| Objective:To observe the clinical efficacy of Jian Pi HuaTan prescription combined with systematic chemotherapy in the treatment of liver metastasis of colorectal cancer,and to explore the anti-metastasis mechanism of TCM compound.Methods:Clinical study:47 patients with CRLM who were admitted to the oncology ward and outpatient department of the second affiliated hospital of nanjing university of traditional Chinese medicine and met the TCM syndrome pattern of spleen deficiency and phlegm and blood stasis.There were 25 cases in the treatment group and 22 cases in the control group.8 weeks after the treatment,CT scan of the whole abdomen and chest was reexamined and enhanced,and the efficacy of solid tumor was evaluated.Changes of AFP,CEA,Ca199,Ca724 and Ca125 before treatment;l year follow-up:the total survival time of enrolled patients was calculated;1-year overall survival rate;No time of disease progression;The scores52.Kang,H.L,Russell,et al.Nivolumb as salvage treatment after second or later-line chemotherapy for of physical condition of the patients were observed at 8 weeks after treatment.The score of TCM symptoms;Blood indexes related to toxic and side effects after treatment;Experimental research:(1)to study the effect of Jian Pi HuaTan prescription on the activation level of CAFs in nude mice with metastatic liver tumors of colon cancer.(2)to study the effects of Jian Pi HuaTan prescription on the activation of TAMs,the expression of MMP-2 and the formation of VM in liver metastases of colon cancer in nude mice.(3)to study the effect of Jian Pi HuaTan prescription on the expression of Akt,HIF-1 levels and VEGF proteins in human colon cancer liver transplantation tumors of nude mice.Results:Clinical research section1.Efficacy evaluation of solid tumor:after treatment,the effective rate of the two groups was basically the same,and the disease control rate of the treatment group was higher than that of the control group,with no statistical difference.The results showed that after 8 weeks of taking Chinese herbal compound,jianpi huatan prescription failed to show obvious clinical advantages in improving the efficacy of liver metastases.2.Efficacy evaluation of TCM symptoms:after treatment,the efficacy score of patients withTCM symptoms was analyzed,and the effective rate of the treatment group was higher than that of the control group(P=0.034<0.05).The difference was statistically significant,indicating that tongtai mixture could improve the TCM symptoms of patients.3.Evaluation of serum tumor markers:before treatment,there was no significant difference in CEA between the treatment group and the control group(Z=-0.548,P=0.314>,0.05),CA724,CA125,and CA199.After treatment,there were significant differences in CEA between the treatment group and the control group(Z=-0.468,P=0.036<0.05),CA724,CA125 and CA199.Both CEA and CA199 in the treatment group decreased after treatment compared with before treatment,showing statistical significance(P=0.019<0.05),and CA199 showed statistical significance(P=0.025<0.05).Both CEA and CA199 in the control group decreased after treatment compared with before treatment,and the difference of CEA before and after treatment was statistically significant(P=0.037<0.05),and that of CA199 was statistically significant(P=0.036<0.05).This indicated that the TCM compound combined system treatment group had advantages in improving the CEA level of CRLM patients,while it did not show obvious advantages in the aspects of CA199,CA125 and CA724.4.Evaluation of toxic and side effects:the effect of leukocyte,hemoglobin and platelet in the treatment group was lower than that in the control group,but there was no significant statistical difference(P>0.05),and there was no significant difference between the two groups in the liver and kidney toxic and side effects.5.Comparison of KPS scores:after 8 weeks of treatment,the improvement of KPS in the treatment group was more obvious than that in the control group.As the data did not conform to the normal distribution,the results showed that Z=-2.236,P=0.042<0.05,and the difference was statistically significant.In the treatment group,there were 5 cases of improvement,17 cases of stabilization,and 2 cases of deterioration,with the stabilization rate of 91.66%.In the control group,there were 0 cases of improvement,22 cases of stabilization,and 1 case of deterioration,with the stabilization rate of 95.65%.6.Comparison of PFS,OS and 1-year survival rate:there was no statistical difference in PFS and OS between the treatment group and the control group within 1 year of follow-up after treatment,but the PFS and OS were higher in the treatment group than in the control group(7.67vs6.09,10.73vs 10.02).The 1-year survival rate of the treatment group was significantly higher than that of the control group(54.16%vs30.43%,P=0.0024<0.05).Experimental research section:Western Blotting was used to detect the effect of spleen-strengthening and phlegm-removing formula on the expression of hif-1 levels,VEGF and Akt proteins in the liver transplantation tumor of colon cancer in nude mice.The experimental results showed that hif-la protein was highly expressed in the model group,and its expression decreased significantly with the increase of the concentration of traditional Chinese medicine.VEGF protein was highly expressed in the model group,and its expression decreased significantly with the increase of TCM concentration.VEGF protein was highly expressed in the model group,and its expression decreased significantly with the increase of TCM concentration.Akt protein was highly expressed in the model group and the traditional Chinese medicine group,and there was no significant difference in its expression with the increase of the concentration of traditional Chinese medicine.Conclusion:The application of spleen-strengthening and phlegm-removing prescription combined with systematic chemotherapy in liver metastasis of colorectal cancer can improve the TCM symptoms of patients,reduce the bone marrow suppression and gastrointestinal reactions caused by chemotherapy,and improve the quality of life.In vitro experimental studies have proved that strengthening spleen and eliminating phlegm may inhibit the development of liver metastases by inhibiting the activation level of CAFs in the microenvironment of liver metastases and inhibiting the activation level of TAMs.Improve the oxygen concentration of liver metastases,inhibit the expression of hif-1,and thus inhibit tumor angiogenesis.The development of liver metastases was inhibited by decreasing the expression of MMP-2 and inhibiting the formation of VM. |
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