Observation Of Infiltration And Activation Of Dendritic Cell In Primary Foci Of Prostate Cancer Using "Fuzhengyiliufa" Integrative Treatments

BackgroundProstate cancer(PCa) is one of the malignant tumors of man's reprodu ctive system.In US,the incidence of prostate cancer is listed in the fi rst place of the man's malignant tumors'.In China,its incidence has be en up rising to the 3^rd place of all the urinary tumors'.Most of the indi viduals were diagnosed to be prostate cancer in their later period of can cer progression.Moreover,nearly all of the patients who had received th e incretion therapy would eventually turn to be the hormone refractory ca ses.This makes it tough for Modern Medicine to cure.Urinary Surgical De partment of Guangdong Provincial Hospital of Chinese Medicine had for lon g concentrated on the study of prostate cancer,and had initially explore d its etiology,pathogenesis and syndrome differentiation.The regular pa tterns of Prostate cancer are as follows:Phase D₀:spleen Qi deficiency, kidney Qi deficiency.Phase D₁:blood stasis,lower energizer damp-heat, kidney Qi deficiency.Phase D₂:spleen Qi deficiency,blood stasis,lowe r energizer damp-heat,kidney Qi deficiency,Yin deficiency and phlegm he at,deficiency heat.Phase D₃:Qi and blood deficiency.The according int egrative treatment protocols according to TCM concept "Fuzhengyiliufa" w hich has enhancive effect of quality of life and postponement of tumor pr ogress and metestasis had later been developed,demonstrated good prospec t in clinical used.Prospective study of 142 available cases of inpatient or outpatient in Guangdong hospital of TCM from Sep.2004 to Mar.2007 h ad been conducted.The treat period was 9 months.Collected information o f Karnofsky table,weight,QLQ-C30 table,I—PSS table,ache ctassificatio n table of WHO,table for research in symptom category of prostate cancer in D period,PSA,blood testosterone,ECT of systemic bones,analysis of blood corpuscle.The remedy group is obviously better than the control group in increasing weight,improving the scale of Karnofsky table,alle viating symptoms such as tiredness,pain,insomnia,appetite losing,p ressing breach,constipation,diarrhea,improving the emotion function a nd health condition in whole;improving the symptom of lower urethra;red ucing the incidence rate of the symptom such as tiredness and fatigue,in somnia,desudation,poor appetite,difficult in urethra,pain in waist an d knee,etc.,reducing the amount of PSA and bone metastasis(P＜0.05),enh ancing the amount of blood corpuscle such as WBC,HGB,PLT in circulation. In recent clinical practice,cellular immunity function decline was seen in all prostate cancer patients.While majority of patients' cellular im munity function were seen to be enhanced after the application of "Fuzhen gyiliufa" integrative treatment.This is precisely the same goal that all immunotherapies take hope to achieve.In human immune system,specific c ellular immunity plays a key role in fighting against tumor.While dendri tic cell(DC) is deemed to be the most powerful antigen precenting cells, which is the initiator of specific immunity.However,dendritic cell-bas ed immunotherapies only manifest the transient curative effect in partial PCa patients.Since "Fuzhengyiliufa" has been observed to have effect i n immunity function,its influence in dendritic cell should be further ex plored.PurposesTo observe the infiltration and activation of dendritic cell in prima ry foci of prostate cancer using "Fuzhengyiliufa" integrative treatments.MethodsPerspective research,control trail,57 prostate cancer in-patients w ere intaken in the study.The first group 18 patients,who had obtained p athological specimens before and after treatments respectively,were divi ded into two subgroups,therapeutic group 10 patients,and control group 8 patients.The therapeutic group received "Fuzhengyiliufa" integrative t reatment("Fuzhengyiliufa" TCM treatments combined with routine incretion therapy),the control group receieved routine incretion therapy,and the therapeutic period ranged between 7 days to 105 days.The second group 3 9 patients,who had only obtained 1 pathological specimen in each,were d ivided into two subgroups according to whether patients received "Fuzheng yiliufa" TCM treatment or not before their biopsy:therapeutic group 19 pa tients;blank control group 20 patients.The therapeutic group received "Fuzhengyiliufa" TCM treatments,the therapeutic period ranged between 7 to 25 days,8.7 days in average;control group didin't received any trea tment,then marked the CD1a positive dendritic cell and the CD83 positive dendritic cell which infiltrated in these pathological sections with the immunohistochemistry technique of "Envision" two step staining,and rec orded the quantities