• Title/Summary/Keyword: Pancreatic Cancer

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Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach

  • Buddham, Richa;Chauhan, Sweety;Narad, Priyanka;Mathur, Puniti
    • Journal of Microbiology and Biotechnology
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    • v.32 no.3
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    • pp.365-377
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    • 2022
  • Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

Glucocorticoid treatment independently affects expansion and transdifferentiation of porcine neonatal pancreas cell clusters

  • Kim, Ji-Won;Sun, Cheng-Lin;Jeon, Sung-Yoon;You, Young-Hye;Shin, Ju-Young;Lee, Seung-Hwan;Cho, Jae-Hyoung;Park, Chung-Gyu;Yoon, Kun-Ho
    • BMB Reports
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    • v.45 no.1
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    • pp.51-56
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    • 2012
  • The purpose of this study was to determine the effects of duration and timing of glucocorticoid treatment on the expansion and differentiation of porcine neonatal pancreas cell clusters (NPCCs) into ${\beta}$-cells. After transplantation of NPCCs, the ductal cyst area and ${\beta}$-cell mass in the grafts both showed positive and negative correlations with duration of dexamethasone (Dx) treatment. Pdx-1 and HNF-3${\beta}$ gene expression was significantly downregulated following Dx treatment, whereas PGC-1${\alpha}$ expression increased. Pancreatic duct cell apoptosis significantly increased following Dx treatment, whereas proliferation did not change. Altogether, transdifferentiation of porcine NPCCs into ${\beta}$-cells was influenced by the duration of Dx treatment, which might have been due to the suppression of key pancreatic transcription factors. PGC-1${\alpha}$ plays an important role in the expansion and transdifferentiation of porcine NPCCs, and the initial 2 weeks following transplantation of porcine NPCCs is a critical period in determining the final ${\beta}$-cell mass in grafts.

Hypermethylation-mediated silencing of NDRG4 promotes pancreatic ductal adenocarcinoma by regulating mitochondrial function

  • Shi, Hao-Hong;Liu, Hai-E;Luo, Xing-Jing
    • BMB Reports
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    • v.53 no.12
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    • pp.658-663
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    • 2020
  • The N-myc downstream regulated gene (NDRG) family members are dysregulated in several tumors. Functionally, NDRGs play an important role in the malignant progression of cancer cells. However, little is known about the potential implications of NDRG4 in pancreatic ductal adenocarcinoma (PDAC). The aim of the current study was to elucidate the expression pattern of NDRG4 in PDAC and evaluate its potential cellular biological effects. Here, we firstly report that epigenetic-mediated silencing of NDRG4 promotes PDAC by regulating mitochondrial function. Data mining demonstrated that NDRG4 was significantly down-regulated in PDAC tissues and cells. PDAC patients with low NDRG4 expression showed poor prognosis. Epigenetic regulation by DNA methylation was closely associated with NDRG4 down-regulation. NDRG4 overexpression dramatically suppressed PDAC cell growth and metastasis. Further functional analysis demonstrated that up-regulated NDRG4 in SW1990 and Canpan1 cells resulted in attenuated mitochondrial function, including reduced ATP production, decreased mitochondrial membrane potential, and increased fragmented mitochondria. However, opposite results were obtained for HPNE cells with NDRG4 knockdown. These results indicate that hypermethylation-driven silencing of NDRG4 can promote PDAC by regulating mitochondrial function and that NDRG4 could be as a potential biomarker for PDAC patients.

Automatic Pancreas Detection on Abdominal CT Images using Intensity Normalization and Faster R-CNN (복부 CT 영상에서 밝기값 정규화 및 Faster R-CNN을 이용한 자동 췌장 검출)

  • Choi, Si-Eun;Lee, Seong-Eun;Hong, Helen
    • Journal of Korea Multimedia Society
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    • v.24 no.3
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    • pp.396-405
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    • 2021
  • In surgery to remove pancreatic cancer, it is important to figure out the shape of a patient's pancreas. However, previous studies have a limit to detect a pancreas automatically in abdominal CT images, because the pancreas varies in shape, size and location by patient. Therefore, in this paper, we propose a method of learning various shapes of pancreas according to the patients and adjacent slices using Faster R-CNN based on Inception V2, and automatically detecting the pancreas from abdominal CT images. Model training and testing were performed using the NIH Pancreas-CT Dataset, and intensity normalization was applied to all data to improve pancreatic detection accuracy. Additionally, according to the shape of the pancreas, the test dataset was classified into top, middle, and bottom slices to evaluate the model's performance on each data. The results show that the top data's mAP@.50IoU achieved 91.7% and the bottom data's mAP@.50IoU achieved 95.4%, and the highest performance was the middle data's mAP@.50IoU, 98.5%. Thus, we have confirmed that the model can accurately detect the pancreas in CT images.

