Signal transducer and activator of transcription 3β in pancreatic cancer

2010 ◽  
Vol 5 (4) ◽  
pp. 435-438
Author(s):  
Agnieszka Dettlaff-Pokora ◽  
Justyna Kostro

AbstractSignal transducer and activator of transcription 3 (STAT3) has four isoforms: α, β, γ and δ. STAT3α and STAT3β are the transcriptionally active isoforms, while STAT3γ and STAT3δ are the products of STAT3 proteolytic degradation. STAT3 plays an important role in angiogenesis, cell proliferation and apoptosis. High levels of STAT3β in blood cells from acute leukaemia patients have been reported, suggesting that STAT3β may play an important role in cancerogenesis. Fourteen pancreatic cancer patients and six chronic pancreatitis patients were included in this pilot study. Levels of STAT3 isoforms from samples with pancreatic cancer and in adjacent histologically-normal pancreatic tissue were analysed. Pancreas from chronic pancreatitis patients served as a non-neoplastic tissue. Western-blot analysis of STAT3 proteins with the use of anti-STAT3 antibodies was performed. STAT3α and STAT3β isoforms in both cancerous and in adjacent normal tissues were found in 10 of 14. In chronic pancreatitis patients, only STAT3α and STAT3δ were detected. STAT3β was absent in pancreas from chronic pancreatitis patients, in contrast to pancreatic cancer patients. The presence of STAT3β in pancreatic cancer and in adjacent histologically-normal tissues, but not in inflamed tissues suggests that STAT3β may play a key role in cancer development.

2020 ◽  
Author(s):  
Chao Zhang ◽  
Wenhao Tang ◽  
Yanyuan Tu ◽  
Zurong Yuan ◽  
Wei Wang ◽  
...  

Abstract Background:Pancreatic cancer is difficult to cure and many factors influence patient prognosis, of which autophagy is a recent research hotspot, and GABARAP plays a key role in autophagy, which has been found to interfere with cancer cell survival and metastasis in a variety of tumours. In this study, we analysed the correlation between GABARAP and patient prognosis in pancreatic cancer, as well as its correlation with clinicopathological parameters and its impact on the efficacy of chemotherapy in pancreatic cancer patients.Methods: The pancreatic tissues of 76 pancreatic cancer patients after R0 resection were screened according to the criteria, and the expression levels of GABARAP were determined by using immunohistochemistry (MaxVision) to label the pancreatic cancer tissues and normal pancreatic tissue around carcinoma in these two types of specimens, and the relationship between GABARAP and other factors and the disease-free and overall survival of patients after radical pancreatic cancer treatment was evaluated by single factor survival analysis and Cox regression analysis.Results:The expression ratio of GABARAP in pancreatic cancer tissue was drastically higher than that in normal pancreatic tissue adjacent to cancer. Cox regression model evaluation showed that GABARAP and postoperative adjuvant chemotherapy were the overall survival of patients after radical pancreatic cancer Period independent prognostic indicators and both are protective factors for the prognosis of pancreatic cancer patients. Further data analysis found that postoperative chemotherapy drastically increased the total patient Survival period in GABARAP-negative patients but had no drastically effect on the patient's relapse-free survival period.Conclusion: The expression of GABARAP in pancreatic cancer tissues was drastically up-regulated, and patients with high expression of GABARAP in pancreatic cancer tissues had better prognosis, but had no drastically effect on the relapse-free survival of patients after radical operation of pancreatic cancer. The expression of GABARAP in pancreatic cancer tissues and Postoperative adjuvant chemotherapy is an independent indicator of patients' prognosis after radical pancreatic cancer resection. Both are protective factors. The high expression of GABARAP in pancreatic cancer may indicate that the adjuvant chemotherapy is low benefit.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Michael Hocke ◽  
Christoph F. Dietrich

Discriminating between focal chronic pancreatitis and pancreatic cancer is always a challenge in clinical medicine. Contrast-enhanced endoscopic ultrasound using Doppler techniques can uniquely reveal different vascularisation patterns in pancreatic tissue alterated by chronic inflammatory processes and even allows a discrimination from pancreatic cancer. This paper will describe the basics of contrast-enhanced high mechanical index endoscopic ultrasound (CEHMI EUS) and contrast enhanced low mechanical index endoscopic ultrasound (CELMI EUS) and explain the pathophysiological differences of the vascularisation of chronic pancreatitis and pancreatic carcinoma. Furthermore it will discuss how to use these techniques in daily clinical practice.


2001 ◽  
Vol 125 (6) ◽  
pp. 765-769
Author(s):  
Jin Zhao ◽  
Sharon X. Liang ◽  
Lou Savas ◽  
Barbara F. Banner

Abstract Background.—The diagnosis of malignancy in pancreatic mucinous cystic tumors depends on demonstrating invasion that may be focal and require extensive sectioning. Objective.—To explore markers that may indicate malignant potential in mucinous cystic tumors. Design.—Routinely processed sections from resected specimens of 12 normal pancreata, 14 pancreata with chronic pancreatitis, 9 mucinous cystic tumors, and 30 invasive adenocarcinomas were immunostained with antibodies to p53, HER-2/neu, epithelial growth factor receptor (EGFR), transforming growth factor α (TGF-α), and Ki-67. Results.—Expression of p53, HER-2/neu, and Ki-67 was significantly more frequent in mucinous tumors than in normal pancreatic tissue and chronic pancreatitis tissue (P = .0003 to .05). Strong expression (more than one third of cells positive) and strong intensity (2+ and 3+) of staining of p53 and EGFR were seen only in carcinomas. Coexpression of p53/HER-2/neu and EGFR/HER-2/neu and a frequency of Ki-67+ nuclei of greater than 5% of cells discriminated between mucinous tumors and normal pancreatic tissue and chronic pancreatitis tissue. p53 expression was significantly more frequent in carcinomas than in mucinous tumor (P = .0326). Coexpression of p53/EGFR discriminated between mucinous tumors and carcinomas; however, TGF-α was not discriminative. Conclusions.—The immunostaining panel of p53, HER-2/neu, Ki-67, and EGFR can be helpful in indicating malignant potential in mucinous tumors of pancreas in routine pathology practice.


