Medicine Feiliuping Cream On The Regulation Of Dendritic Cells

Tumor's formation is a slowly evolution process,in which the immunity is the most important anti-cancer mechanism.Antigen presenting cell(APC) is the key factor in immune response process in vivo.Dendritic cell(DC) is so far the strongest immune cell which has the ability to present antigen.The exertion of its function has close relationship with its maturity.DC's maturity completes with its immigration in different tissues.The interaction between Chemokine and Chemokine receptor is determinative factor to moves the DC migration,to adjust the DC circulation.The Chemokine receptor of DC is essential power for its migration from peripheral constitution to lymph node.We take DC as breakthrough point,try to reveal the sense of Strengthening Body Resistance and Consolidating Constitution theory through experimental study and clinical research.By experimental study,we compare the difference of DC maturity,DC migration and function bring by FLP and its decomposed recipes analysis(DRA) groups,to prove the function to adjust immunity by Benefiting vital energy medicine.Through clinical research,we discovered immune function with nonsmall-cell lung cancer(NSCLC) patients usually is in inhibitory state,and the change of DC subset is one of its performance,which is correlate with the TCM syndrome types.The clinical value is about prognosis.The FeiLiuPing Extract(FLP) can raise 1 year survival rate,lengthen live time.1.Influence of FLP & DRA on DC chemotactic functionWe use transwell to examine CI change of DC under action of IL-8 & RANTES and find that different TCM has different influence on DC chemotactic function. Under the action of IL-8,invigorating Qi herbs strengthens DC chemotactic function(CI=1.112),blood activating herbs(1.084),FLP(1.027),disintoxicating herbs is the lowest(0.874).Compare with YiQi group & HuoXue group,P＜0.05. Under the action of RANTES,FLP group get the highest CI(1.185),HuoXue group (1.075),YiQi group(1.048),JieDu group(0.917).Compare with FLP group,P＜0.01. The result is different kind of TCM has different influence on DC chemotactic function.With different chemotactic factor,it shows different effects,invigorating Qi herbs strengthens DC chemotactic function,while disintoxicating herbs inhibits DC chemotactic function..2.DC surface CCR7,CXCR4 change under the action of FLP&DRAThrough realtime-PCR method,the expression of chemotactic factor receptor CCR7,CXCR4 on DC surface was analyzed to clarify the molecular mechanism that different TCM changes chemotactic activity of DC.Results show that the expression of CCR7 in YiQi Group was the highest,while HuoXue Group,FLP Group lower, JieDu Group is the lowest.Comparing with YiQi Group,HuoXue Group & JieDu group,P＜0.05.The expression of CXCR4 in YiQi Group & FLP Group was highest, HuoXue Group is lower,JieDu Group is the lowest.Comparing with Blank Serum group and FLP group,YiQi Group,JieDu Group,P＜0.01.The results show that different TCM has differet inflence on chemotactic factor receptor of DC Surface. This is also one of the mechanism that with different chemotactic factor,different TCM has different action on DC chemotactic function.3.the dynamic imaging of T cells proliferation and regulation of Immunologic synapse(IS) with FLP and DRATo observe dynamic imaging about living cells including DC and T cells after culturing compounded Using two-photon laser scanning confocal microscope and flow cytometry technology.The immunological synapse(IS) and process of T cell proliferation were observed to discuss the regulating mechanism of anti-tumor immunity.The results showed that mutual migration and accumulation were observed 30 min later when mature DC and T cells were mixed in vitro,observed that the formation of IS 60 min later,after 120 min-1 Oh,with the IS formation,the T cells Obviously proliferation,mutual aggregation phenomenon intensified.And IS reduced after 20h,with gradually gathered more uniform distribution,in a certain time limit and the proliferation of T cells was certainly positive correlation to IS. FLP and invigorating Qi herbs may promote the formation