Relative Risk Ratio of Residents Living Near the Municipal Solid Waste Landfill Site at Some Province in South Korea

  • Lee Jin-Heon;Choi Jin-Ha
    • Journal of Environmental Health Sciences
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    • v.32 no.3
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    • pp.240-248
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    • 2006
  • The purposes of this study were to investigate the symptoms, diseases and deaths of residents living near the municipal solid waste landfill site, and to compare the relative risk ratio of their adverse health effects with control group. In self-evaluation, the scores were especially severe lowest in residents of v2 and v3 villages(which were located about 500 m toward under the landfill site) such as 32.2 and 16.7 for village-environment, 24.8 and 16.0 for management of landfill site, and 23.5 and 16.5 for confidence of environmental policy, respectively. On symptoms, relative risk ratios were also highest as 3.53 and 3.55 for breathing difficulty, and 3.36 and 3.00 for respiratory symptom in v2 and v3 villages, respectively. On morbidity, they were slightly high as much as 1.39 and 1.24 in v5 and v2 villages, respectively. On mortality, relative risk ratios were $1.15{\sim}2.46$ in experimental villages. They were especially high as much as 2.46 in v3 village where located near under the landfill site, and also 2.14 in v5 village where located at area affected with the landfill site, but near the sea. The rate of cancer causing death was average 35.2% of total deaths. It was very highest as much as 61.1 % in v2 village, where was closely located near under the landfill site. Cancers causing death in this village were lung cancer(3 cases), larynx cancer(2 cases), stomach cancer(2 cases), pancreatic cancer(1 case), thryoid cancer(1 case), leukemia(1 case) and other(1 case). Our data, although based on limited number of cases and geographical coverage, suggest that residents living near landfill site have the increasing relative risks of various symptoms and mortality causing cancer. No causal mechanisms are available to explain these findings. But the possibility of a causal association between the increased adverse health effects and the municipal solid waste landfill site cannot be fully excluded.

Expression and Clinical Significance of MicroRNA-376a in Colorectal Cancer

  • Mo, Zhan-Hao;Wu, Xiao-Dong;Li, Shuo;Fei, Bing-Yuan;Zhang, Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9523-9527
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    • 2014
  • The incidence of colorectal cancer (CRC) is increasing in many Asian countries and microRNAs have already been proven to be associated with tumorigenesis. Currently, microRNA-376a (miR-376a) expression and association with clinical factors in CRC remains unclear. In this study, real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was carried out on 53 matched pairs of CRC and adjacent normal mucosa to investigate the expression levels of miR-376a. According to the high or low expression of miR-376a, patients were divided into two groups. The relationship between miR-376a expression and clinicopathological factors of 53 patients was evaluated. Survival analysis of 53 CRC patients was performed with clinical follow-up information and survival curves were assessed by the Kaplan-Meier method. Immunohistochemistry (IHC) staining was performed on sections of paraffin-embedded tissue to investigate the vascular endothelial growth factor (VEGF) expression. MiR-376a showed low expression in cancer tissues compared to the adjacent normal tissues and altered high miR-376a expression tended to be positively correlated with advanced lymph node metastasis and shorter patient survival. VEGF IHC positivity was significantly more common in patients with high expression levels of miR-376a.Those results demonstrated that miR-376a may be a meaningful prognostic biomarker and potential therapeutic target in colorectal cancer.

