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.

Interaction between odor and taste information creates flavor perception. There are many possible determinants of the interaction between odor and taste, one of which may be the somatic sensations associated with breathing. We assumed that a smell stimulus accompanied by inhaling or exhaling enhances taste intensity if the order is congruent with natural drinking. To present an olfactory stimulus from the identical location during inhalation and exhalation, we blocked the gap between the tube presenting the olfactory stimulus and the nostril. Participants breathed and ingested the solution according to the instructions on the screen and evaluated the solution’s taste intensity. Vanilla odor enhanced the sweet taste in both retronasal and orthonasal conditions when the order of stimuli was congruent with natural drinking, but it did not do so in either condition when they were incongruent. The results suggest that breathing is a determinant of odor–taste interaction. The methods of presenting olfactory stimuli used in this study were compared and discussed in relation to those used in previous studies. Odor-induced taste enhancement depends on the time order of smell with breathing and taste congruency in natural drinking. Taste enhancement was induced by odor in both conditions by minimizing differences in odor presentation between them.

No abstract

Abstract. Background/Aim: Gemcitabine (GEM) Pancreatic cancer shows one of the worst prognoses among all malignant tumors since it progresses quickly and is difficult to diagnose at an early stage. Advances in chemotherapy are considered to be important for improving the prognosis of unresectable cases.Burris et al.(1) reported that gemcitabine (GEM) can significantly prolong survival in comparison to 5-FU for unresectable pancreatic cancer. Recently, FOLFIRINOX (L-OHP, CPT-11, 5-FU, LV) therapy (2) and GEM combined with nab-paclitaxel therapy (3) were shown to prolong survival. FOLFIRINOX was associated with strong toxicity, because it has not been established whether the combination therapy can be safely administered. It is thought that GEM based-chemotherapy will also be a key to the treatment of unresectable pancreatic cancer. It has been reported that recent advances in genetic analysis technology have revealed the factors involved with GEM sensitivity in pancreatic cancer cells (4, 5), and tailored therapies are expected.We identified GEM resistance-related proteins in pancreatic cancer by a proteomic analysis. We compared the expression levels of proteins in GEM-resistant pancreatic cancer cell lines with the expression in GEM-sensitive cell lines using twodimensional electrophoresis and liquid chromatography-mass spectrometry. Among them, the expression of Heat shock protein 27 (HSP27) was found to be increased in the GEMresistant cell line. Furthermore, we confirmed that GEM sensitivity was restored when the HSP27 expression in the GEM-resistant cell line was reduced (6, 7). Additionally, we clarified that the expression of phosphorylated HSP27 (p-HSP27) increased in the GEM-resistant cell line (8).In addition, the ability to predict the treatment effects using endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) samples may help in the selection of appropriate medicines for unresectable pancreatic cancer.No previous studies have evaluated the rates of HSP27 and p-HSP27 expression in pancreatic cancer cells from EUS-FNA samples. The purpose of this study was to evaluate the rates of HSP27 and p-HSP27 expression in EUS-FNA samples, and to demonstrate their association with GEM sensitivity. Materials and Methods Subjects, Examination itemsThe comparison of the rates of HSP27 expression in the EUS-FNA samples and the resected specimens. We compared the rates of HSP27 expression in EUS-FNA samples and resected specimens and evaluated the relationship with the resected specimens. The study population included 19 patients who had been diagnosed with 637 This article is freely accessible online.Correspondence to: Michitaka Kawano,