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照射時間延長對鼻咽癌放射生物學(xué)效應(yīng)的實(shí)驗(yàn)研究

發(fā)布時間:2018-05-12 07:00

  本文選題:放射治療 + 鼻咽癌CNE-2Z細(xì)胞。 參考:《天津醫(yī)科大學(xué)》2013年博士論文


【摘要】:第一部分照射時間延長對小鼠鼻咽癌CNE-2Z細(xì)胞殺滅作用的影響 目的模擬精確放療照射模式,觀察照射時間延長對小鼠鼻咽癌CNE-2Z細(xì)胞殺滅作用的影響及相關(guān)基因蛋白Bcl-2, Bax表達(dá)的變化。 方法荷鼻咽癌CNE-2Z細(xì)胞雄性小鼠隨機(jī)分成4個組,每組10只:假照組,常規(guī)照射組,IMRT模擬組,IGRT模擬組。小鼠用10%水合氯醛(350mg/kg,腹腔注射)麻醉后固定于平板上,利用瓦里安23-EX加速器進(jìn)行一次性腫瘤靶區(qū)照射,6MV-X線,照射野給于1cm厚組織補(bǔ)償,總劑量18Gy,劑量率6Gy/min。(1)常規(guī)照射組分3次照射,每次1min,總時間6min。(2)模擬IMRT組照射總時間15min。(3)模擬IGRT組照射總時間30min。各模擬照射組所受照射劑量同于常規(guī)照射組,放療物理師按照實(shí)際放療的模式進(jìn)行計(jì)劃設(shè)計(jì),分別對各個照射劑量點(diǎn)進(jìn)行照射,每個劑量點(diǎn)分7次照射,照射完成總時間分別為15min和30min。24小時后全部小鼠脫頸處死,切取腫瘤迅速用10%中性緩沖福爾馬林液固定,常規(guī)脫水、透明、包埋,石蠟切片,用TUNEL法測細(xì)胞凋亡指數(shù),并免疫組化法測凋亡相關(guān)基因蛋白bax和bcl-2。 結(jié)果1.各組凋亡指數(shù)差異明顯,有統(tǒng)計(jì)學(xué)意義(P0.01)。其中假照組的凋亡指數(shù)最低,常規(guī)照射組的凋亡指數(shù)最高。IMRT模擬組,IGRT模擬組與常規(guī)照射組比較,凋亡指數(shù)降低,差別均有統(tǒng)計(jì)學(xué)意義(P0.01);IMRT模擬組與IGRT模擬組之間差別無統(tǒng)計(jì)學(xué)意義(P=0.05);各照射組與假照組比較,凋亡指數(shù)均增高,差別有統(tǒng)計(jì)學(xué)意義(P0.01)。2.Bcl-2蛋白的半定量測定結(jié)果各組間均有差別。其中假照組的Bcl-2蛋白含量最高,常規(guī)照射組最低;常規(guī)照射組,IMRT模擬組,IGRT模擬組與假照組比較,Bcl-2蛋白含量均降低差別有統(tǒng)計(jì)學(xué)意義(P0.01); IMRT模擬組,IGRT模擬組與常規(guī)照射組之間比較,Bcl-2蛋白含量高,但差別無統(tǒng)計(jì)學(xué)意義(P=0.22)。3.各組Bax蛋白的半定量測定結(jié)果均有差別。其中假照組的Bax蛋白含量最低,其余各照射組與Bax蛋白含量均增高;IMRT模擬組,IGRT模擬組與常規(guī)照射組之間比較,Bax蛋白含量降低;IGRT模擬組較IMRT模擬組Bax蛋白含量低;差別有統(tǒng)計(jì)學(xué)意義(P0.01)。 結(jié)論高能X線照射時間延長會導(dǎo)致對小鼠鼻咽癌CNE-2Z細(xì)胞殺傷作用降低,具體表現(xiàn)在細(xì)胞凋亡指數(shù)下降,Bax升高程度與Bcl-2降低程度減小。提示在實(shí)際放射治療過程中應(yīng)該適當(dāng)增加總照射劑量來彌補(bǔ)放射生物效應(yīng)的損失。 第二部分照射時間延長對小鼠鼻咽癌CNE-2Z細(xì)胞MMP-9及E-cadherin表達(dá)的影響 目的模擬精確放療照射模式,觀察照射時間延長對小鼠鼻咽癌CNE-2Z細(xì)胞基質(zhì)金屬蛋白酶-9(MMP-9)及E-鈣黏附素(E-cadherin)表達(dá)的影響。 方法荷鼻咽癌CNE-2Z細(xì)胞雄性小鼠隨機(jī)分成4個組,每組10只:假照組,常規(guī)照射組,IMRT模擬組,IGRT模擬組。小鼠用10%水合氯醛(350mg/kg,腹腔注射)麻醉后固定于平板上,利用瓦里安23-EX加速器進(jìn)行一次性腫瘤靶區(qū)照射,6MV-X線,照射野給于1cm厚組織補(bǔ)償,總劑量18Gy,劑量率6Gy/min。(1)常規(guī)照射組分3次照射,每次1min,總時間6min。(2)模擬IMRT組照射總時間15mmin。(3)模擬IGRT組照射總時間30min。各模擬照射組所受照射劑量同于常規(guī)照射組,放療物理師按照實(shí)際放療的模式進(jìn)行計(jì)劃設(shè)計(jì),分別對各個照射劑量點(diǎn)進(jìn)行照射,每個劑量點(diǎn)分7次照射,照射完成總時間分別為15min和30min。24小時后全部小鼠脫頸處死,取出腫瘤迅速用10%中性緩沖福爾馬林液固定,常規(guī)脫水、透明、包埋,石蠟切片,HE染色,光學(xué)顯微鏡下觀察。用免疫組化測細(xì)胞轉(zhuǎn)移相關(guān)基因MMP-9及E-cadherin。 結(jié)果各照射組與假照組比較,MMP-9均降低,E-cadherin均增高,差別有統(tǒng)計(jì)學(xué)意義(P0.01); IMRT模擬組,IGRT模擬組MMP-9表達(dá)較常規(guī)照射組有所升高,其差別有統(tǒng)計(jì)學(xué)意義(P0.01);IMRT模擬組,IGRT模擬組E-cadherin表達(dá)較常規(guī)照射組有所下降,其差別有統(tǒng)計(jì)學(xué)意義(P0.01)。IMRT模擬組與IGRT模擬組MMP-9表達(dá)與E-cadherin表達(dá)無明顯差異。 結(jié)論高能X線在一定的范圍內(nèi),相同劑量下延長照射時間可導(dǎo)致MMP-9表達(dá)升高,E-cadherin表達(dá)降低,進(jìn)而導(dǎo)致放射治療抑制鼻咽癌CNE-2Z細(xì)胞的侵襲轉(zhuǎn)移的能力下降,影響其療效。
[Abstract]:Effect of irradiation time of first part on killing effect of CNE - 2Z cells in nasopharyngeal carcinoma

