| The incidence rate of colorectal cancer has gradually increased in China for the past few years, and this accounts for a big portion of the mortality rate. Radical surgery is the most important and most effective treatment for colorectal cancer, and it is the only means to achieve a cure. Despite the use of adjuvant chemotherapy,20～50% of stage II and III colorectal cancer patients will relapse after radical chemotherapy and develop into incurable metastatic disease. Traditional Chinese Medicine (TCM) plays an important role in postoperative long-term treatment of colorectal cancer. This research focuses on the mechanism of strengthening spleen and nourishing kidney methods on treating patients with stage II and III colorectal cancer against metastatic and recurrent.This paper consists three parts:The first part is literature review. The author of this paper looked into evidence of the TCM understanding of colorectal cancer, as well as the recent progress in the popular topic of immune therapy researches-double negative T-cells. The second part are experimental studies of two TCM formulas, Liuweidihuang and Sijunzi decoctions, which might play an important role in mechanism of immune regulation process prohibiting postoperative recurrences. The third part are clinical researches. It compared the differences in TCM syndromes and related prognoses which lead to the mechanism of strengthen spleen nourish kidney treatment and its relationship with immune regulation in the postoperative anti-recurrences. The following highlights briefly describes experimental and clinical studies:Experimental Study:Objective:To observe TCM formula Liuweidihuang and Sijunzi s impact on CT26 colon carcinoma cells and tumor-bearing mice’s peripheral blood lymphocytes and regulatory cytokines.Methods:CT26 colon Balb/c mice xenograft models were constructed, and were randomized into four groups. They were given Sijunzi decoction, Liuweidihuang decoction and normal saline respectively (another group was normal blank mice without intervention) for 14 days. Tumor volume, mass, visceral index, survival time and lymphocyte and cytokine were analyzed afterwards.Results:1) The tumor inhibition rate of Sijunzi group was 17.82%, and the tumor inhibition rate of Liuweidihuang group was 3.95%.2) The tumor volume growth curve shows two TCM group grew more slowly compared to the control group.3) Tumor-bearing mice compared to normal mouse has a lower thymus index and a higher spleen index; both index were increased after oral intake of TCM medicine.4) Compared with normal mice, tumor-bearing mice IFN-y, IL-5, IL-13 expression was significantly reduced and TNF-a, IL-6, KC expression is higher. IL-2, IFN-y levels of Sijunzi group and Liuweidihuang group were significantly elevated while Liuweidihuang group showed significantly decreased in IL-1 β.5) Compared to normal mice, tumor-bearing mice has elevated white blood cells, neutrophils and lower hemoglobin. Sijunzi group showed a trend of reduction in the high white blood cell while Liuweidihuang group significantly improved anemia status and lymphocytes tended to increase.6) Compared to normal mice, tumor-bearing mice’s total T cells. CD8+T cells. CD4-CD8+T cells. CD4+CD25+T cells and CD4+CD25-Foxp3+T cells was significantly increased. CD8+T cells. CD4-CD8+T cells of Sijunzi group decreased. CD4+CD8-T cells showed the trend to increase. Liuweidihuang group has an increased total T cells and total B cells:7) Compared with normal mice, tumor-bearing mice CD4+/CD8+ ratio. DNT cell levels were significantly reduced. CD4+/CD8- ratio was significantly increased in Sijunzi and Liuweidihuang groups, and Sijunzi group relatively more obvious. Liuweidihuang group was more significant in the growth of DNT cells.Conclusion:Sijunzi and Liuweidihuang formulas may inhibit the growth of colon cancer CT-26 cells in mice, and may prolong the survival. It may be related to the regulation of cytokines, Th1/Th2 cells balance and DNT cells. Sijunzi decoction may play a role in immune regulation by regulating cytokines. while Liuweidihuang decoction by regulating immune cells.Clinical Study I:Association between Traditional Chinese Medicine Diagnoses and Prognoses in Postoperative Patients with Stage Ⅱ & Ⅲ Colorectal CancerObjective:To determine the association between Traditional Chinese Medicine (TCM) syndromes and prognoses in postoperative patients with Stage Ⅱ & Ⅲ Colorectal Cancer.Methods:We retrospectively analyzed outpatients of Stage Ⅱ and Ⅲ Colorectal Cancer after Radical Surgery from TCM oncology clinic in Xiyuan Hospital between Jan 1, 2000 and April 1,2015. Patients with metastasis recurrence within 5 years after surgery (excluding the group whose recurrences appeared within six months), were the case group. And patients with