Research About The Mechanism Of Adenoid Cystic Carcinoma Of Lacrimal Gland On Onset And Metastasis And Experimental Study Of The Treatment With ¹²⁵I Seeds Interstitial Brachytherapy

Objective1 To investigate the expression and correlation of MVD,VEGF,PCNA,MMP-2 andMMP-9 in human adenoid cystic carcinoma of lacrimal gland as well as their relationwith biological behaviour of human adenoid cystic carcinoma.2 To provide experimental basis for clinical application of ¹²⁵â… seeds interstitialbrachytherapy by investigating the influence of iodine -125 seeds on the transplantedACC of BALB/C nude mice,the surrouding nomal tissue,the blood cells,the influenceof proliferative,angiogenetic and metastatic factors and the relationship between theradioactivity of ¹²⁵â… and the effect of treatment.3 To provide reference for clinical program of ¹²⁵â… seeds interstitial brachytherapy byinvestigating the relationship between radioactivity and max effective radius of 125â… seeds by detect the position of apoptosis and necrosis with transmission electronmicroscope.Methods1 The expression of CD105,VEGF,PCNA,MMP-2 and MMP-9 was evaluated in the60 operative samples of adenoid cystic carcinoma of lacrimal gland as well as 10samples of normal lacrimal gland around tumor by immunohistochemistry.The MVDwas defined by expression of CD 105.2 ACC-2 cells were transplanted subcutaneously in the back of BALB/C nude mice,thirty transplanted ACC models were produced,twenty-five fitable models wereselected to take the animal experimental research and separately divided into fourdifferent therapeutic radioactivity group and a control group,each group included 5nude mices.Oneâ… ¹²⁵ seed (surface radioactivity 0.4mci,0.6mci,0.8mci,1.0mci) wasimplanted into each tumor of mice in treatment groups with Dose-volumeHistogram(DVH) being measured by treatment planning system(TPS),while each mice incontrol group was implanted into one iodine -125 seed with 0mci surface radioactivity.Tumors' dimensions of tumors were measured per 2 days and tumor volumeinhibition rates were calculated.The blood cells of nude mice were also observedafter treatment.Nude mice were killed after 14 days,transmission electron microscope and routine pathological examination proceeded to detect the apoptosis and necrosisand the max effective radius.The expression of PCNA,VEGF,MMP-2,MMP-9 andCD 105 were examined with immunohistochemical methods in five groups.Results1 The number of MVD and the positive rate of VEGF,MMP-2,MMP-9 and PCNAin the samples of human adenoid cystic carcinoma of lacrimal gland were asfollowing:(17.71±5.63),53.33%(32/60),45.00%(27/60),55.00%(33/60),46.67%(28/60);while,the number of MVD in normal lacrimal gland is(0.70±0.95),and there is no positive expression for VEGF,PCNA,MMP-2 and MMP-9.Therewere significant difference between two groups (P＜0.05);2 The number of MVD and the positive rate of VEGF,MMP-2,MMP-9 and PCNA inhuman adenoid cystic carcinoma of lacrimal gland weres correlated with pathologicaltype and recurrence (P＜0.05).But not with age and sex(P＞0.05);3 The number of MVD in ACC of lacrimal gland patients was correlated with theexpession of VEGF,MMP-2,MMP-9 and PCNA respectively (r_s=0.834,p＜0.05;r_s=0.636,p＜0.05;r_s=0.524,p＜0.05;r_s=0.742,p＜0.05);4 The expression of VEGF in ACC of lacrimal gland patients was correlated with theexpession of MMP-2 and MMP-9 respectively (r_s=0.646,p＜0.05;r_s=0.524,p＜0.05);The expression of PCNA in ACC of lacrimal gland patients was correlated with theexpession of VEGF,MMP-2 and MMP-9 respectively (r_s=0.712,p＜0.05;r_s=0.546,p＜0.05;rs=0.612,p＜0.05);5 There was no significant deference between treatments and control group in redblood cell count,hemoglobin,white blood cell count and platelet count (P＞0.05);6 The dimension of tumors in every groups were measured after 14 days treatmentand the dimension of each treatment group(3713.19±243.23)mm³ was large comparedwith control group.The tumor inhibition rate of treatment groups were as following:G₁(20.11±3.09)%,G₂(36.18±2.54)%,G₃(40.83±4.17)%,G₄(66.63±5.34)%.Thecorrelative analysis results of each treatment groups showed that the radioactivity of¹²⁵â… has positive correlation with the tumor inhibition rate.(r=0.965,P=0.035);7 Result of transmission electron microscope showed that the the max effective radius ofeach treatment groups were G₁5.2mm,G₂ 6.4mm,G₃ 7.4mm,G₄ 8.2mm,The correlative analysis results showed that the radioactivity of ¹²⁵â… has positive correlation with thethe max effective radius (r=0.9960,P=0.0040).8 The number of MVD and the level of PCNA,VEGF,MMP-2,MMP-9 in treatmentgroups were all decreased compare with the control group (P＜0.05);9 The correlative analysis results of each treatment groups showed that theradioactivity of ¹²⁵â… has negative correlation with the level ofVEGF,MMP-2,MMP-9,PCNA and the number of MVD (r=-0.9973,P=0.0026;r=-0.9961,P=0.0039;r=-0.9985,P=0.0014;r=-0.9777,P=0.0223;r=-0.9597,P=0.0403);the level of VEGFpositive correlation with the level of MMP-2 and MMP-9(r=0.9948,P=0.0051;r=0.9998,P=0.0002).Conlusion1 The number of MVD and the expression of VEGF,MMP-2,MMP-9 and PCNA inhuman adenoid cystic carcinoma of lacrimal gland were high level in human adenoidcystic carcinoma of lacrimal gland.2 The number of MVD and the expression of VEGF,MMP-2,MMP-9 and PCNA inhuman adenoid cystic carcinoma of lacrimal gland were significantly correlated withpathological type and recurrence;while,there is no correlated with age and sex.3 The expression of VEGF,PCNA,MMP-2 and MMP-9 were significantly correlatedwith angiogenesis of human ACC of lacrimal gland.Detecting the number of MVDand the expression of VEGF,PCNA,MMP-2 and MMP-9 may be become biologicalindex for malignancy and recurrence of adenoid cystic carcinoma of lacrimal gland.4 ¹²⁵â… seed implantation brachytherapy may inhibit the growth of the transplantedACC of BALB/C nude mice by inhibiting proliferation of tumor cells,anddown-regulating angiogenesis and metastasis.¹²⁵â… interstitial brachytherapy is a safe,feasible and effective method to treat ACC and it has no significant side effect.5 The max effective radius of each treatment groups were G₁ (5.2±0.5)mm,G₂ (6.4±0.7) mm,G₃ (7.4±0.4) mm,G₄ (8.2±0.5) mm,those data have referentialmeaning for clinical program of ¹²⁵â… interstitial brachytherapy.6 ¹²⁵â… seed implantation brachytherapy may inhibit neovascularization by inhibitingthe expression of VEGF,MMP-2 and MMP-9 in ACC cell to inhibit the growth,invasion and metastasis.