Using CE-EUS to measure MN height provides a highly accurate method for differentiating benign from malignant BD-IPMN.

BackgroundIron is essential for cell replication, metabolism and growth. Because neoplastic cells have high iron requirements due to their rapid proliferation, iron depletion may be a novel therapeutic strategy for cancer. Deferasirox (DFX), a novel oral iron chelator, has been successful in clinical trials in iron-overload patients and has been expected to become an anticancer agent. However, no studies have investigated the effects of DFX on pancreatic cancer. This study aimed to elucidate the effects of DFX against pancreatic cancer.MethodsThe effects of DFX on cell cycle, proliferation, and apoptosis were examined in three human pancreatic cancer cell lines: BxPC-3, HPAF-II, and Panc 10.05. The effect of orally administered DFX on the growth of BxPC-3 pancreatic cancer xenografts was also examined in nude mice. Additionally, microarray analysis was performed using tumors excised from xenografts.ResultsDFX inhibited pancreatic cancer cell proliferation in a dose-dependent manner. A concentration of 10 μM DFX arrested the cell cycle in S phase, whereas 50 and 100 μM DFX induced apoptosis. In nude mice, orally administered DFX at 160 and 200 mg/kg suppressed xenograft tumor growth with no serious side effects (n = 5; average tumor volumes of 674 mm3 for controls vs. 327 mm3 for 160 mg/kg DFX, p <0.05; average tumor volumes of 674 mm3 for controls vs. 274 mm3 for 200 mg/kg DFX, p <0.05). Importantly, serum biochemistry analysis indicated that serum levels of ferritin were significantly decreased by the oral administration of 160 or 200 mg/kg DFX (n = 5; average serum ferritin of 18 ng/ml for controls vs. 9 ng/ml for 160 mg/kg DFX, p <0.05; average serum ferritin of 18 ng/ml for controls vs. 10 ng/ml for 200 mg/kg DFX, p <0.05). Gene expression analysis revealed that most genes in pancreatic adenocarcinoma signaling, especially transforming growth factor-ß1 (TGF-ß1), were downregulated by DFX.ConclusionsDFX has potential as a therapeutic agent for pancreatic cancer. Iron depletion was essential for the antiproliferative effect of DFX in a preclinical model, and DFX acted through the suppression of TGF-ß signaling.

BackgroundInflammatory fibroid polyps (IFPs) are rare mesenchymal lesions that affect the gastrointestinal tract. IFPs are generally considered benign, noninvasive lesions; however, we report a case of an invasive gastric IFP. To the best of our knowledge, this is only the second case report of an invasive gastric IFP.Case presentationA 62-year-old woman presented with complaints of epigastric pain and vomiting. Computed tomography showed a 27-mm, hyper-enhancing tumor in the prepyloric antrum. Upper endoscopy also showed a submucosal tumor causing subtotal obstruction of the gastric outlet. Because a gastrointestinal stromal tumor was suspected, distal gastrectomy was performed. Histopathological examination revealed spindle cell proliferation in the submucosal layer. The spindle cells had invaded the muscularis propria layer and extended to the subserosal layer. The tumor was finally diagnosed as an IFP based on immunohistochemical findings. No mutations were identified in the platelet-derived growth factor receptor alpha (PDGFRA) gene via molecular genetic analysis.Discussion and conclusionsAfter the discovery that IFPs often harbor PDGFRA mutations, these growths have been considered neoplastic lesions rather than reactive lesions. Based on the present case, IFPs might be considered not only neoplastic but also potentially invasive lesions.

ObjectivesIron is an essential element for cell proliferation and growth processes. We have reported that deferasirox (DFX), an oral iron chelator, showed antiproliferative activity against pancreatic cancer cells. This study aimed to elucidate the effects of combination of gemcitabine (GEM), standard chemotherapy for pancreatic cancer, and DFX in vitro and in vivo.ResultsGEM+DFX showed antiproliferative activity and induced apoptosis in pancreatic cancer cells in vitro. GEM+DFX suppressed xenograft tumor growth and induced apoptosis without any serious side effects compared with control, GEM, and DFX (average tumor volume: control 697 mm3 vs GEM 372 mm3, p < 0.05; GEM 372 mm3 vs GEM+DFX 234 mm3, p < 0.05). RRM1 and RRM2 protein levels were substantially reduced by DFX in BxPC-3 in vitro.ConclusionGEM+DFX has significant anticancer effects on pancreatic cancer cell through RR activity suppression.MethodsBxPC-3, a human pancreatic cancer cell line, was used in all experiments. Cellular proliferation rate was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay. Apoptosis was evaluated by flow cytometry and by measuring caspase 3/7 activity with luminescence assay. In the tumor xenografts in nude mice models, when five weeks after engraftment, drug administration began (day 0). After treatment for 21 days, the mice were sacrificed and the tumors were excised. Apoptotic cells in xenografts were evaluated by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay. Protein levels of ribonucleotide reductase (RR) subunit 1 (RRM1) and RR subunit 2 (RRM2) in BxPC-3 cells were assessed by western blot in vitro.

Background: Iron is required for cellular metabolism, and rapidly proliferating cancer cells require more of this essential nutrient. Therefore, iron regulation may well represent a new avenue for cancer therapy. We have reported, through in vitro and in vivo research involving pancreatic cancer cell lines, that the internal-use, nextgeneration iron chelator deferasirox (DFX) exhibits concentration-dependent tumour-suppressive effects, among other effects. After performing a microarray analysis on the tumour grafts used in that research, we found that DFX may be able to suppress the cellular movement pathways of pancreatic cancer cells. In this study, we conducted in vitro analyses to evaluate the effects of DFX on the invasive and migratory abilities of pancreatic cancer cells. Methods: We used pancreatic cancer cell lines (BxPC-3, Panc-1, and HPAF II) to examine the efficacy of DFX in preventing invasion in vitro, evaluated using scratch assays and Boyden chamber assays. In an effort to understand the mechanism of action whereby DFX suppresses tumour invasion and migration, we performed G-LISA to examine the activation of Cdc42 and Rac1 which are known for their involvement in cellular movement pathways. Results: In our scratch assays, we observed that DFX-treated cells had significantly reduced invasive ability compared with that of control cells. Similarly, in our Boyden chamber assays, we observed that DFX-treated cells had significantly reduced migratory ability. After analysis of the Rho family of proteins, we observed a significant reduction in the activation of Cdc42 and Rac1 in DFX-treated cells. Conclusions: DFX can suppress the motility of cancer cells by reducing Cdc42 and Rac1 activation. Pancreatic cancers often have metastatic lesions, which means that use of DFX will suppress not only tumour proliferation but also tumour invasion, and we expect that this will lead to improved prognoses.