Background: Pancreatic cancer is generally characterized with high levels of malignancy and poor prognosis. In addition, there are currently no effective therapeutic agents against the disease. However, apatinib which is a small molecular agent targeting the vascular endothelial growth factor receptor 2 (VEGFR-2), has been shown to generate favorable outcomes in gastric cancer. Therefore, the present study explored the effects of apatinib on pancreatic cancer. Methods:The activity of the ASPC-1 or PANC-1 cells was examined through colony formation assays, wound healing experiments as well as the Transwell and Western blot (WB) analyses. Additionally, axenograft model was established by subcutaneously injecting the ASPC-1 cells into nude mice. Microvessel density (MVD) and Ki-67 expression were examined through immunohistochemistry (IHC) and WB analyses. Results:The findings showed that treatment with either 10 or 20 μM of apatinib led to a decrease in the proliferation, migration and invasion of ASPC-1 and PANC-1 cells. Additionally, apatinib significantly hindered xenograft growth. Moreover, there was a decrease in Ki-67 expression and MVD, 21 days after treatment with apatinib. The results also showed that apatinib had no effect on the levels of the VEGFR-2, ERK1/2 and AKT proteins although there was a significant decrease in the expression of phosphate VEGFR2 (p-VEGFR2), phosphate AKT (p-AKT) and phosphate ERK1/2 (p-ERK1/2).Conclusions: Apatinib inhibits the proliferation and migration of pancreatic cancer cells, blocking growth and angiogenesis in transplanted tumors. In addition, the underlying mechanism may involve phosphorylation of the PI3K/AKT and ERK1/2/MAPKs signaling pathways.

Ras protein activator like 2 (RASAL2) has a cancer‐related function, but plays inconsistent roles in different malignancies. This project was designed to determine the role of RASAL2 in carcinogenesis in gastric cancer. The Cancer Genome Atlas data revealed high levels of RASAL2 in gastric cancer tissue, which was confirmed in clinical specimens of gastric cancer via real‐time quantitative PCR and western blotting assays. High RASAL2 was correlated with a reduced survival rate in gastric cancer patients. In gastric cancer cell lines, the silencing of RASAL2 restrained cellular proliferation, invasion and epithelial‐to‐mesenchymal transition, while enhancing chemosensitivity to cisplatin. Mechanistically, the silencing of RASAL2 was found to inhibit the activation of Yes‐associated protein 1 (YAP1), a pro‐oncogenic protein in gastric cancer, and decrease the expression of YAP1 target genes. The re‐expression of constitutively active YAP1 substantially reversed RASAL2‐silencing‐produced antitumor effects. Moreover, treatment with YAP1 inhibitors could diminish RASAL2‐overexpression‐evoked oncogenic effects in gastric cancer cells. Additionally, gastric cancer cells with RASAL2 silencing exhibited a reduced ability to form xenograft tumors in nude mice. Collectively, our data demonstrate that the silencing of RASAL2 has noteworthy antitumor effects in gastric cancer cells via the suppression of YAP1 activation. This project underscores a vital role of the RASAL2/YAP1 axis in gastric progression and indicates that targeting this oncogenic axis may be applied as a potential therapeutic option for gastric cancer.

Objective : Choriocarcinoma is a highly malignant epithelial tumor and primarily occurs in women of childbearing age, while it is extremely rare in postmenopausal women and only scattered cases have been reported worldwide. In addition, whether the prognosis scoring system for gestational trophoblastic neoplasm is suitable for postmenopausal women is still controversial and there is no consistent strategy for the treatment and management. Therefore, the aim of this study is to summarize and analyze the clinicopathologic features of choriocarcinoma in postmenopausal women to increase the awareness of this rare disease.Method : We retrieved the PubMed, Web of science, Embase, and CBM databases to search relevant published literatures, and then, the details of each patient's clinical and pathological characteristics were extracted and analyzed. Univariate log-rank tests were used to examine the association between clinicopathologic characteristics and progression-free survival (PFS) and overall survival(OS).Results : 33 patients, according to the given inclusion and exclusion criteria, were included in this study. The patients originated from different continents, with 55% located in Asia and 27% in North America.The mean age of these patients was 59 years (range 48-74years) and the mean age at menopause was 49.7 years (from 39 to 57 years). The median interval from antecedent pregnancy to diagnosis was 22 years(5-42years). The mean time of the duration of menopause of patients recorded relevant information was 9 years(1-26years).The mean β-HCG titer was 235,644 mIU/mL. 22 patients presented with abnormal vaginal bleeding, 4 with lesion-related pain. The site of primary lesions distribution relatively broad, mainly in uterus and lung. 29 patients were classified as high-risk disease. 22 patients underwent curative surgery with or without chemotherapy, 11 patients received only chemotherapy, and most chemotherapy regimens were EMA-CO.Stage of disease was significantly associated with both PFS and OS (P=0.007;P=0.040).The median follow-up time was 21 months, with 2 cases recurred, 2 progressed, and 5 died. The tumor were positive for HCG, CK, HPL,PLAP and EMA.Conclusion : We observed that abnormal vaginal bleeding and lesion-related pain are the most common presenting features of postmenopausal choriocarcinoma. The patients often have metastatic lesions, high level serum β-HCG, and classified to high-risk disease when diagnosed. Moreover, the prognosis in those patients are worse than those in reproductive period. As in patients with choriocarcinoma of childbearing age, stage is still the main prognostic factor.