64 Perindopril, captopril, losartan and valsartan significantly inhibited the tumor volume and lymphatic microvessel density resulting from implanting the human gastric cancer cell line SGC-7901 http://www.selleckchem.com/products/LBH-589.html into mice.65 In a large cohort study, Lever et al.62 demonstrated that RAS inhibitors have a chemopreventive effect in patients undergoing long-term treatment for hypertension. Diabetes patients taking ACE-I had a history of all cancer types at lower rates (10%) than non-users (10% vs 15%; OR: 0.59, 95%CI: 0.39–0.89).66 However, other epidemiological studies failed to demonstrate this effect.67–70 It should be noted that these latter studies suffered from limitations involving an older patient population

treated with ACE-I for shorter time periods. Thus, the discrepancy between these results may be accounted for by differences in treatment time, use of ACE-I/ARB, geographic locations, patient compliance, and dose. ACE-I and ARB treatment is associated with longer progression-free survival (PFS) and overall survival (OS) in advanced pancreatic cancer patients receiving gemcitabine.71 PFS and OS values for pancreatic cancer

patients were 8.7 and 15.1 months, respectively, for ACEI/ARB-treated YAP-TEAD Inhibitor 1 patients and 3.6 and 9.5 months, respectively, for the non-hypertension group.71 Moreover, patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy receiving either ACE-I or ARB had a 3.1-month longer median survival time than non-recipients (11.7 vs 8.6 months).72 ARB has cytostatic activity against hormone-refractory prostate cancer, as indicated by decreased prostate-specific see more antigen levels,73 and ACE-I in combination with vitamin K also suppresses hepatocellular carcinoma recurrence.74 To our knowledge, however, no report on gastric cancer has yet appeared. ACE-I and ARB may differentially influence oncogenesis because ACE-I blocks ACE-dependent AT1R and AT2R,

whereas ARB blocks ACE- and chymase-dependent AT1R and AT2R. In a hamster-sponge model, when both AngI and AngII were injected directly into the sponge, angiogenesis was enhanced. AngI-induced angiogenesis was inhibited by a chymase inhibitor, but not that due to AngII.75 These findings suggest the importance of chymase-dependent AngII generation in angiogenesis. This comprehensive literature review involving numerous studies suggests that RAS plays important roles in various aspects of gastric cancer progression related to H. pylori infection. Moreover, RAS’s influence on H. pylori-related gastric oncogenesis suggests that it should be a target for chemoprevention. RAS component inhibitors might reduce gastric cancer development, progression, and metastasis. We believe that our literature review has made a very clear and compelling case for intensive research on RAS and its relationship to gastric cancer.