統(tǒng)計學(xué)意義。結(jié)論:1.氟尿嘧啶注射液及氟尿嘧啶植入劑對人食管癌細胞株均有抑制其增殖的作用。2.氟尿嘧啶植入劑釋放濃度穩(wěn)定,有能促進人食管癌細胞株TE-1凋亡的作用,且96小時內(nèi)時間越長作用越明顯。3.氟尿嘧啶植入劑對食管癌細胞株的抑制效果優(yōu)于氟尿嘧啶注射液。4.內(nèi)鏡下植入5-氟尿嘧啶(5-FU)緩釋粒子治療晚期食管癌,是一種安全有效、毒副作用小、耐受性好的姑息治療方法。
[Abstract]:Objective: esophageal cancer is a common malignant tumor with high incidence of malignant tumor, and it is the leading cause of the death of malignant tumors. Fluorouracil plays an important role in the treatment of digestive malignant tumors. This experiment is a further study of the antitumor drug 5- fluorouracil (5-Fu). In the treatment of esophageal cancer, we verified the killing and apoptosis ability of 5- fluorouracil and Fluorouracil Implants on the growth of human esophageal cancer TE-1 cell lines by experimental design in vitro, to explore the effective induction of the concentration and time of the apoptosis of tumor cells, and to provide an experiment for the clinical formulation of a rational chemotherapy scheme. The safety and effectiveness of Fluorouracil Implants for the treatment of esophageal cancer was further verified by clinical application. Methods: Part 1: the TE-1 cell line of human esophageal cancer cells cultured in vitro was used as the experimental object, and 5- fluorouracil and Fluorouracil Implants were used for TE-1 respectively, and the cell count at different time points was carried out respectively. To find out the obvious drug concentration and action time of apoptosis, and to further detect the effect of 5- fluorouracil and Fluorouracil Implants on the growth of TE-1 cells at different mass concentration and different time by cell apoptosis detection kit, in order to screen out the most suitable drug quality concentration and time. Specific experimental designs include The next two aspects, (1) the inhibitory effect of 5- fluorouracil on the proliferation of TE-1 cells: according to the literature data and pre experiment, four concentration groups of 5- fluorouracil group were set up 0 mu g/ml, 10 mu g/ml, 50 mu g/ml, 100 mu g/ml, respectively, to deal with TE-1 cell 24h, 48h, 72h, after 96h, the cell count was carried out to find apoptotic drug concentration and action time, and the use of cells, and the use of cells Apoptosis detection kit for apoptosis detection. (2) the inhibitory effect of Fluorouracil Implants on the proliferation of TE-1 cells: using fluorouracil as the internal standard, using high performance liquid chromatography (HPLC) detection, draw the standard curve of fluorouracil, measure the release concentration of Fluorouracil Implants at different time, and in sequence in 24h, 48h, 72h, 96h to treat TE-1 cells. The concentration and time of the apoptotic drugs and the time of action were detected and the cell apoptosis was detected. The second part: collect the cases of the treatment of esophageal cancer by Fluorouracil Implants in the hospitalized patients in our hospital. Under the direct vision of the endoscopy, the focus is divided into several layers with the interval of 1.0cm in each layer, and one sustained release chemotherapy particle is planted at each interval in 1.0cm. 10mg was implanted at the point of disease, implanted 1 times every 4 weeks and 3 times for 1 courses. All patients were successfully treated in this study. The clinical symptoms remission of the patients before treatment, 3 months after treatment, 3 months after treatment and 6 months after treatment, the change of the lesion area, the improvement of dysphagia, adverse reactions, quality of life, etc. Results: (1) the inhibitory effect of 5- fluorouracil on the cell cycle of human esophageal cancer cell line TE-1 was strongly correlated with the time of drug treatment. The effect on TE-1 was obvious when the concentration was 10 g/ml. The increase of drug concentration could not significantly increase the effect of the drug effect, and the effect of the drug was obviously different when the effect was 96 hours, but the apoptosis was detected. No obvious apoptotic cells were found. (2) the release of Fluorouracil Implants was measured by high performance liquid chromatography (HPLC). It was found that the concentration of the drug released by the slow-release chemotherapy particles increased gradually with the prolongation of the time. After the 48h, the concentration of the drug was basically maintained, and the following concentration decreased slightly. The Fluorouracil Implants treatment of TE-1 cells was found. Different time has different effects. When the number of cells in 48h-72h time section decreases most obviously, the action concentration is about 282 mu g/ml, the longer the action time is more obvious in 96 hours, and it can be clearly detected before the treatment of apoptotic cells (3), compared with the treatment 3,6 months, the difference of the changes of the lesion area and dysphagia classification of the patients is statistically significant. There was no significant difference in the quality of life (P0.05), but there was no significant difference in the quality of life (P0.05, the reason may be that the follow-up time was shorter and the sample was less, not the individual difference), and the difference between the 3 months of white blood cells (WBC) before treatment was statistically significant (P0.05); before treatment, the incidence of complications in the treatment of 3 and 6 months was not unified. Conclusion: 1. Fluorouracil Injection and Fluorouracil Implants can inhibit the proliferation of human esophageal cancer cell lines. The release of.2. Fluorouracil Implants is stable and can promote the apoptosis of human esophageal cancer cell line TE-1, and the longer the time within 96 hours the more obvious the.3. Fluorouracil Implants is fine for esophageal cancer. The inhibitory effect of the cell line is better than that of the Fluorouracil Injection.4. endoscopy with 5- fluorouracil (5-FU) sustained-release particles for the treatment of advanced esophageal cancer. It is a safe, effective, less toxic side effect and a tolerable palliative treatment.
【學(xué)位授予單位】：西南醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.1

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本文編號：1995066