• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3781-3789
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• 2012

Background: Pancreatic cancer is one of the most aggressive tumors with a dismal prognosis. The membrane cytoskeletal crosslinker Ezrin participates in several functions including cell proliferation, adhesion, motility and survival. There is increasing evidence that Ezrin is overexpressed in vast majority of malignant tumors and regulates tumor progression. However, its roles in pancreatic cancer remain elusive. Methods: Three pairs of specific Ezrin siRNAs were designed and synthetized and screened to determine the most efficient one for construction of a hairpin RNA plasmid targeting Ezrin. After transfection into the Panc-1 pancreatic cancer cell line, real-time quantitative PCR and Western blotting were performed to examine the expression of mRNA and protein. The MTT method was applied to examine the proliferation and the drug sensibility to Gemcitabine. Flow cytometry was used to assess the cycle and apoptosis, while capacity for invasion was determined with transwell chambers. Furthermore, we detected phosphorylated-Erk1/2 protein and phosphorylated-Akt protein by Western blotting. Results: Real-time quantitative PCR and Western blotting revealed that Ezrin expression was notably down-regulated at both mRNA and protein levels by RNA interference (P< 0.01). Proliferation was inhibited and drug resistance to gemcitabine was improved (P< 0.05). Flow cytometry showed that the proportion of cells in the G1/G0 phase increased (P< 0.01), and in G2/M and S phases decreased (P< 0.05), with no apparent differences in apoptosis (P> 0.05). The capacity for invasion was markedly reduced (P< 0.01). In addition, down-regulating Ezrin expression had no effect on phosphorylated-Akt protein (P>0.05), but could decrease the level of phosphorylated-Erk1/2 protein (P< 0.05). Conclusions: RNA interference of Ezrin could inhibit its expression in the pancreatic cancer cells line Panc-1, leading to a potent suppression of malignant behavior in vitro. Assessment of potential as a target for pancreatic cancer treatment is clearly warranted.

• Journal of Digestive Cancer Research
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• v.2 no.1
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• pp.28-31
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• 2014

Pancreatic cancer is a highly aggressive cancer with poor prognosis. Although, gemcitabine is the current standard regimen as first-line chemotherapy for advanced pancreatic cancer, effective regimens of second-line chemotherapy after gemcitabine failure have not been established yet. We report a case of gemcitabine refractory pancreatic cancer treated with second-line chemotherapy with FOLFIRINOX regimen. A 57-year-old-woman visited our hospital for pancreatic body mass detected by computed tomography (CT). The patient underwent distal pancreatectomy and splenectomy and the pathologic results after surgery demonstrated adenocarcinoma. Follow-up was performed after surgery and CT and positron emission tomography (PET) 4 months after surgery revealed multiple hepatic metastases. The patient underwent first-line chemotherapy with gemcitabine and erlotinib for recurred pancreatic cancer. However, CT after 7 cycles of the chemotherapy showed the progression of multiple hepatic metastases and switch to second-line chemotherapy with FOLFIRINOX was initiated. CT after 16 cycles of the FOLFIRINOX showed the complete remission of multiple hepatic metastases. The patient was admitted for infective endocarditis with septic pneumonia 17 months after the initiation of FOLFIRINOX. However, the patients died from the progression of septic embolism and acute respiratory distress syndrome.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.3
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• pp.229-234
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• 2022

When planning pancreaticoduodenectomy for pancreatic head cancer, the prevalence of anatomical variation of the proximal jejunal vein (PJV), the associated short-term surgical outcomes, and the level of PJV convergence to the superior mesenteric vein must be carefully analyzed from both technical and oncological points of view. The prevalence of the first jejunal trunk (FJT) and PJV located ventral to the superior mesenteric artery is 58%-88% and 13%-37%, respectively. Patients with the FJT had a larger amount of intraoperative bleeding and a higher proportion of patients requiring transfusions compared to those without a common trunk. The risk of transfusion was higher in patients with ventral PJV compared to those with dorsal PJV. Although less frequent, sacrificing the FJT can result in fatal venous congestion of the jejunum. Therefore, a well-planned approach for pancreaticoduodenectomy, based on preoperative evaluation of anatomical variation in the PJV, may help reduce intraoperative bleeding and postoperative morbidity. Additionally, the importance of invasion into the PJVs should be revisited in terms of resectability and oncological clearance.

• YAKHAK HOEJI
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• v.49 no.4
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• pp.335-339
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• 2005

In this study we investigated the effect of 3-methoxy-6-allylthiopyridazine on cell growth in BxPC3 and PANC1 human pancreatic cancer cells. The treatment with 3-methoxy-6-allylthiopyridazine for 48h decreased cell viability and induced apoptotic cell death in a dose-dependent manner, assessed by using the MTT assay and the flow cytometry, respectively. These results suggest that 3-methoxy-6-allylthiopyridazine may be a good candidate for the therapeutic management of human pancreatic cancers.

