ABSTRACT
INTRODUCTION: We previously developed a novel methylation assay, the combined restriction digital PCR (CORD) assay, consisting of treatment of DNA with methylation-sensitive restriction enzymes and droplet digital PCR. METHODS: In this study, we assessed the diagnostic performance of serum methylated Homeobox A1 (mHOXA1) and methylated somatostatin (mSST) using the CORD assay in combination with CA19-9 for pancreatic cancer using serum samples from 82 healthy individuals, 13 patients with benign pancreatic disease, 3 patients with branched-duct intraductal papillary mucinous neoplasm, and 91 patients with pancreatic cancer. RESULTS: For the single marker tests, sensitivity for all stages of pancreatic cancer, stage I cancer, and specificity were, respectively, 71.4%, 50.0%, and 94.9% for CA19-9; 51.6%, 68.8%, and 90.8% for mHOXA1; and 50.1%, 68.8%, and 94.9% for mSST. Those for the combined marker tests were, respectively, 86.8%, 81.3%, and 85.7% for combined mHOXA1 and CA19-9; 86.8%, 87.5%, and 89.8% for combined mSST and CA19-9; and 89.0%, 87.5%, and 85.7% for all three markers combined. CONCLUSION: The combination of mHOXA1 and mSST with CA19-9 appears to be useful to detect pancreatic cancer even at an early stage.
Subject(s)
CA-19-9 Antigen , Pancreatic Neoplasms , Humans , Biomarkers, Tumor/genetics , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Somatostatin , Pancreatic NeoplasmsABSTRACT
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, next-generation 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.
Subject(s)
Cell Movement/drug effects , Deferasirox/pharmacology , Iron Chelating Agents/pharmacology , Neoplasm Invasiveness/prevention & control , Pancreatic Neoplasms/pathology , Cell Line, Tumor , Cell Survival/drug effects , Humans , In Vitro Techniques , Microarray Analysis , Pancreatic Neoplasms/metabolism , cdc42 GTP-Binding Protein/metabolism , rac1 GTP-Binding Protein/metabolism , Pancreatic NeoplasmsSubject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Klatskin Tumor , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic , Cholangiocarcinoma/complications , Cholangiocarcinoma/diagnostic imaging , Drainage , Endosonography , Humans , Klatskin Tumor/complications , Klatskin Tumor/surgery , Stents , Ultrasonography, InterventionalABSTRACT
Herein we report the case of a patient with multiple glucagonomas that have been precisely described with endoscopic ultrasound. A 36-year-old woman was referred to our hospital for computed tomography investigation of multiple pancreatic masses. Physical examination was unremarkable; on contrast-enhanced computed tomography, mass lesions were evident in the head, body, and tail of the pancreas. The mass in the pancreatic head was poorly demarcated and exhibited a faint contrast effect, the one in the pancreatic body was a cystic lesion, and the one in the pancreatic tail was hypervascular. Blood investigations showed that serum glucagon was abnormally high at 7670 pg/ml; glucose tolerance was not impaired. There was no family history that suggested multiple endocrine neoplasia type 1 or von Hippel-Lindau disease. Endoscopic ultrasound revealed that there were additional masses, which were scattered isoechoic to hyperechoic lesions a few millimeters in size. Ultrasound-guided fine needle biopsy of the lesion in the pancreatic tail resulted in a diagnosis of a neuroendocrine tumor. Based on these pathologic findings, we performed a total pancreatectomy. A large number of nodules with tumor cells were evident in all cut surfaces of the surgical specimen. Immunostaining was positive for chromogranin A and glucagon, and glucagonoma was therefore diagnosed. It is conceivable that attenuated glucagon action could have contributed to the development of the multiple glucagonomas.
ABSTRACT
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.
Subject(s)
Odorants , Taste , Humans , Smell , Taste Perception , RespirationABSTRACT
BACKGROUND: The best palliation for double obstruction (duodenal obstruction with biliary obstruction) remains unclear. We aimed to compare outcomes of duodenal stenting (DuS) with gastrojejunostomy (GJ) and identify factors associated with survival time and time to recurrent biliary obstruction (TRBO). METHODS: Patients who underwent DuS or GJ combined with biliary stenting for double obstruction due to unresectable malignancy were retrospectively enrolled. RESULTS: In total, 111 patients were included; 84 underwent DuS, and 27 underwent GJ. The weighted survival time of the DuS group was significantly shorter than that of the GJ group (86 days vs 134 days, P < 0.01). Although the weighted TRBO was not significantly different between the two groups, when limited to patients with distal duodenal obstruction, the weighted TRBO was significantly longer in the DuS group than in the GJ group (207 days vs. 32 days, P < 0.01). GJ for distal duodenal obstruction was identified as the factor with the highest hazard ratio and was associated with a shorter TRBO (hazard ratio 8.5, P < 0.01). CONCLUSIONS: Regarding survival time, GJ should be considered the primary treatment for patients with double obstruction. However, for patients with distal duodenal obstruction, DuS should be considered because GJ may be a risk factor for a shorter TRBO.
Subject(s)
Cholestasis , Duodenal Obstruction , Gastric Bypass , Stents , Cholestasis/complications , Cholestasis/surgery , Duodenal Obstruction/etiology , Duodenal Obstruction/surgery , Gastric Bypass/adverse effects , Humans , Palliative Care , Retrospective Studies , Stents/adverse effectsABSTRACT
BACKGROUND/AIM: Gemcitabine (GEM) sensitivity can help select the appropriate treatment for pancreatic cancer. We examined the association between HSP27 expression and GEM sensitivity. MATERIALS AND METHODS: A total of 19 patients with unresectable pancreatic cancer who underwent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) were enrolled and treated with GEM alone. We measured the expression of heat shock protein 27 (HSP27) and phosphorylated HSP27(p-HSP27) in EUS-FNA samples and evaluated the effects of GEM treatment. RESULTS: The rate of GEM resistance was significantly higher in patients who showed overexpression of p-HSP27 (p<0.05). When we set the cut-off p-HSP27 (Ser82) detection rate at 51.6%, the group with a detection rate of >51.6% showed a significantly lower survival rate, and GEM was administered for a shorter period of time (p<0.05). CONCLUSION: It was suggested that the HSP27 expression in EUS-FNA samples was useful for predicting GEM sensitivity.
Subject(s)
Gene Expression , HSP27 Heat-Shock Proteins/genetics , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Aged , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Drug Resistance, Neoplasm/genetics , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Pancreatic Neoplasms/drug therapy , ROC Curve , Survival Analysis , Treatment Outcome , GemcitabineABSTRACT
OBJECTIVES: Iron 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. RESULTS: GEM+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. CONCLUSION: GEM+DFX has significant anticancer effects on pancreatic cancer cell through RR activity suppression. METHODS: BxPC-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.