The Research Of The Advanced Primary Hepatic Carcinoma Interfered By Arsenictrioxide Through Hepatic Arterial Infusion Combined With The Traditional Chinese Medicine

Specialty: Clinical combination of TCM with Western medicineAuthor: Huang Hai-fuTutor: Professor Zhou Dai-hanObjective: To observe the clinical effect of Arsenictrioxide treating the advanced primary hepatic carcinoma through hepatic arterial infusion by the simple random clinical trial. To approach preliminarily Arsenictrioxide influencing the level of CyclinD1 and P27 protein in the hepatic carcinoma cell, disclose the mechanism of Arsenictrioxide affecting hepatic carcinoma cell cycle by vitro cell experiment.Methods: (1)Experiment part:â‘ Putting the log phase growth HepG2 cell suspension (concentration is 3×10⁵/ml) into the six-holes cell culture plate, and set up 4 groups: blank group, low-concentrationArsenictrioxide (1.0mg/L) group, mid-concentration Arsenictrioxide (1.5mg/L) group, high-concentration Arsenictrioxide (2.0mg/L) group. Then add the 0.5 ml calf serum containing the above-mentioned concentrationArsenictrioxide respectively.â‘¡Collecting the cell sample acted by the Arsenictrioxide after 72h.â‘¢Detecting the expression of CyclinDland P27 protein in the hepatic carcinoma cell by the immunohistochemistry SABC method and surveying the cells' cycle distribution by flow cytometer (FCM).(2) Clinical part: Dividing the 40 patients, whoare satisfied with the research standards, into the treatment group and the control group evenly. The patients in treatment group receive the treatment of Arsenictrioxide through hepatic arterial infusion combined with using Chinese traditional medicine by differentiation of symptoms and signs. The control group patients receive only using Chinese traditional medicine by differentiation of symptoms and signs. One week before and after the course of treatment, Observing the tumor objective remission rate, alpha fetoprotein (AFP) in blood serum, clinical symptoms relief, the quality of life, progress free survival time (PFST), medial survival time (MST), and etc. The treatment group also should be observed the probable adverse effect dynamic. Results: (1) Experiment part: In the HepG2 cells, which are affected by Arsenictrioxide 72 hours later, the level of CyclinD1 is obviously descended, while the level of P27 protein is upgrade obviously. These depend on concentration when the Arsenictrioxide' s concentration scope is from 1.0mg/L to 2.0mg/L. And the result of flow cytometer display that the generation cycle distribution is mainly stopped at the G₁ stage.(2) Clinical part:â‘ In the treatment group, 5 patients got PR, 11 got NC, and 4 were progress. The effective ratio (CR+PR) is 25%, while it is 15% in the control group. But there is not statistical significance between the two groups (P=0.362＞0.05) .â‘¡In the relief of symptoms, the effective ratio of treatment group is 50%, the control group is 60%, It display that the treatment has no superiority, and there is no statistical significance. In improving the personal state, the effective ratio are both 45% in the two groups. The P value is 0.494 by comparing the two groups each other in stabilizing patients' weight. So, the treatment group is no more superiority over the control group in the above aspects.â‘¢To the treatment group patients who had finished the treatment courses, the laboratory examinationpresentsthat the level of sero-AFP is apparent decline in the treatment group patients (P=0.045＜0.05=and the grade of Child—Pugh got better significantly (P=0.034＜0.05=. While to the control group, there is not statistically significant.â‘£We find there is some difference among the different TCMtypes of syndrome by the further observation. To the patients with the type of Splenic asthenia caused by excess of Liver-QI, Arsenictrioxide can stabilize the tumor and relieve the clinical symptoms effectively, and the therapeutic effect is good. While to the other two types, Liver phlegmasia with blood stasis and Yin deficiency of the Liver and Kidney, the therapeutic effect of Arsenictrioxide is not so ideal.⑤In the prostecdtive efficacy, patients in the treatment group, their PFST is 247±10.46 days, the survival rate of 3 months, 6months, one year is 90%, 84.7%, 32.8%respectively, and their MST is 276±11.51 days. However, patients in the control group, the corresponding figure are 178±9.56 days, 85%, 69.2%, 16.5%, and 202±11.18 days. There is statistically significant between the two groups.â‘¥In the adverse effect, individual occur abdominal distension, poor appetite and gentle hepatic function damage in the cause of receiving treatment of Arsenictrioxide injection. But these have no influence on the treatment. No serious adverse effect is found in the research. Conclusions: The Arsenictrioxide injection through hepatic arterial infusion combined with using Chinese traditional medicine by differentiation of symptoms and signs can efficiently stabilize the tumor in the treatment of the advanced primary hepatic carcinoma, prolong the patients' MST and PFST. Also, the adverse effects always occur gently and rarely. So, the Arsenictrioxide injection can be as one choice of the drug which are used in the treatment of the advanced primary hepatic carcinoma, the type by differentiation of symptoms and signs maybe is one of factors which can influence the clinical effect of the Arsenictrioxide. At the same time, our vitro experiment indicate incipiently that the mechanism of Arsenictrioxide affect the HepG2 cell cycle maybe is it can make the Cyclinel declined and P27 protein rise. It target at the restriction point of G₁-S, make the HepG2 cell cannot go through he restriction point of G₁-S to proliferate and stop the hepatic cell on the G₁ stage, then achieve to inhibit the hepatic cell proliferation.