• Clinical Endoscopy
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• v.57 no.5
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• pp.675-682
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• 2024

Background/Aims: Pancreatic cancer poses significant challenges due to its tendency for late-stage diagnosis and high mortality rates. Cryoablation, a technique used to treat various types of cancer, has shown potential in enhancing the prognosis of pancreatic cancer when combined with other therapies. However, its implementation is often limited by the need for lengthy procedures and specialized equipment. This study aims to develop a cryoablation needle optimized for endoscopic ultrasonography to simplify its application in treating pancreatic cancer. Methods: The study involved conducting cryoablation experiments on swine liver tissue. It utilized cryo-needles to evaluate the extent of cell death across various temperatures and durations of cryoablation. Results: The cryoablation system, which employed liquid carbon dioxide, achieved rapid cooling, reaching temperatures below -60 ℃ within 30 seconds and maintained the cryoablation process for 200 seconds. These conditions resulted in necrosis of the liver tissue. Notable cellular changes were observed up to 15 mm away from the cryoablation needle. Conclusions: This experimental study successfully demonstrated the efficacy of using a cryo-needle for cryoablation in swine liver tissue. Further trials involving pancreatic tissue are expected to verify its effectiveness, underscoring the importance of continued research to establish its role as a complementary therapy in pancreatic cancer treatment.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.1
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• pp.113-117
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• 2022

Gallbladder cancer has a poor prognosis, especially in peritoneal carcinomatosis related to perforation of the gallbladder followed by bile spillage. Previously, curative-intent treatment was not considered in carcinomatosis from cancer of the biliary tract. A 72-year-old male was referred to the hospital with a perforated gallbladder cancer. Intraoperatively, the tumor was confined to the gallbladder and liver. We presented a case of intention-to-curative resection of perforated gallbladder cancer followed by intraoperative hyperthermic intraperitoneal chemotherapy.

• Clinical Endoscopy
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• v.56 no.2
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• pp.221-228
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• 2023

Background/Aims: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is essential for the diagnosis of pancreatic cancer. The feasibility of comprehensive genomic profiling (CGP) using samples obtained by EUS-TA has been under recent discussion. This study aimed to evaluate the utility of EUS-TA for CGP in a clinical setting. Methods: CGP was attempted in 178 samples obtained from 151 consecutive patients with pancreatic cancer at the Aichi Cancer Center between October 2019 and September 2021. We evaluated the adequacy of the samples for CGP and determined the factors associated with the adequacy of the samples obtained by EUS-TA retrospectively. Results: The overall adequacy for CGP was 65.2% (116/178), which was significantly different among the four sampling methods (EUS-TA vs. surgical specimen vs. percutaneous biopsy vs. duodenal biopsy, 56.0% [61/109] vs. 80.4% [41/51] vs. 76.5% [13/17] vs. 100.0% [1/1], respectively; p=0.022). In a univariate analysis, needle gauge/type was associated with adequacy (22 G fine-needle aspiration vs. 22 G fine-needle biopsy [FNB] vs. 19 G-FNB, 33.3% (5/15) vs. 53.5% (23/43) vs. 72.5% (29/40); p=0.022). The sample adequacy of 19 G-FNB for CGP was 72.5% (29/40), and there was no significant difference between 19 G-FNB and surgical specimens (p=0.375). Conclusions: To obtain adequate samples for CGP with EUS-TA, 19 G-FNB was shown to be the best in clinical practice. However, 19 G-FNB was not still sufficient, so further efforts are required to improve adequacy for CGP.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.274-283
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• 2022

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer. However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

• Natural Product Sciences
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• v.20 no.3
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• pp.170-175
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• 2014

Twenty five methanolic plant extracts were investigated to determine the anticancer activity against sonic hedgehog (shh)/Gli signaling pathway dependent cancer, PANC-1 human pancreatic cancer cells, through three screening programs. All extracts were inspected their inhibitory properties on sonic hedgehog-conditioned medium (shh-CM) induced alkaline phosphatase (ALP) activity in C3H10T1/2 mouse mesenchymal stem cells to examine whether the plant extracts affect the shh/Gli signaling pathway. Next, plant extracts were screened the ability to suppress the cell proliferation of PANC-1 human pancreatic cancer cells. Finally, active plant extracts from the two screening systems were evaluated for the suppressive effect on Gli-mediated transcriptional activity in PANC-1 cells. Among active plants, Cinnamomum cassia suppressed Gli-mediated transcriptional activity leading to the down-regulated expression of Gli-target genes such as Gli-1 and Patched-1 (Ptch-1). This study provides the consideration for the important role of natural products in drug discovery process as well as the basis for the further analysis of active plant and potential identification of novel bioactive compounds as inhibitors of Gli and therapeutic candidates against shh/Gli signaling pathway dependent cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2489-2493
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• 2015

Background: Loss of heterozygosity (LOH) on chromosomal regions is crucial in tumor progression and this study aimed to identify genome-wide LOH in pancreatic cancer. Materials and Methods: Single-nucleotide polymorphism (SNP) profiling data GSE32682 of human pancreatic samples snap-frozen during surgery were downloaded from Gene Expression Omnibus database. Genotype console software was used to perform data processing. Candidate genes with LOH were screened based on the genotype calls, SNP loci of LOH and dbSNP database. Gene annotation was performed to identify the functions of candidate genes using NCBI (the National Center for Biotechnology Information) database, followed by Gene Ontology, INTERPRO, PFAM and SMART annotation and UCSC Genome Browser track to the unannotated genes using DAVID (the Database for Annotation, Visualization and Integration Discovery). Results: The candidate genes with LOH identified in this study were MCU, MICU1 and OIT3 on chromosome 10. MCU was found to encode a calcium transporter and MICU1 could encode an essential regulator of mitochondrial $Ca^{2+}$ uptake. OIT3 possibly correlated with calcium binding revealed by the annotation analyses and was regulated by a large number of transcription factors including STAT, SOX9, CREB, NF-kB, PPARG and p53. Conclusions: Global genomic analysis of SNPs identified MICU1, MCU and OIT3 with LOH on chromosome 10, implying involvement of these genes in progression of pancreatic cancer.