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 Long noncoding RNA 00976 promotes pancreatic cancer progression through OTUD7B by sponging miR-137 involving EGFR/MAPK pathway

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Shan Lei ◽  
Zhiwei He ◽  
Tengxiang Chen ◽  
Xingjun Guo ◽  
Zhirui Zeng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Migration And Invasion ◽  
Potential Biomarker

Abstract Background Accumulation evidence indicates the vital role of long non-coding RNAs (lncRNAs) in tumorigenesis and the progression of malignant tumors, including pancreatic cancer (PC). However, the role and the molecular mechanism of long non-coding RNA 00976 is unclear in pancreatic cancer. Methods In situ hybridization (ISH) and qRT-PCR was performed to investigate the association between linc00976 expression and the clinicopathological characteristics and prognosis of patients with PC. Subsequently, linc00976 over-expression vector and shRNAs were transfected into PC cells to up-regulate or down-regulate linc00976 expression. Loss- and gain-of function assays were performed to investigate the role of linc00976 in proliferation and metastasis in vitro and vivo. ITRAQ, bioinformatic analysis and rescue assay were used to illustrate the ceRNA mechanism network of linc00976/miR-137/OTUD7B and its downstream EGFR/MAPK signaling pathway. Results linc00976 expression was overexpressed in PC tissues and cell lines and was positively associated with poorer survival in patients with PC. Function studies revealed that linc00976 knockdown significantly suppressed cell proliferation, migration and invasion in vivo and in vitro, whereas its overexpression reversed these effects. Based on Itraq results and online database prediction, Ovarian tumor proteases OTUD7B was found as a downstream gene of linc00976, which deubiquitinated EGFR mediates MAPK signaling activation. Furthermore, Bioinformatics analysis and luciferase assays and rescue experiments revealed that linc00976/miR137/OTUD7B established the ceRNA network modulating PC cell proliferation and tumor growth. Conclusion The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137. Ultimately, OTUD7B mediates EGFR and MAPK signaling pathway, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a potential biomarker and therapeutic target for PC.

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 Immune-Based Therapies and the Role of Microsatellite Instability in Pancreatic Cancer

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 33
Author(s):  
Michele Ghidini ◽  
Andrea Lampis ◽  
Milko B. Mirchev ◽  
Ali Fuat Okuducu ◽  
Margherita Ratti ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Microsatellite Instability ◽  
Cancer Patients ◽  
Current Knowledge ◽  
Treatment Options ◽  
Survival Rates ◽  
High Morbidity ◽  
Pancreatic Cancers ◽  
Repair Protein ◽  
Protein Functions

Pancreatic cancer is one of the most aggressive malignancies with limited treatment options thus resulting in high morbidity and mortality. Among all cancers, with a five-year survival rates of only 2–9%, pancreatic cancer holds the worst prognostic outcome for patients. To improve the overall survival, an earlier diagnosis and stratification of cancer patients for personalized treatment options are urgent needs. A minority of pancreatic cancers belong to the spectrum of Lynch syndrome-associated cancers and are characterized by microsatellite instability (MSI). MSI is a consequence of defective mismatch repair protein functions and it has been well characterized in other gastrointestinal tumors such as colorectal and gastric cancer. In the latter, high levels of MSI are linked to a better prognosis and to an increased benefit to immune-based therapies. Therefore, the same therapies could offer an opportunity of treatment for pancreatic cancer patients with MSI. In this review, we summarize the current knowledge about immune-based therapies and MSI in pancreatic cancer.

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.

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.

scholarly journals Molecular Functions of Hydrogen Sulfide in Cancer

2021 ◽  
Vol 28 (3) ◽  
pp. 437-456
Author(s):  
Rodney E. Shackelford ◽  
Islam Z. Mohammad ◽  
Andrew T. Meram ◽  
David Kim ◽  
Fawaz Alotaibi ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Molecular Mechanisms ◽  
Chemotherapy Resistance ◽  
Tumor Stage ◽  
Enzyme Expression ◽  
Mesenchymal Transition ◽  
Repair Protein ◽  
Dna Repair Protein ◽  
Worse Prognosis

Hydrogen sulfide (H2S) is a gasotransmitter that exerts a multitude of functions in both physiologic and pathophysiologic processes. H2S-synthesizing enzymes are increased in a variety of human malignancies, including colon, prostate, breast, renal, urothelial, ovarian, oral squamous cell, and thyroid cancers. In cancer, H2S promotes tumor growth, cellular and mitochondrial bioenergetics, migration, invasion, angiogenesis, tumor blood flow, metastasis, epithelia–mesenchymal transition, DNA repair, protein sulfhydration, and chemotherapy resistance Additionally, in some malignancies, increased H2S-synthesizing enzyme expression correlates with a worse prognosis and a higher tumor stage. Here we review the role of H2S in cancer, with an emphasis on the molecular mechanisms by which H2S promotes cancer development, progression, dedifferentiation, and metastasis.

The miR-21 potential of serving as a biomarker for liver diseases in clinical practice

2020 ◽  
Vol 48 (5) ◽  
pp. 2295-2305
Author(s):  
Jiawei Zhang ◽  
Dandan Li ◽  
Rui Zhang ◽  
Peng Gao ◽  
Rongxue Peng ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Liver Diseases ◽  
Hepatic Disease ◽  
Noninvasive Detection ◽  
Diagnosis And Prognosis ◽  
Expected Performance ◽  
Potential Biomarker ◽  
Disease Condition ◽  
Complex Regulatory Network

The role of miR-21 in the pathogenesis of various liver diseases, together with the possibility of detecting microRNA in the circulation, makes miR-21 a potential biomarker for noninvasive detection. In this review, we summarize the potential utility of extracellular miR-21 in the clinical management of hepatic disease patients and compared it with the current clinical practice. MiR-21 shows screening and prognostic value for liver cancer. In liver cirrhosis, miR-21 may serve as a biomarker for the differentiating diagnosis and prognosis. MiR-21 is also a potential biomarker for the severity of hepatitis. We elucidate the disease condition under which miR-21 testing can reach the expected performance. Though miR-21 is a key regulator of liver diseases, microRNAs coordinate with each other in the complex regulatory network. As a result, the performance of miR-21 is better when combined with other microRNAs or classical biomarkers under certain clinical circumstances.

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