Research Of Aspirin To The Risk And Prognosis Of Multiple Myeloma

Background and purpose:Aspirin,also known as Acetylsalicylic acid(ASA),is a commonly used non-steroidal anti-inflammatory drug(NSAID),which has anti-inflammatory and analgesic effects.It is not only used in the treatment of respiratory tract infections,fever,headache and rheumatic diseases,but also in the prevention of cardiovascular and cerebrovascular diseases.Relevant research results show that its mechanism of action is to effectively inhibit the activity of cyclooxygenase(COX)and the synthesis of prostaglandin(PG).ASA can also inhibit the synthesis of prostaglandin(PG),and the gastric mucosa loses the protective barrier of prostaglandin,resulting in gastroduodenal ulcer and bleeding.Recent studies have shown that ASA can reduce the incidence and mortality of rectal cancer,ovarian cancer,colon cancer and pancreatic cancer.While anti-cancer,ASA has lower toxicity and side effects,and its safety is significantly higher than other anti-cancer drugs.At present,the exact mechanism of ASA anti-tumor is not very clear.There are many reports of ASA anti-tumor effect in solid tumors,but few studies in hematological malignancies,and the research is focused on experimental studies,and few clinical studies.The experimental results show that ASA can induce apoptosis of human myeloma cells(MM1.S),and its mechanism is to induce apoptosis of myeloma cells through death receptor and mitochondria.In clinical studies,only Birmann BM reported that aspirin did not increase the risk of multiple myeloma in non-steroidal anti-inflammatory drugs,but there was no relevant clinical study in China.In this study,epidemiological investigation was conducted to explore the impact of ASA on the risk and prognosis of multiple myeloma by combining clinical and experimental methods.Method:1.To observe the correlation between aspirin and multiple myeloma:A matched case-control study was designed to collect 120 patients with multiple myeloma diagnosed in Ji'an area as matched cases with the same sex and age(+3years old)and 360 elderly people living nearby as the control group according to 1:3matching.The direct family members of multiple myeloma cases and other cancer patients were excluded.A unified questionnaire was used to collect the demographic characteristics,living environment,history of aspirin use(defined as at least one tablet per week for more than half a year),disease and family history of the subjects.Logistic risk regression model was used to estimate the adjusted ratio(OR)of aspirin to multiple myeloma risk and its 95%confidence interval(95%CI).The above analysis was completed by SPSS18.0 software package.The equilibrium and correlation between the general demographic characteristics of the case group and the control group were analyzed by X~2 test.The P value was the result of bilateral test,and the test level was 0.05.2.To study the antineoplastic effect of aspirin in multiple myeloma:120 patients diagnosed as multiple myeloma were divided into control group(routine treatment group)and experimental group(aspirin+routine treatment group).The experimental group took aspirin produced by Bayer Company of Germany(100mg/tablet).Beta 2microglobulin,LDH,plasma cell ratio and WT1 were observed before and after treatment for six months.This study was in line with medical ethics and informed consent was signed before treatment.3.Effect of aspirin on cell cycle and apoptosis in multiple myeloma:The effects of aspirin,thalidomide and dexamethasone on cell cycle and apoptosis of multiple myeloma cell lines were detected by MTT,cloning and flow cytometry.4.Effect of aspirin on immune function of multiple myeloma:Forty-nine MM patients admitted to the Department of Hematology,Hospital Affiliated to Jinggangshan University from January 2008 to December 2017 were selected.Among them,18 were newly diagnosed,with an average age of 63 years.They were divided into four groups:chemotherapy,chemotherapy+aspirin,dexamethasone+bortezomib,dexamethasone+bortezomib+aspirin.The expressions of CD4,CD8,CD25,CD11c,CD123 and intracellular IL-4,INF-gamma were detected before and after treatment.The ratio of T lymphocyte subsets and the regulation of T cell changes were observed.Result:1.Frequency and duration were negatively correlated with the morbidity.The longer the duration,the higher the morbidity(OR<1).2.Patients in the treatment group were given aspirin in the routine treatment of VAD.The results showed that the treatment group had better serum WT1,beta 2-m,fine ratio of bone marrow plasma and survival than the control group.3.Aspirin,Dex,Tha,Dex+Tha and Aspirin+Tha had significant effects on the proliferation of MM1.S cells treated with aspirin compared with the blank control group.The proportion of G1 phase and S phase in aspirin combined with thalidomide group decreased significantly,and increased significantly compared with other groups(P<0.05).The apoptotic rate was significantly increased in the combination group of dexamethasone and thalidomide,aspirin and thalidomide,and the effect of inducing apoptosis was more significant than that of single drug.4.The proportion of CD4+/CD8+in newly diagnosed MM patients decreased or reversed,and increased after chemotherapy.The results showed that the number and proportion of T lymphocyte subsets in MM patients were abnormal,and the proportion of T lymphocyte subsets recovered after chemotherapy.The results showed that chemotherapy or bortezomib could increase the ratio of CD4+/CD8+,DC1/DC2,Th1/Th2,and the ratio of Th1/Th2 increased more obviously after aspirin,the difference was statistically significant(P<0.05).Conclusion:1.Aspirin may reduce the risk of MM.2.Aspirin can enhance the sensitivity of MM to conventional chemotherapy drugs such as bortezomib and thalidomide.3.Compared with thalidomide combined with dexamethasone,thalidomide combined with aspirin maintenance therapy has lower side effects on MM.4.Aspirin combined with conventional chemotherapy is beneficial to improve the immune function of patients with MM.