of IS,extend the time of combination.FLP is superior to its DRA in regulating IS formation and proliferation effect of T cells,P＜0.05 or 0.01.The effects were more obvious with time extension. Compared to other groups,JieDu group inhibited it to a extent,P＜0.05 or 0.01.All results show the formation of IS play an important role in the the proliferation of T cells stimulated by DC.FLP can enhance DC-antigen-presenting function,and promote IS formation,so as to stimulate T cell proliferation.4.FLP & DRA's inflence on DC stimulating LPAK anti-tumor activityComparing FLP & DRA's different influence on DC sitmlating LPAK anti-tumor acitivity and dicussing the different action of DC-LARK under different TCM,provides an initial experimental basis on clinical medication.Research found that the killing activity is significantly higher than comparision group when LPAK: Tumor(L:T) eaquals 10:1 or 5:1,all P＜0.05.When L:T eaquals 10:1,FLP group, compare YiQi Group,HuoXue Group and JieDu group with comparision group,all P＜0.05.When L:T eaquals 5:1,compare all TCM group with comparision group,all P＜0.05.FLP,invigorating Qi herbs,blood activating herbs has higher effects than disintoxicating herbs.Comparing within groups,i.e.comparing L:T(10:1) with L:T(5:1),JieDu Group,blank DC group,PL group,P＜0.05.The balanced group, P＞0.05.FLP group,YiQi Group & HuoXue Group has similar effects on stimulating LPAK's killing acitivity,while L:T eaquals 10:1 or 5:1.This shows that FLP,blood activating herbs & invigorating Qi herbs can strengthen the action of DC stimulating DC-LPAK of killing tumor cells to different extent,however,disintoxicating herbs has little inhibition action.5.The CTL and proliferative capacity of T cell in spleen of Lewis lung cancer with FLP and DRATo compare CTL and proliferative capacity of T cell in spleen of Lewis lung cancer with FLP and DRA.The results showed that T-lymphocyte proliferation of all bearing-tumor groups were lower than the normal group,P＜0.01.FLP group was lower than normal group,but higer than others,P＜0.05.The rate of CTL to CD8~+T in FLP group and CTX group were both rising,compared to the model group, P＞0.05.we concluded that FLP could enhanced proliferative capacity of T cell and increased the rate of CTL,which were one of its immune mechanism to resist cancer.6 Sense to determinate DC subset in Peripheral blood of NSCLC patients 99 NSCLC patients were chosen to compare with 23 healthy volunteer.To observe the changes of NSCLC patients's Peripheral blood DC subsets and discuss its relationship with clinic features,ROC curve was adopted to compare its specificity and sensitivity.Results show that the patients's DC1 percentage is significantly lower than comparision group(P=0.009);DC2 has no obvious change(P=0.655),DC1/DC2(P=0.177);DC1,DC1/DC2 has significant difference(P=0.032,0.001),DC1 has obvious difference between different KPS(P=0.023).To analyse ROC curve of DC1,DC1/DC2 ratio in Peripheral blood of Lung cancer patients,the area under the curve is 0.671,0.702(P=0.011,0.003). DC1/DC2 has relationship with survival time.Patients with more than 1 year survival time compare with less than one year patients,P=0.028.Both Logistic and Cox analysis show that DC1/DC2 has relationship with Lung cancer patients's survival time,which is Lung Cancer patients's independent prognostic factor.(P=0.034,0.024).This shows that monitoring Peripheral blood DC subsets of NSCLC patient is conducive to a comprehensive understanding of its immunization status and predicting the prognosis.7.Relevant research on Peripheral blood DC subsets of NSCLC patients & with the TCM syndrome types99 NSCLC patients were chosen to study the relevance of DC subsets and the TCM syndrome types.Research found that the TCM syndrome types of lung cancer has no obvious relevance to patient's sex,age,pathology as well as KPS & CEA. DC1 & DC2 has no great difference between each type.Decending sequence of DC1 is:deficiency of vital energy and phlegmatic hygrosis,yin asthenia and pyretic toxicity,energy-stagnation and blood stasis,deficiency of both vital energy and yin. and DC2 was:deficiency of vital energy and