more than five years whose recurrence did not appear, served as the control group. Case and control group ratio was 1:4, paired according to nested case-control study. They were compared by age, gender, tumor location, TNM stage, TCM syndromes, adjuvant therapy and cumulative TCM treatment time.Results:Comparison between the two groups by age, gender, tumor location, stage and adjuvant therapy showed no significant difference (P>0.05). Higher proportion of cases had syndrome of disharmony between liver and spleen (P<0.05) than that in the control. On the other hand, the control group had higher proportion of the syndrome of deficiency of spleen and kidney than that in the case group (P<0.05). Cumulative TCM treatment time of more than 6 months or 1 year is deemed statistically significant. To further clarify on this problem, a logistic regression model was established. The results showed cumulative TCM treatment time was a protective factor on prognosis(OR<1). and syndrome of yin deficiency of liver and kidney (OR> 1) increased risk of recurrence compared with syndrome of deficiency of spleen and kidney.Conclusion:We found that specific TCM syndromes may be associated with prognosis in patients with stage Ⅱ and Ⅲ colorectal cancer. The prognoses of syndrome of yin deficiency of liver and kidney tend to be less positive. TCM treatment may improve the prognosis. and there may be differences in how colorectal cancer patients benefit from different TCM treatments.Clinical Study Ⅱ:The impact on immune function of patients with stage Hand Ⅲ postoperative colorectal cancer by using strengthening spleen and nourishing kidney treatmentObjective:To explore the different modern medicine characteristics of spleen deficiency, kidney deficiency and both spleen and kidney deficiency syndromes in stage Ⅱ,Ⅲ patients with colorectal cancer, on the basis of Clinical Study I. To explore the mechanism of how strengthen spleen and nourish kidney method adjust immune regulation.Methods:Utilizing the cohort study method, the author analyzed 65 patients cases recruited at Xiyuan Hospital Center since August 19,2014 February 20,2016. Data were collected and analyzed about their TCM syndromes, general information, lifestyle, clinical data, treatment, pathological data, gene status, recurrence and metastasis, and immune function before and after treatment.Results:1) No statistical difference were observed in general information, physical status, lifestyle, medical history, history of cancer, tumor location, TNM stage, pathological data, gene status and treatment in the three syndromes:spleen deficiency syndrome, kidney deficiency syndrome, both spleen and kidney deficiency syndrome(P >0.05).2) NK cells, Th17 cells and Th17/Treg levels were lower in kidney deficiency group than the other two groups. Correlation analysis showed that kidney deficiency syndrome was related to the normal level of Treg cells and low level of NK and Th17 cells. Spleen deficiency Syndrome was related to the normal level of Th17 cells and low level of NK and Treg cells. Syndrome of both spleen and kidney deficiency was related to the normal level of Th17, NK and Treg cells.3) Nourishing kidney treatment can improve the level of Th17 cells, and Strengthen spleen method can reduce Th17 and Th17/Treg ratio (P<0.05).4) TCM treatment can reduce the level of Th2 cells, particularly in the strengthening spleen and nourishing kidney method.5) TCM treatment can increase the level of B lymphocytes, in which strengthening spleen method is the most significant.6) The 1-year recurrence rate of metastasis was 0%,0% and 11.11% for spleen deficiency, kidney deficiency and both spleen and kidney deficiency group respectively (P>0.05).7) TCM-related adverse reaction rate was 7.69%(5/65).Conclusion:Syndromes of spleen deficiency, kidney deficiency and both spleen and kidney deficiency may differ in Th17, NK and Treg cells, which may be related to prognosis. TCM treatment may improve the level of B cells by utilizing strengthening spleen method, therefore enhancing humoral immunity. TCM treatment may reach Thl/Th2 balance regulation mainly through reducing Th2 cells, which strengthening spleen and nourishing kidney method has the most significant effect. Methods of strengthening spleen and nourishing kidney may show a two-way adjustment of Th17 cells, and ultimately achieve the level of Th17 cells in the body’s equilibrium.In future studies will explore the intrinsically links between TCM syndromes, genomics, immunology and metastasis and recurrence, and depict a series of features of advantages crowd in postoperative patients with colorectal cancer. We hope the researches can make more patients can benefit from TCM therapeutic medicine to achieve the best living conditions. |
PDF Full Text Request