Objective To study the effect of irradiation time on the killing effect of CNE - 2Z cells and the expression of Bcl - 2 and Bax in nasopharyngeal carcinoma CNE - 2Z .

Methods Thirty male mice with nasopharyngeal carcinoma CNE - 2Z were randomly divided into four groups : sham group , routine irradiation group , IMRT simulation group and IGRT simulation group . All the mice were irradiated with 10 % chloral hydrate ( 350 mg / kg , intraperitoneal injection ) . The total dose was 18 Gy . The total time was 6 min . ( 2 ) The total time was 15 min and 30 min .

Results 1 . There was a significant difference in the apoptotic index of each group ( P0.01 ) . The apoptosis index of the sham group was the lowest , the apoptosis index of the conventional irradiation group was the highest , and the apoptosis index was decreased in the IMRT simulation group and the IGRT group compared with the conventional irradiation group ( P0.01 ) .
There was no significant difference between the IMRT simulation group and the IGRT simulation group ( P = 0.05 ) .
Compared with the sham group , the apoptosis index increased and the difference was statistically significant ( P0.01 ) . There was a difference in the semi - quantitative measurement of Bcl - 2 protein . The Bcl - 2 protein content in the sham group was the highest , and the routine irradiation group was the lowest .
There was no significant difference in Bcl - 2 protein content between IGRT group and normal irradiation group ( P = 0.22 ) , but there was no significant difference between the two groups ( P = 0.22 ) .
In the IMRT simulation group , the Bax protein content was decreased compared with the conventional irradiation group .
The expression of Bax was lower in IGRT group than in IMRT group .
The difference was statistically significant ( P0.01 ) .

Conclusion The prolonged irradiation time of high - energy X - ray can decrease the killing effect of CNE - 2Z cells in nasopharyngeal carcinoma . It is shown that the decrease of apoptosis index , the increase of Bax and the decrease of Bcl - 2 decrease . It is suggested that the total irradiation dose should be increased properly during the course of radiotherapy to compensate for the loss of radiation biological effect .

Effect of second part irradiation time on the expression of MMP - 9 and E - cadherin in nasopharyngeal carcinoma CNE - 2Z cells

Objective To study the effect of irradiation time on matrix metalloproteinase - 9 ( MMP - 9 ) and E - cadherin expression in nasopharyngeal carcinoma CNE - 2Z cells .

Methods Thirty male mice with nasopharyngeal carcinoma CNE - 2Z were randomly divided into four groups : sham group , routine irradiation group , IMRT simulation group and IGRT simulation group . All the mice were irradiated with 10 % chloral hydrate ( 350 mg / kg , intraperitoneal injection ) . The total dose was 18 Gy . The total time was 6 min . ( 2 ) The total time was 15 min and 30 min .

Results The expression of MMP - 9 and E - cadherin increased and the difference was statistically significant ( P0.01 ) , and the expression of MMP - 9 in IGRT group was higher than that in conventional irradiation group ( P0.01 ) .
In IMRT group , the expression of E - cadherin in IGRT group decreased significantly ( P0.01 ) . There was no significant difference between the expression of MMP - 9 and E - cadherin in the IMRT simulation group and IGRT simulation group .

Conclusion The increase of MMP - 9 expression and decrease of E - cadherin expression in nasopharyngeal carcinoma CNE - 2Z cells caused by high - energy X - ray irradiation could increase the expression of MMP - 9 and decrease the expression of E - cadherin in nasopharyngeal carcinoma CNE - 2Z cells .

【學(xué)位授予單位】:天津醫(yī)科大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2013
【分類號】:R739.63

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 黃偉,李寶生,于金明,尹勇,閆婧,劉同海,付政,余寧莎;主動呼吸控制方法在非小細(xì)胞肺癌精確放療中的應(yīng)用[J];腫瘤防治雜志;2005年08期

2 邢力剛,孫曉蓉,于金明,盧潔,劉娟,尹勇;PET-CT圖像融合精度對非小細(xì)胞肺癌放療計(jì)劃的影響[J];中華放射腫瘤學(xué)雜志;2005年04期

3 戴建榮;胡逸民;;圖像引導(dǎo)放療的實(shí)現(xiàn)方式[J];中華放射腫瘤學(xué)雜志;2006年02期



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