phlegmatic hygrosis,deficiency of both vital energy and yin,yin asthenia and pyretic toxicity,energy-stagnation and blood stasis.DC1/DC2 ratio value have obvious difference in each type,P=0.012, deficiency of vital energy and phlegmatic hygrosis is the highest,deficiency of both vital energy and yin is the lowest.The Results of survival analysis on Lung cancer patiens of different types shows that only yin asthenia and pyretic toxicity has a lower survival rate.The other types has no obvious changes,deficiency of vital energy and phlegmatic hygrosis is a little higher.With Log-Rank analysis,x~2=6.051, P=0.109.This shows that DC1/DC2 has some relevance to TCM syndrome types of Lung cancer.8.Clinic research on NSCLC patient's immune status & prognosis with FLP60 NSCLC patients was divided into two groups randomly,30 in treatment group and 30 comparision group.Patients in threatment group were treated with FLP plus chemotherapy,while the comparision group only with chemotherapy.In the mealtime,to observe the changes of recent curative effects,immue function and survival period.Results show that curative effects is:Treatment group has CR 0 case, PR 9 cases,SD 14 cases,PD 6cases,the effective percentage is 33.33%,while the comparision group has CR Ocases,SD 13cases,PD 10cases,the effective percentage is 26.67%,P＞0.05.Patients of treatment group has higher DC1,DC1/DC2,NK cells comparing with the comparision group(P＜0.05,0.01,0.05seperately).Survival analysis shows that one year survival rate of treatment group is 43%,while the comparision group is 28%.Comparision of total survival period of the two groups (x~2=1.764,P=0.184).This show that FLP plus themotherapy can obviouly promote the proliferation of NK cells,adjust the change of DC subsets,improve immune function,hence increase the one year survival rate of lung cancer patients,improve life quality and prolong survival.9.Comparative study of relations between curative effect & prognosis of patients with lung cancer and T lymphocyte subsets & DC subsetsObserving the ralationship between lung cancer patient's post-treatment T lymphocyte & DC subsets and survival period,assess the value of clinic curative effets.Results show that patients with rising CD4+/CD8+ have 38%one-year survial rate,on the contrary,has a survival rate of 36%,the difference have no statistic significance(x~2=0.100,P=0.752).Patients with rising DC1/DC2 have a 50% one-year survival rate,on the contrary,24%(x~2=6.769,P=0.009).With DC1/DC1 plus survival period as variables,we do bivariate relevance analysis,the Spearman's correlation coefficient is 0.302,P=0.019,which means a significant relevance.This shows that changing of DC1/DC2 has much more clinic significance to the estimation of lung cancer prognosis.Those patients who has a rising rate after treatment will survive longer.ConclusionEmperiment study1.FLP,invigorating Qi herbs and blood activating herbs can promote DC migration,disintoxicating herbs inhibit DC migration,the mechanism is that different herbs has different influence on the expression of chemotactic factor receptor on DC surface.2.FLP & invigorating Qi herbs can both promote the formation of IS(the mixed culture of DC & T cell),prolong its combination period,thus to promote the proliferation of T cells.Disintoxicating herbs shows a certain inhibition trend.3.DC could obviously increase LPAK cell's killing activity to tumor cells.FLP, blood activating herbs and invigorating Qi herbs has synergism to some extent, whereas disintoxicating herbs has the contrary effects.4.FLP can enhanced proliferative capacity of T cell and increased the rate of CTL,which were one of its immune mechanism to resist cancer.Clinical study1.FLP can raise lung cancer patient's one-year survival rate,improve life quality,prolong survival period and improve immune function,which DC1 an d DC1/DC2 ratio were raised.2.DC1/DC2 is related with survival time,and is the independent prognos tic factor for the survival of patients with lung cancer.It is helpful for prognos is to monitor DC subsets of NSCLC patients.3.DC1/DC2 is in relevance with TCM syndrome types.We should invest igate further.