"Non Toxic Chemotherapy" Of Gastric Cancer The Effect Of Toremifene On Gastric Cancer: Clinical And Experimental Research

" Non Toxic Chemotherapy" of gastric cancerThe effect of Toremifene on gastric cancer:Clinical and experimental research.In 1983, Tokunaga and colleagues reported the presence of estrogen receptors (ER) in gastric cancer; as for the first time . Their findings quickly stimulated the interest of using Tamoxifen (TAM) as adjuvant treatment of gastric cancer in many countries. However the efficiency of this drug was not obvious to all. Tamoxifen has a number of side effects and also has been proved to have a carcinogenic effect .These disadvantages limited the clinical investigation of TAM on the treatment of gastric cancer. Toremifene (TOR) as a new generation of anti-estrogenic drug has less toxicity and is non-carcinogenic.This study aimed at the possibility of the clinical application and the mechanism of TOR in the treatment of gastric cancer in vitro and in vivo.Ⅰ Theoretical basis for the application of Toremifene(TOR)as new generation of anti-estrogenic drug in the treatment of gastric cancer.(phaseⅠ)Objective In this primary work, we investigated on the exact expression of estrogen receptor(ER) in gastric cancer in order to provide a clinical basis for the application of Toremifene as a new generation of anti-estrogenic drug in the treatment of gastric cancer. Method ER has been detected immunohistochemically in 349 cases of gastric adenocarcinoma. Avidin-Biotin-peroxidase Complex (ABC) method was used in 299 cases and the two- steps method in 50 cases.Also expression of p53 and PCNA have been investigated simultaneously. Result ER expression was 2.3% (7/299) and 0%(0/50) respectively. p53 expression was 37.1%(111/299) and 46% (23/50) respectively. PCNA expression was 94.3%(282/299) and 96%(48/50) respectively. Conclusion Gastric cancer cells could express estrogen receptors, with quantitative and qualitative changes. However our result showed that the exact value of ER expression in this cancer is very low. We think that the anti-cancer effects of both Tamoxifen (TAM) and Toremifene on gastric adenocarcinoma would be worthy of further investigation.Ⅱ In vitro screening test of the biological activity of TOR on gastric carcinoma(phaseⅡ)Objective We observed the selective inhibition effect of TOR at different concentration on: SGC-7901, MKN-28 and MKN-45, three proliferative human gastric adenocarcinoma cell line .Method According to the growth rate of the cells, a logarithmic growth period cancer cells were selected and inoculated in the 96 spores of lamina culture at 90μl/spore. The drug was added at 10μl/spore after paste growth for 24 hours.The screening test was done following the Sulforhodamine B(SRB) protein coloration method.One hundred and fifty micro-litre(μl )tris solution was added finally, and the A values were measured under a wavelength of 515nm.Then cancer cells growth inhibition rate were calculated following a formula .Result According to the standard result, the inhibition rate of TOR at the concentration of 10-5 mol/l on the 3 cells line was < 85%,demonstrating that TOR has no effect on the growth and proliferation of these 3 gastric adenocarcinoma cells line . However the result showed that at the concentration of 10-4 mol/l, the cells were inhibited at the rate of 93.7%, 92.3% and 95.1% respectively.Conclusion At a low concentration, TOR has no potential effect in vitro on the growth of SGC-7901, MKN-28 and MKN- 45 three human gastric cancer cells line. But at high concentration TOR could have a potent gastric cancer cell toxicity. However the dilemma whether this concentration of TOR can be tolerated in vivo or not remains to be solved out. Ⅲ Experimental treatment of human gastric cancer SGC-7901 and MKN-45 nude mice by Toremifene (phase Ⅲ). Objective The experimental treatment effect of TOR was assessed on the human gastric adenocarcinoma implanted in nude mice.Method The specimen with 1.5 mm3 in size were cut from the prosperous development phase tissu...