scholarly journals The Role of PPAR-γand Its Interaction with COX-2 in Pancreatic Cancer

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Guido Eibl
Keyword(s):  
Pancreatic Cancer ◽  
Human Cancer ◽  
Biological Significance ◽  
Peroxisome Proliferators ◽  
Antiproliferative Effects ◽  
Biologically Relevant ◽  
Pancreatic Cancers ◽  
Current Review ◽  
Cox 2

In recent years, the study of the peroxisome proliferators activated receptor gamma (PPAR-γ) as a potential target for cancer prevention and therapy has gained a strong interest. However, the overall biological significance of PPAR-γin cancer development and progression is still controversial. While many reports documented antiproliferative effects in human cancer cell and animal models, several studies demonstrating potential tumor promoting actions of PPAR-γligands raised considerable concerns about the role of PPAR-γin human cancers. Controversy also exists about the role of PPAR-γin human pancreatic cancers. The current review summarizes the data about PPAR-γin pancreatic cancer and highlights the biologically relevant interactions between the cyclooxygenase and PPAR system.

Telomerase: A Potential Diagnostic and Therapeutic Tool in Canine Oncology

2003 ◽  
Vol 40 (1) ◽  
pp. 1-7 ◽  
Author(s):  
D. J. Argyle ◽  
L. Nasir
Keyword(s):  
Human Cancer ◽  
Biological Significance ◽  
Telomerase Activity ◽  
Clinical Implications ◽  
Therapeutic Tool ◽  
Vast Number ◽  
Somatic Tissues ◽  
Canine Tumors ◽  
Cancer Tissues

In recent years there has been considerable interest in telomerase as a target for therapeutic intervention in oncology. This largely stems from the vast number of studies that have demonstrated expression and activity of the enzyme telomerase in the majority of human cancer tissues with little or no activity detectable in normal somatic tissues. These studies have led to an interest in the role of telomerase in cancers associated with domesticated species, in particular tumors that affect dogs. This article reviews the biology of telomerase and the biological significance of telomerase activity in canine tumors and discusses the clinical implications of telomerase expression in canine cancers with regard to therapeutics and diagnostics.

Silencing of Astrocyte elevated gene-1 (AEG-1) inhibits proliferation, migration, and invasiveness, and promotes apoptosis in pancreatic cancer cells

2019 ◽  
Vol 97 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Xing Yang ◽  
Shaowei Song
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Hairpin Rna ◽  
Knock Down ◽  
Pancreatic Cancers ◽  
Pancreatic Cancer Cells ◽  
Apoptosis Assay ◽  
Matrix Metallopeptidase ◽  
Coated Membrane

To investigate the role of Astrocyte elevated gene-1 (AEG-1) in the development and progress of pancreatic cancer, short hairpin RNA (shRNA) was inserted into the RNA interference vector to knock-down the endogenous AEG-1 in two pancreatic cancer cell lines: AsPC-1 and PANC-1. Our results showed that silencing of AEG-1 suppressed the proliferation, colony formation ability, and cell stemness of AsPC-1 and PANC-1 cells, and inhibited their G1-to-S phase transition. Results from apoptosis assay showed that knock-down of AEG-1 led to cell apoptosis. The expression of anti-apoptotic Bcl-2 was downregulated and that of the pro-apoptotic Bax and cleaved caspase-3 was upregulated in AEG-1-silenced pancreatic cancer cells. Further, the capability of AEG-1-silenced cells to migrate and to invade through the Matrigel-coated membrane was weaker, and the expression of matrix metallopeptidase 2 (MMP-2) and MMP-9 were decreased. Moreover, the AKT–β-catenin signaling pathway was inhibited in the cells with knock-down of AEG-1. In addition, the growth of xenograft tumors formed by AsPC-1 and PANC-1 cells was suppressed by AEG-1 shRNA. In conclusion, our study demonstrates that pancreatic cancer cells require AEG-1 to maintain their survival and metastasis, suggesting AEG-1 as a potential target for the treatment of pancreatic cancers.

scholarly journals Endoscopic ultrasound (EUS) and the management of pancreatic cancer

2020 ◽  
Vol 7 (1) ◽  
pp. e000408
Author(s):  
Muhammad Nadeem Yousaf ◽  
Fizah S Chaudhary ◽  
Amrat Ehsan ◽  
Alejandro L Suarez ◽  
Thiruvengadam Muniraj ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Endoscopic Ultrasound ◽  
Medical Oncology ◽  
Surgical Oncology ◽  
Ductal Adenocarcinoma ◽  
Radiological Imaging ◽  
Endoscopic Retrograde ◽  
Pancreatic Cancers ◽  
Related Mortality

