• 한국간담췌외과학회지
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• 제26권1호
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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.

• Biomolecules & Therapeutics
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• 제30권3호
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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.

• Clinical Endoscopy
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• 제56권2호
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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.

• Natural Product Sciences
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• 제20권3호
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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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• 제16권6호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9667-9672
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• 2014

Background: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. Materials and Methods: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-${\alpha}$ (IFN-${\alpha}$) on the ligands of NK and T cells was assessed by flow cytometry. Results: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) may be a potential strategy for treating pancreatic adenocarcinoma.

• 대한암한의학회지
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• 제22권1호
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• pp.1-11
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• 2017

Objectives: The purpose of this study is to investigate preliminarily for development of the Korean medicine clinical practice guideline (CPG) for pancreatic cancer through the analysis of existing CPGs. Methods: Through searching the medical database such as Pubmed, SCOPUS, CNKI, Google Scholar, etc. The global CPGs within recent three years were collected and analyzed. In particular, recommendations related to the Korean medicine or Chinese medicine were made primarily in the Guidelines of Diagnosis and Therapy in Oncology with Traditional Chinese Medicine. Results: The six CPGs were mentioned in this study. The academic societies and organizations developing the CPGs were located in China, Japan, Europe and America. The contents of the CPGs were the clinical questions and statements, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy, palliative medicine, risk assessment, palliation and supportive care, follow-up and recurrence, Tumor-Node-Metastasis (TNM) staging. In the Guidelines of Diagnosis and Therapy in Oncology with Traditional Chinese Medicine, the etiology, mechanisms, herbal drugs, Chinese medicine assessment, complication, syndrome differentiation (SD), Chinese medicine treatment were described. Conclusions: In order to develop the proper Korean medicine CPG for pancreatic cancer and to adapt the correct integrative treatment program on the pancreatic cancer, institutional arrangements for cooperation with Korean medical communities and standardization of SD should be performed.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6001-6006
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• 2015

Background: Pancreatic cancer is the fourth leading cause of cancer related death with median survival ranging from 3 to 6 months for metastatic disease. Palliative chemotherapy has been the backbone of treatment in advanced stage and has evolved over time. Data pertaining to the disease are scarce from our part of the world where treatment poses a significant challenge due to lack of resources. Materials and Methods: A retrospective chart review was performed for all patients presenting with stage IV pancreatic carcinoma at a tertiary care hospital in Karachi, Pakistan between January 2008 and December 2012. Data were collected using a pre-designed, coded questionnaire looking at patient characteristics, treatment given and outcome. Results: 101 patients were found to be eligible. Mean age was $56.7{\pm}12.8years$, the male to female ratio was 2:1 and most patients had a good performance status. More than half of the tumors were located in the head (57%, n=58) and almost all were adenocarcinomas (95%, n=96). Some 58% (n=59) received first line chemotherapy of which 49% (n=29) received gemcitabine-based regimens and 39% (n=23) received FOLFIRINOX. The median progression free survival for gemcitabine based treatment was 2.9 months (IQR=1.6-5.6) as opposed to 7.3 months (IQR=4.5-9.2) for FOLFIRINOX (P=0.02). Median overall survival was 4.9 months (IQR=2.3-9.5) for first line gemcitabine based treatment and 10.5 months (IQR=7.0-13.2) for first line FOLFIRINOX therapy (P=0.002). Patients on FOLFIRINOX had better survival across all subgroups. Inpatient admissions and dose reductions were more frequent with FOLFIRINOX but the difference between the two regimens was not statistically significant. FOLFIRINOX could be successfully administered as outpatient therapy to a number of patients. Conclusions: FOLFIRINOX remains a suitable first line option in patients with metastatic pancreatic cancer with good performance status even in a resource-poor country where diagnostic and supportive care facilities may be less than optimal and cost is a limitation.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.753-759
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• 2012

Radixin, encoded by a gene on chromosome 11, plays important roles in cell motility, invasion and tumor progression. However, its function in pancreatic cancer remains elusive. In this study, radixin gene expression was suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method. We found that radixin shRNA caused down-regulation of radixin in PANC-1 cells, associated with inhibition of pancreatic cancer cell proliferation, survival, adhesion and invasive potential in vitro. When radixin-silenced cells were implanted in nude mice, tumor growth and microvessel density were significantly inhibited as compared to blank control cells or nonsense shRNA control cells. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin-silenced PANC-1 cells. Our results suggest that radixin might play a critical role in pancreatic cancer progression, possibly through invvolvement of down-regulation of TSP-1 and E-cadherin expression.

• Journal of Digestive Cancer Research
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• 제3권2호
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• pp.101-104
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• 2015

A 55-year-old man was admitted to the hospital for jaundice. Computed tomography (CT) scans showed a diffuse mass in the pancreas and peripancreatic area, with infiltration to of the whole pancreas, and overall reduced enhancement compared to normal pancreas. Esophagogastroduodenoscopy revealed elevated mucosal lesion covered hyperemic mucosa at duodenal bulb and ulcerative lesion at body of stomach. Endoscopic ultrasonography revealed an irregular mass with unclear boundaries was observed within the pancreas. Abrupt narrowing of mid to distal common bile duct was seen and the stricture was caused by compression of pancreatic mass. Plastic stent was inserted and clinical improvement was achieved including resolution of jaundice. The patient is currently being treated with combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. We report a case of primary pancreatic lymphoma presenting with obstructive jaundice.