Antitumor Effect of Galectin-9 on Cell Proliferation and Tumor Growth of Human Duodenal Adenocarcinoma Cells.

BACKGROUND/AIM: Galectin-9 (Gal-9) induces tumor cell apoptosis in lymphoma and other malignant cell types. Duodenal adenocarcinoma is a rare malignancy, and there are insufficient data to determine a standard therapeutic approach. Here, we investigated the antitumor effect of Gal-9 in HuTu-80 duodenal adenocarcinoma cells. MATERIALS AND METHODS: Cell proliferation was examined in HuTu-80 cells using a Cell Counting Kit-8 assay. Cell cycle analysis, apoptosis array, and microRNA expression analysis were performed to identify the effect of Gal-9 on HuTu-80 cells. The antitumor effect of Gal-9 was also examined using xenograft mouse models. RESULTS: Gal-9 suppressed the proliferation of HuTu-80 via blockade of the G0 to G1 cell cycle transition. This blockade was accompanied by a strong decrease in cyclin D1 and phosphorylated Rb, suggesting a G1 arrest. Additionally, Gal-9 induced apoptosis, and the expression of cleaved caspase-3 was increased in Gal-9-treated HuTu-80 cells according to the apoptosis array. MiRNA microarrays revealed that Gal-9 altered the expression of miRNAs in HuTu-80 cells. CONCLUSION: These data demonstrate the therapeutic potential of Gal-9 and provide molecular mechanistic insights into its antitumor effect in HuTu-80 cells.

Use of endoscopic gallbladder stenting and biliary scintigraphy for diagnosis of gallbladder dyskinesia: a case report.

A 40-year-old woman visited our hospital with a several-year history of right hypochondriac pain and vomiting after eating. She had been treated for functional dyspepsia, with no improvement in her symptoms. No gallstones were detected on imaging tests, but papillary insufficiency or dyskinesia of the gallbladder was suspected and biliary scintigraphy was performed. Biliary scintigraphy showed delayed excretion of radionuclides from the gallbladder and bile ducts into the duodenum. We initially suspected papillary dysfunction and performed endoscopic sphincterotomy, but there was no improvement in her symptoms. Biliary scintigraphy also showed delayed excretion of radionuclides, especially stagnation of radionuclides in the gallbladder. We suspected gallbladder dyskinesia and performed endoscopic gallbladder stenting, after which her symptoms disappeared and biliary scintigraphy showed improved excretion of radionuclides into the duodenum. Endoscopic gallbladder stenting may be useful for the diagnosis of gallbladder dyskinesia and for determining the efficacy of cholecystectomy.

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.

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.

Comparison of plastic stent versus metal stent in preoperative biliary drainage for pancreatic head cancer with neoadjuvant chemoradiotherapy.

BACKGROUND: While neoadjuvant chemotherapy and chemoradiotherapy (NACRT) for pancreatic head cancer are effective, preoperative endoscopic biliary drainage (EBD) is necessary for managing obstructive jaundice and cholangitis during the preoperative waiting period. Nevertheless, ideal choice of stent type is unclear. We compared plastic stents (PS) and metal stents (MS) in these situations. METHODS: We retrospectively studied 43 patients who successfully underwent preoperative EBD prior to NACRT for pancreatic head cancer at a single institution. We divided patients into PS (n = 22) and MS (n = 21) groups. The primary outcome was the rate of re-interventional drainage rate before surgery. Secondary outcomes were rates of EBD-associated and postoperative complications and total costs in the pre- and perioperative periods. RESULTS: The re-intervention rate was significantly greater in the PS group than in the MS group (95% vs 4.8%, respectively, P < 0.05). EBD-associated and postoperative complications were significantly less common in the MS group (P < 0.05). The average total preoperative medical costs were significantly lower in the MS group (PS vs MS: 528,597 vs 395,891 JPY, P = 0.004). CONCLUSIONS: MS can be the first choice for EBD in patients undergoing NACRT for pancreatic head cancer. MS may be less costly overall.

The Effect of Gemcitabine on Cell Cycle Arrest and microRNA Signatures in Pancreatic Cancer Cells.

BACKGROUND/AIM: Gemcitabine, an inhibitor of DNA synthesis, is the gold standard chemotherapeutic agent for pancreatic ductal adenocarcinoma (PDAC). MicroRNAs (miRNAs) play critical roles in cancers, including PDAC. However, less is known about the effect of gemcitabine on PDAC cells and miRNA expression in PDAC. We evaluated the effect of gemcitabine on the cell cycle of PDAC cells in vitro and in vivo and on the miRNA expression profile. MATERIALS AND METHODS: Effects of gemcitabine on PK-1 and PK-9 cell growth were evaluated using a cell counting kit-8 assay. Xenografted mouse models were used to assess gemcitabine effects in vivo. RESULTS: Gemcitabine inhibited the proliferation and tumour growth of PK-1 cells, and induced S phase cell cycle arrest. Numerous miRNAs were altered upon gemcitabine treatment of PK-1 cells and xenograft models. CONCLUSION: Altered miRNAs may serve as potential therapeutic targets for improving the efficacy of gemcitabine in PDAC.