Comparison of Clinical Characteristics between Occupational and Sporadic Young-Onset Cholangiocarcinoma

  • Kaneko, Rena;Kubo, Shoji;Sato, Yuzuru
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.7195-7200
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    • 2015
  • Background: Since seventeen employees of an offset printing company in Osaka, Japan developed cholangiocarcinoma it has become recognized as an occupational cancer. This study investigated the differences of clinical features between occupational cholangiocarcinoma and sporadic young-onset cholangiocarcinoma. Materials and Methods: Thirty-four young adults (<50 years old) with sporadic cholangiocarcinoma were extracted from the Rosai Hospital Group database (sporadic group) and their clinical features were compared with those of 17 patients with occupational cholangiocarcinoma (occupational group). Results: The 34 patients in the sporadic group were treated for cholangiocarcinoma at 16 different Rosai hospitals. There were significant differences of age (p<0.01), gender (p<0.01), abnormal laboratory tests (p<0.01), and tumor location (p<0.01) between the two groups. The percentage of patients with abnormal laboratory tests was significantly higher in the occupational group than in the sporadic group (p<0.001). Regional dilation of bile ducts, which is a characteristic of occupational cholangiocarcinoma, was not observed in the sporadic group. Conclusions: No cluster of cholangiocarcinoma cases was identified in the Rosai Hospital database. There were differences of clinical features between occupational and sporadic cholangiocarcinoma, which might be helpful for diagnosing occupational cholangiocarcinoma in the future.

Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches

  • Bano, Nusrat;Najam, Rahila;Qazi, Faaiza;Mateen, Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1637-1641
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    • 2016
  • Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.

A Clinical Survey of Patients of Pain Clinic (통증치료실 환자의 임상통계적 고찰)

  • Jang, Young-Ho;Lee, Jung-Koo;Cheun, Jae-Kyu;Chung, Jung-Kil
    • The Korean Journal of Pain
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    • v.8 no.1
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    • pp.103-109
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    • 1995
  • The pain clinic in our institution opened on of June, 1984. since then until December 1994, we have had 1,741 patients who had been treated on an out-patient basis. The patients were analysed retrospectively according to their sex, age, and retrospective disease. There were 969 male(55.7%) and 772 female patients(44.3%) In the age distribution of the patients, the highest incidence was in the forties with 463 patients(26.6%). The second highest age incidence was in the thirties with 357 patients(20.5%), and the third highest age incidence was in the sixties with 341 patients(19.6%). In this figure, there were 203(26.6%) stomach cancer patients, 135(17.7%) cervix and uterine cencer patients, 81(10.6%) colorectal cancer patients, 74(9.7%) hepatoma patients, and 68 (8.9%) pancreatic cancer patients. The patients with non malignant chronic pain numbered 977(56.1%). In this figure, there were low back pain of 188(19.2%), sudden deafness of 17.5%, Buerger's disease of 63(6.5%) and postherpetic neuralgia of 56(5.7%).

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Discovery to Human Disease Research: Proteo-Metabolomics Analysis

  • Minjoong Joo;Jeong-Hun Mok;Van-An Duong;Jong-Moon Park;Hookeun Lee
    • Mass Spectrometry Letters
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    • v.15 no.2
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    • pp.69 -78
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    • 2024
  • The advancement of high-throughput omics technologies and systems biology is essential for understanding complex biological mechanisms and diseases. The integration of proteomics and metabolomics provides comprehensive insights into cellular functions and disease pathology, driven by developments in mass spectrometry (MS) technologies, including electrospray ionization (ESI). These advancements are crucial for interpreting biological systems effectively. However, integrating these technologies poses challenges. Compared to genomic, proteomics and metabolomics have limitations in throughput, and data integration. This review examines developments in MS equipped electrospray ionization (ESI), and their importance in the effective interpretation of biological mechanisms. The review also discusses developments in sample preparation, such as Simultaneous Metabolite, Protein, Lipid Extraction (SIMPLEX), analytical techniques, and data analysis, highlighting the application of these technologies in the study of cancer or Huntington's disease, underscoring the potential for personalized medicine and diagnostic accuracy. Efforts by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and integrative data analysis methods such as O2PLS and OnPLS extract statistical similarities between metabolomic and proteomic data. System modeling techniques that mathematically explain and predict system responses are also covered. This practical application also shows significant improvements in cancer research, diagnostic accuracy and therapeutic targeting for diseases like pancreatic ductal adenocarcinoma, non-small cell lung cancer, and Huntington's disease. These approaches enable researchers to develop standardized protocols, and interoperable software and databases, expanding multi-omics research application in clinical practice.