Pancreatic cancer is one of the leading causes of cancer-related mortality in western countries. Early diagnosis of pancreatic cancers plays a key role in the management by identification of patients who are surgical candidates. The advancement in the radiological imaging and interventional endoscopy (including endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography and endoscopic enteral stenting techniques) has a significant impact in the diagnostic evaluation, staging and treatment of pancreatic cancer. The multidisciplinary involvement of radiology, gastroenterology, medical oncology and surgical oncology is central to the management of patients with pancreatic cancers. This review aims to highlight the diagnostic and therapeutic role of EUS in the management of patients with pancreatic malignancy, especially pancreatic ductal adenocarcinoma.

scholarly journals Overexpressed WDR3 Induces the Activation of Hippo Pathway by Interacting with GATA4 in Pancreatic Cancer

2020 ◽  
Author(s):  
Wenjie Su ◽  
Shikai Zhu ◽  
Kai Chen ◽  
Hongji Yang ◽  
Mingwu Tian ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Human Cancer ◽  
Critical Role ◽  
Biological Role ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Pancreatic Cancer Cells ◽  
Independent Functions

Abstract Background: WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer.Methods: The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions.Results: Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, in pancreatic cancer cells.Conclusions: We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through an interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.

scholarly journals DOG1 is commonly expressed in pancreatic adenocarcinoma but unrelated to cancer aggressiveness

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11905
Author(s):  
Kristina Jansen ◽  
Franziska Büscheck ◽  
Katharina Moeller ◽  
Martina Kluth ◽  
Claudia Hube-Magg ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Stage ◽  
Tissue Sections ◽  
Pancreatic Cancers ◽  
Repair Protein ◽  
Potential Biomarker ◽  
Cancer Aggressiveness ◽  
Weak Expression ◽  
Ampulla Vateri

Background DOG1 (ANO1; TMEM16A) is a voltage-gated calcium-activated chloride and bicarbonate channel. DOG1 is physiologically expressed in Cajal cells, where it plays an important role in regulating intestinal motility and its expression is a diagnostic hallmark of gastrointestinal stromal tumors (GIST). Data on a possible role of DOG1 in pancreatic cancer are rare and controversial. The aim of our study was to clarify the prevalence of DOG1 expression in pancreatic cancer and to study its association with parameters of cancer aggressiveness. Methods DOG1 expression was analyzed by immunohistochemistry in 599 pancreatic cancers in a tissue microarray format and in 12 cases of pancreatitis on large tissue sections. Results DOG1 expression was always absent in normal pancreas but a focal weak expression was seen in four of 12 cases of pancreatitis. DOG1 expression was, however, common in pancreatic cancer. Membranous and cytoplasmic DOG1 expression in tumor cells was highest in pancreatic ductal adenocarcinomas (61% of 444 interpretable cases), followed by cancers of the ampulla Vateri (43% of 51 interpretable cases), and absent in 6 acinus cell carcinomas. DOG1 expression in tumor associated stroma cells was seen in 76 of 444 (17%) pancreatic ductal adenocarcinomas and in seven of 51 (14%) cancers of the ampulla Vateri. Both tumoral and stromal DOG1 expression were unrelated to tumor stage, grade, lymph node and distant metastasis, mismatch repair protein deficiency and the density of CD8 positive cytotoxic T-lymphocytes in the subgroups of ductal adenocarcinomas and cancers of ampulla Vateri. Overall, the results of our study indicate that DOG1 may represent a potential biomarker for pancreatic cancer diagnosis and a putative therapeutic target in pancreatic cancer. However, DOG1 expression is unrelated to pancreatic cancer aggressiveness.

scholarly journals Pancreatic Cancer Imaging: What the Surgeon Wants to Know?