Antihypertensive drug telmisartan suppresses the proliferation of gastric cancer cells in vitro and in vivo.

Gastric cancer is one of the most common malignancies diagnosed worldwide. Telmisartan, an angiotensin receptor blocker (ARB), suppresses the proliferation of cancer cells and the growth of tumors through an unknown mechanism. To identify the mechanism, the present study was designed to evaluate the effects of telmisartan on gastric cancer cell lines and tumors in vitro and in vivo and the associated signaling molecules were identified. It was shown here that telmisartan suppressed the proliferation of the cultured human gastric cancer cell lines MKN74, MKN1 and MKN45 as detected in the CCK­8 assay. In a mouse xenograft model of gastric cancer, telmisartan suppressed tumor growth by arresting the cell cycle at the G0/G1 phase through inhibition of the expression of cyclin D1, the catalytic subunit of cyclin dependent kinase 4 (CDK4), as well as the phosphorylation of the tumor suppressor retinoblastoma (pRb) protein as detected by western blotting. Notably, telmisartan did not induce apoptosis, as indicated by consistent levels of caspase­cleaved keratin 18 in MKN74 cells. Furthermore, telmisartan inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and increased the levels of the angiogenesis­related protein tissue inhibitor of metalloproteinase­1 (TIMP­1). Analyses of microarrays revealed that telmisartan altered the expression of miRNAs in MKN74 cells. In conclusion, telmisartan suppressed the proliferation of human gastric cancer cells by inducing cell cycle arrest.

Metformin Inhibits Proliferation and Tumor Growth of QGP-1 Pancreatic Neuroendocrine Tumor Cells by Inducing Cell Cycle Arrest and Apoptosis.

BACKGROUND/AIM: Pancreatic neuroendocrine tumors (pNETs) are rare pancreatic neoplasms, and therapeutic options for pNETs are limited. Metformin is an anti-hypoglycemic drug that appears to have anticancer effects. However, little is known about the effect of metformin on pNETs. In this study, we investigated the anti-proliferative effect of metformin on a human pNET cell line. MATERIALS AND METHODS: The anti-proliferative properties of metformin were evaluated in QGP-1 and NCI-H727 cells using a cell counting kit-8 assay. Xenograft mouse models were used to assess the tumor effect in vivo. RESULTS: Metformin inhibited the proliferation and anti-tumor growth of QGP-1 cells, accompanied by their arrest during the cell cycle at the G0/G1 phase. Immunohistochemical analysis of tumor tissues revealed down-regulation of cyclin D1 and proliferating cell nuclear antigen in the metformin-treated group. Additionally, metformin induced apoptosis, and the expression of survivin and claspin were decreased in metformin-treated QGP-1 cells according to the apoptosis array. Furthermore, the angiogenic related protein TIMP-1 was down-regulated, and its miRNA expression was altered by metformin in QGP-1 cells. CONCLUSION: Taken together, our study demonstrated the therapeutic potential of metformin and provides molecular mechanistic insights into its anti-tumoral effect on pNETs. This study is the first one describing anti-tumoral effects in pNETs.

Telmisartan Inhibits Cell Proliferation and Tumor Growth of Esophageal Squamous Cell Carcinoma by Inducing S-Phase Arrest In Vitro and In Vivo.

Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy. Telmisartan, an angiotensin II type 1 (AT1) receptor blocker (ARB) and a widely used antihypertensive, has been shown to inhibit proliferation of various cancer types. This study evaluated the effects of telmisartan on human ESCC cell proliferation in vitro and in vivo and sought to identify the microRNAs (miRNAs) involved in these antitumor effects. We examined the effects of telmisartan on three human ESCC cell lines (KYSE150, KYSE180, and KYSE850). Telmisartan inhibited proliferation of these three cell lines by inducing S-phase arrest, which was accompanied by decreased expression of cyclin A2, cyclin-dependent kinase 2, and other cell cycle-related proteins. Additionally, telmisartan reduced levels of phosphorylated ErbB3 and thrombospondin-1 in KYSE180 cells. Furthermore, expression of miRNAs was remarkably altered by telmisartan in vitro. Telmisartan also inhibited tumor growth in vivo in a xenograft mouse model. In conclusion, telmisartan inhibited cell proliferation and tumor growth in ESCC cells by inducing cell-cycle arrest.