of these dendritc cells with microscope.The negativ e ones would be recorded as "0" in quatity.As for statistics analysis, dependent t-test would be used to compare means of dependent groups if th e variance meets Gaussion distribution,if not,non-parametric test(Mann -Whitney Test) would be applied,p＜0.05 has the significance for the diff erence.Pair groups t-test would be used to compare means of pair groups if the variance meets Gaussion distribution,if not,non-parametric test (Wilcoxon Test) would be applied,p＜0.05 has the significance for the dif ference.Statistic analysis software SPSS13.0 would be applied.Results1.The first group 18 patients who had obtained twice pathologic samp les in each,therapeutic subgroup 10 patients,with 1 before treatment sa mple CDla negative and 1 before treatment sample CD83 negative;Control s ubgroup 8 patients,with 1 after treatment sample CD1a negative and 1 aft er treatment sample CD83 negative.The quantity of CD1a positive DC after treatment in both groups elevated compared to the quantity of CD1a befor e treatments,the differences had statistical significance.The quantity of CD83 positive DC after treatment in therapeutic group elevated compare d to the quantity of CD83 positive DC before treatment,the differences h ad statistical significance,P≤0.05.The quantity of CD83 positive DC af ter treatment in control group elevated compared to the quantity of CD83 positive DC before treatment,the differences had no statistical signific ance,P＞0.05.The quantity difference of CD1a positive DC of therapeutic group were more than the ones of control group,the differences had no st atistical significance,P＞0.05.The quantity differences of CD83 positive DC of therapeutic group were more than the ones of control group,the di fferences had statistical significance,P＜0.05.2.The second group 39 patients,who had obtained one pathologic samp le,therapeutic group 19 patients,with 1 sample CD1a negative;blank con trol group 20 patients,with 3 sample CD1a negative and 2 sample CD83 neg ative.The quantity of CD1a positive DC in therapeutic group surpass blan k control group,the difference had statistical significance,P＜0.05.The quantity of CD83 positive DC in therapeutic group surpass blank control group,the difference had statistical significance,P＜0.05.3.Single use of "Fuzhengyiliufa" Chinese Medicine group elevated CD8 3 in quantity compared to blank control group,the differernce had statis tical significance,P＜0.05.4.In descriptive study of comparision of various "Fuzhengyiliufa" tr eatments,it could be seen that the CD1a,CD83 elevating effect of conbine d used of herbal decortions and herbal injections were better than single use of herbal decortion,the differences had statistical significance,P＜0.05.5.It could be observed with microscope in blank control group PCa pa tients' pathological section that the infiltrated dendritic cell declined in quatity and disfunction in activating.Marked by CD1a and CD83,dendr itic cells were stained in their cytoplasmid and nuclear,appeared immatu re in shape that less like dendritic form.Their staining is lighter than the ones in benign hyperplasia tissues,with prominent decline in CD83. Dendritic cell infiltration is more concentrating in mesenchrymal tissues beside tumor tissue with infiltrated lymphocyte arround.In therapeutic group PCa patients' pathological sections,infiltrated dendritic cell are much more in quantity.Dendritic cell infiltration is more concentrating, not only in mesenchrymal tissues but also in between the tumor cells.Th ey appeared more mature in dendritic form,staining darker.Moreover,the dendritic cells,marked by CD83,are more mature in shape with more conc entrating infiltrated lymphocytes around. Conclusions1.Infiltrated dendritic cells in prostate cancer primary foci were l ess than the ones in benign hyperplasia tissues in quantity.Their activa tion was inhibited.The application of "Fuzhengyiliufafa" integrative tr eatment protocol could increase the quantity of dendritic cell in prostat e cancer primary foci and greatly enhance their activating ability in cer tain therapeutic period.2.It could be seen that the DC quantity elevating effect and the DC activation reinforcement effect of integrative therapy of Chinese Medicin e and incretion therapy and the combination of herbal decortions and inje ctions had advantage over other single used treatments.3.It could be observed that with the elevated quantity and activatin g ability of dendritic cell,local lymphocytes infiltration became more c oncentrating.The probable mechanism was that activating dendritic cells precent tumor antigens to activate T lymphocytes.That leads to prolifera tion and expansion of T lymphocyte.In that way specific immunity was ini tiated.