2020 ◽  
Vol 3 (01) ◽  
pp. 040-052
Author(s):  
Ajaykumar C. Morani ◽  
Ahmed Taher ◽  
Nisha S. Ramani ◽  
Corey T. Jensen ◽  
Asif Patel ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Imaging Modality ◽  
Accurate Determination ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Pancreatic Tumors ◽  
Vascular Involvement ◽  
Surgical Removal ◽  
Pancreatic Cancers

AbstractPancreatic cancer is rare but is one of the deadliest cancers. Complete surgical removal of the cancer with negative margins is the only potentially curative treatment. However, majority of the cases present with distant metastases and/or locally advanced disease, and only a limited subset (up to 20%) of patients are surgical candidates. Therefore, accurate staging of pancreatic cancer is very important for treatment planning. It is very important to distinguish between patients who are surgical candidates and those who would need palliative treatment. Imaging plays a crucial role in the detection of the primary tumor, vascular involvement and variants, metastasis, prediction of resectability, and monitoring treatment response. High-resolution multidetector computed tomography (CT) is the primary imaging modality of choice for diagnosing and staging pancreatic cancers. Nevertheless, integration of ultrasound, CT, and magnetic resonance imaging (MRI) may be needed for accurate determination of the tumor extent and optimal management. Herein, we aim to provide a radiological review for “what the surgeon wants to know about pancreatic cancer?” In this review, we highlight the main types of invasive pancreatic cancers and discuss the role of imaging in determining the resectability of pancreatic tumors and the role of neoadjuvant treatment in downstaging borderline or unresectable cases in addition to featuring significant postsurgical complications.

Actionable targets in pancreatic cancer detected by immunohistochemistry (IHC), microarray (MA) fluorescent in situ hybridization (FISH), and mutational analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4013-4013 ◽  
Author(s):  
Daniel D. Von Hoff ◽  
Ramesh K. Ramanathan ◽  
Douglas B. Evans ◽  
Michael J. Demeure ◽  
Todd Maney ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mutational Analysis ◽  
Gene Copy ◽  
Study Cohort ◽  
Kras Mutations ◽  
New Therapeutic Approaches ◽  
Pancreatic Cancers ◽  
Genome Expression ◽  
Cox 2 ◽  
Whole Genome Expression

4013 Background: A great need exists for new therapeutic approaches for patients with pancreatic cancer. Methods: The study cohort included 1029 patients analyzedfor a.) up to 29 different immunohistochemical biomarkers – (e.g., COX-2, MGMT, PGP, RRM1, TOPOI, TOPOII, SPARC etc.)b.); in up to 450 patients’ specimens a whole genome expression analysis was performed using HumanHT-12 v4 beadChips ( Illumina Inc.,San Diego, CA) c.) in up to 695 patients FISH for c-Myc, EGFR, HER2 and TOPO2A gene copy amplifications; and d.) in up to 783 patients sequencing for KRAS, EGFR, PI3CA and BRAF, was performed. Results: IHC identified actionable targets included; 74% high COX-2; 57% negative ERCC1; 8% negative MGMT; 22% negative MRP1; 47% negative PGP; 77% low RRM1, 44% high SPARC; 30% high TOPO2A; 61% high TOPOI and 73% negative TS. Other biologically important findings by IHC for possible new therapeutics included 27% negative PTEN; and 20% high PDGFR. Microarray results presented multiple overexpressed targets for consideration including 36% of specimens with overexpressed adenosine deaminase; 28% asparagine synthase; 17% BCL2; 20% survivin; 23% carboxylesterase; 67% DNMT1; 40% thymidine phosphatase; 49% EPHA2 (and others in the src family of kinases); 57% FOLR2; 41% HDAC1; 62% HiF1α; 23% IL2RA (CD25); 46% NFkB1; 48% OGFR; 32% RARA; 26% VEGFR; and 43% vitamin D receptor. FISH yielded 2% amplified EGFR and 10% amplified Her2neu. Sequencing noted 73% mutated KRAS and 3% mutated PIK3CA. Conclusions: Examining actionable targets in patients’ pancreatic cancers (a)reiterates the commonality and importance of KRAS mutations in this disease (needs renewed targeting effort) (b)suggests that TOPO2 inhibitors (particularly if transport into tumor can be improved) should be examined in this disease (c)suggests other pathways to target including DNA repair, epigenetic, Src and inflammation (d) suggests protein turnover, amino acid targets and folate receptor2 as fresh areas to explore against the disease. Supported in part by a Stand Up To Cancer Dream Team Award.

scholarly journals Cell Intrinsic Role of COX-2 in Pancreatic Cancer Development

2012 ◽  
Vol 11 (10) ◽  
pp. 2127-2137 ◽  
Author(s):  
Reginald Hill ◽  
Yunfeng Li ◽  
Linh M. Tran ◽  
Sarah Dry ◽  
Joseph Hargan Calvopina ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Development ◽  
Cox 2
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