Effect of Aspirin on G0/G1 Cell Cycle Arrest and microRNA Signatures in Pancreatic Adenocarcinoma Cells.

BACKGROUND/AIM: Anti-inflammatory drugs, such as aspirin, have attracted attention as anticancer agents that can be applied to standard chemotherapy for pancreatic cancer. This study aimed to examine the antitumour effects and possible fundamental mechanisms of aspirin in pancreatic cancer cells. MATERIALS AND METHODS: We appraised the antitumour effects of aspirin on cell proliferation and tumour growth, cell cycle distribution, apoptosis, signalling pathways, angiogenesis-related proteins, and phosphorylated receptor tyrosine kinases (p-RTKs) and identify miRNAs associated with its antitumour effects. RESULTS: Aspirin inhibited cell proliferation in pancreatic cancer cell lines and induced G0/G1 cell cycle arrest by decreasing the expression of cyclin D1. Aspirin inactivated glycogen synthase kinase (GSK)-3ß but had no effect on the p38 mitogen-activated protein kinase (MAPK) pathway, p-RTKs, or angiogenesis-related molecules. Aspirin treatment statistically increased the expression of 274 miRNAs in PANC-1 cells and 30 miRNAs in PK-8 cells and suppressed the expression of 294 miRNAs in PANC-1 cells and 13 miRNAs in PK-8 cells. CONCLUSION: Aspirin inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest. Aspirin also inactivated GSK-3ß but not the p38 MAPK pathway. Thus, aspirin may be used in combination with chemotherapeutic agents for pancreatic cancer.

Characterization of Cisplatin Effects in Lenvatinib-resistant Hepatocellular Carcinoma Cells.

BACKGROUND/AIM: Drug resistance to molecular targeted agents, such as lenvatinib, is an important issue. The aim of this study was to explore the mechanism of lenvatinib resistance and to investigate potential drugs that may improve the treatment of lenvatinib-resistant (LR) hepatocellular carcinoma (HCC). MATERIALS AND METHODS: LR cells were developed by long-term culture under lenvatinib exposure. We analyzed the biological characteristics of LR cells in vitro, and investigated the antitumor effects and endogenous mechanisms of cisplatin in LR cells. RESULTS: The proliferative potential of LR cells was enhanced by activation of ERK signaling and changes in several miRNAs. Cisplatin inhibited cell proliferation of LR cells and induced G2/M cell cycle arrest. Furthermore, cisplatin triggered the DNA damage response, via the ATM/ATR-Chk1/Chk2 signaling pathway. CONCLUSION: Proliferation of LR cells was induced upon ERK signaling activation. Cisplatin exerted antitumor effects in LR cells and was involved in the regulation of miRNAs associated with drug resistance.

Telomerase Reverse Transcriptase Promoter Mutations in Human Hepatobiliary, Pancreatic and Gastrointestinal Cancer Cell Lines.

BACKGROUND/AIM: The promoter region of the telomerase reverse transcriptase (TERT) gene is a regulatory element capable of affecting TERT expression, telomerase activity, and telomerase length. Mutations within the TERT promoter region are the most common mutations in many cancers. In this study, we characterized the TERT promoter mutation status in hepatobiliary, pancreatic, and gastrointestinal cancer cell lines. MATERIALS AND METHODS: TERT promoter mutation status was assessed by digital PCR in 12 liver cancer, 5 cholangiocarcinoma (CCA), 12 pancreatic cancer, 17 gastrointestinal cancer, and 3 healthy control cell lines. RESULTS: The C228T promoter mutation was detected in 9 liver cancer lines, and the C250T TERT mutation was detected in 1 oesophageal squamous cell carcinoma line. CONCLUSION: The C228T promoter mutation is specific to liver cancer cell lines among various gastrointestinal cancer cell lines. These data will contribute to future research on the tumorigenic mechanisms and clinical use of digital PCR to detect mutations.

Repeated balloon inflation under low pressure may reduce serious adverse events during endoscopic papillary large balloon dilation.

Highlight Kamada and colleagues devised a new technique for effective endoscopic papillary large balloon dilation without high balloon pressure. Advantages of the technique include the prevention of unintentional over-pressurization of the balloon by limiting the balloon inflation pressure and reduced risk of pancreatitis due to continuous pancreatic duct obstruction.

[Disorder of Gastric Myoelectric Activity in Patients with Cerebral Infarction:Electrogastrographic Assessment].

In this study, gastric myoelectric activity in patients with acute cerebral infarction was investigated using electrogastrography. The patients were divided into four groups; those with mild brainstem infarction(group A, n=13, men:8, women:5, 75±2 years old), severe brainstem infarction(group B, n=6, men:4, women:2, 79±4 years old), mild non-brainstem infarction(group C, n=14, men:7, women:7, 76±3 years old), and severe non-brainstem infarction(group D, n=9, men:3, women:6, 87±2 years old). In group B, the% ratio of normogastria(2.4-3.6 cycles per minute)was significantly lower in the fasting period. The dominant power(DP)significantly increased after the meal in group C, but did not in group A, compared to before the meal. The DP increased in all patients in group C after the meal, whereas it increased in only five of ten patients in group A. The possibility of gastric dysfunction should be considered in patients with brainstem infarction.