Objectives Statins and calcium channel blockers have been proven beneficial toward improvement of endothelial function. The aim of this study was to compare the effect of combination therapy of statin and calcium channel blocker with solo treatment in patients with cardiac syndrome X. Methods and resultsSixty-eight patients with cardiac syndrome X were divided randomly into three groups: fluvastatin (40 mg/day, n = 23), diltiazem (90 mg/day, n = 22), and combination of fluvastatin (40 mg/day) and diltiazem (90 mg/day, n = 23). At the end of 90 days, the coronary flow reserve was improved in the three groups (fluvastatin-treated group: 23.2%; diltiazem-treated group: 12.4%; fluvastatin + diltiazem-treated group: 29.1%, all P < 0.05). The time to 1 mm ST segment depression increased significantly in the fluvastatin-treated group (from 241±97 to 410±140 s, P < 0.05), the diltiazem-treated group (from 258±91 to 392±124 s, P < 0.05), and the fluvastatin + diltiazem-treated group (from 250±104 to 446±164 s, P < 0.05). The improvement in coronary flow reserve and prolonged time to 1 mm ST segment depression in the combination treatment group were more remarkable than in those who received monotherapy. Combination therapy also induced a significant increase (35.6%, P < 0.05) in nitric oxide and an apparent reduction (48.7%, P < 0.05) in endothelin-1.Conclusion Combination treatment with fluvastatin and diltiazem is more effective on endothelial function and exercise tolerance than solo treatment in patients with cardiac syndrome X. The benefits of these drugs may be related to the elevation of nitric oxide and reduction of endothelin-1. Coron Artery Dis 25:40-44 c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Coronary Artery Disease 2014, 25:40-44

Whelming evidence has demonstrated that WW domain containing E3 ubiquitin protein ligase 1 (WWP1) participates in a wide variety of biological processes and is tightly related to the initiation and progression of many tumors. Currently, although mounting evidence supports a role of WWP1 in tumor promotion and tumorigenesis, the potential roles of WWP1 and its biological functions in gastric carcinoma are not fully understood. Here, we found that WWP1 messenger RNA (mRNA) and protein were highly expressed in gastric carcinoma tissues and cells. High WWP1 mRNA and protein levels were tightly related to differentiation status, TNM stage, invasive depth, lymph node metastasis, and poor prognosis in gastric carcinoma. Furthermore, WWP1 siRNA significantly decreased WWP1 protein level in MKN-45 and AGS cells; meanwhile, WWP1 depletion markedly inhibited tumor proliferation in vitro and in vivo, arrested cell cycle at G0/G1 phase, and induced cell apoptosis in MKN-45 and AGS cells. Most notably, WWP1 downregulation both inactivated PTEN-Akt signaling pathway in MKN-45 and AGS cells. Taken altogether, our findings suggest that WWP1 acts as an oncogenic factor and should be considered as a novel interfering molecular target for gastric carcinoma.

Identification of cytotoxic T lymphocyte (CTL) epitopes from tumor antigens is essential for the development of peptide vaccines against tumor immunotherapy. Among all the tumor antigens, the caner-testis (CT) antigens are the most widely studied and promising targets. PLAC1 (placenta-specific 1, CT92) was considered as a novel member of caner-testis antigen, which expressed in a wide range of human malignancies, most frequently in breast cancer. In this study, three native peptides and their analogues derived from PLAC1 were predicted by T cell epitope prediction programs including SYFPEITHI, BIMAS and NetCTL 1.2. Binding affinity and stability assays in T2 cells showed that two native peptides, p28 and p31, and their analogues (p28-1Y9 V, p31-1Y2L) had more potent binding activity towards HLA-A*0201 molecule. In ELISPOT assay, the CTLs induced by these four peptides could release IFN-γ. The CTLs induced by these four peptides from the peripheral blood mononuclear cells (PBMCs) of HLA-A*02+ healthy donor could lyse MCF-7 breast cancer cells (HLA-A*0201+, PLAC1+) in vitro. When immunized in HLA-A2.1/Kb transgenic mice, the peptide p28 could induce the most potent peptide-specific CTLs among these peptides. Therefore, our results indicated that the peptide p28 (VLCSIDWFM) could serve as a novel candidate epitope for the development of peptide vaccines against PLAC1-positive breast cancer.

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Cyclooxygenase‐2 is a promising target for cancer immunotherapy. Here, we designed the analogues p321‐9L and p321‐1Y9L (YLIGETIKL) from cyclooxygenase‐2‐derived native peptide p321. Then, we tested the binding affinity and stability of the analogues and their ability to elicit specific immune response both in vitro (from PBMCs of HLA‐A*02+ healthy donors) and in vivo (from HLA‐A2.1/Kb transgenic mice). Our results indicated that the activity of cytotoxic T lymphocytes induced by p321‐9L and p321‐1Y9L was more potent than that of p321. In conclusion, the epitope analogue, especially p321‐1Y9L, may be a good candidate which could be used to the immunotherapy of patients with tumours expressing cyclooxygenase‐2.