2013 ◽  
Vol 12 (1) ◽  
pp. 104 ◽  
Author(s):  
Kolaparthi Venkatasubbarao ◽  
Lindsay Peterson ◽  
Shujie Zhao ◽  
Ping Hill ◽  
Lin Cao ◽  
...  

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769591 ◽  
Author(s):  
Wentao Zhou ◽  
Ning Ma ◽  
Hao Jiang ◽  
Yefei Rong ◽  
Yuezhen Deng ◽  
...  

Splicing factor 3b subunit 4, a critical component of pre-message RNA splicing complex, has been reported to play an important part in the tumorigenesis. However, the expression pattern and biological role of splicing factor 3b subunit 4 in pancreatic cancer have never been investigated. In this study, we found that both the messenger RNA ( p < 0.001) and protein level of splicing factor 3b subunit 4 were decreased significantly in pancreatic cancer specimens compared with their adjacent normal tissues. Overexpression of splicing factor 3b subunit 4 in pancreatic cancer cells inhibited cell growth and motility in vitro, while suppressing splicing factor 3b subunit 4 expression promoted the proliferation and migration of pancreatic cancer cells. In addition, splicing factor 3b subunit 4 was found to inhibit the activity of signal transducer and activator of transcription 3 signaling via downregulating the phosphorylation of signal transducer and activator of transcription 3 on a tyrosine residue at position 705. Taken together, these findings demonstrated that splicing factor 3b subunit 4 acted as a suppressive role in pancreatic cancer and indicated that restoring the function of splicing factor 3b subunit 4 might be a strategy for cancer therapy.


2020 ◽  
Author(s):  
Fiona Li ◽  
Edward Taylor ◽  
Ivan Yeung ◽  
David Jaffray ◽  
Ur Metser ◽  
...  

Abstract Purpose This study assessed the pharmacokinetics of the hypoxia PET tracer, [18F]fluoroazomycin arabinoside ([18F]FAZA), in pancreatic cancer (PCa) patients and determined the optimal kinetic parameters to distinguish cancerous from normal pancreatic tissue. Method Twenty patients with pancreatic ductal adenocarcinoma underwent dynamic [ 18 F]FAZA scans. The tissue time activity curve (TAC) was analyzed using graphical methods to determine reversibility of tracer binding and with standard compartment (S2TC) model and flow modified two tissue compartment (F2TC) model, developed to incorporate transit time of tracer through the blood vessel, to estimate the kinetic parameters. The optimal parameter set to distinguish hypoxic tumors from normal tissues was determined using logistic regression. Results Both graphical and kinetic model analysis indicated that tracer was reversibly bound. According to the Akaike Information Criteria, the F2TC model fitted the tumor TAC better than the S2TC model. Total distribution volume, V T , estimated by the F2TC model for both tumor and normal pancreatic tissue was not significant but that estimated by the S2TC model was significantly different from Logan graphical analysis. The extravascular distribution volume ( DV ) and tracer dissociation rate constant ( k 4 ) can classify hypoxic PCa from normal tissue with sensitivity of 95% and negative predictive value of 89% (P<0.01). Conclusions Kinetic analysis of dynamic [ 18 F]FAZA PET can distinguish PCa from normal tissue with high sensitivity. The reversibility of [ 18 F]FAZA binding in hypoxic cells could be due to glutathionylation of the nitroreductase reduced products and their subsequent efflux from same cells via the ATP mediated multidrug resistant protein (MRP-1) efflux pump.


Author(s):  
Kaka Renaldi ◽  
Teddy Septianto ◽  
Dadang Makmun

Background: Pancreatic cancer is a very rare cancer with age-adjusted rates ranging from about 5 to 10 new cases per 100,000 persons per year. It has one of the worst prognoses of any type of cancer, with a 5-year survival rate of only 4.6%. Several risk factors have been identified, including older age, smoking, familial history of pancreatic cancer, obesity, chronic pancreatitis, diabetes mellitus, and alcohol consumption.Method: This was a descriptive study describing the risk factors of patients who were diagnosed with pancreatic cancer in the period between 1 January 2014 – 1 January 2019 at the Cipto Mangunkusumo National Referral Hospital (RSCM) Jakarta. Data were obtained from the medical records and Endoscopic Retrograde Cholangiopancreatography (ERCP) database from the RSCM Gastrointestinal Endoscopy Center.Results: From January 2014 to January 2019 there were 123 patients with newly diagnosed pancreatic cancer in RSCM. The mean age was 52 years old. The incidence of pancreatic cancer is more common in men (53%) than women (47%). The most common risk factor identified is smoking which was found in 29% of patients, followed by obesity at 27.9% and a history of diabetes mellitus at 19.5%. Risk factors with a fairly low prevalence include alcohol consumption at 9.7% and chronic pancreatitis at 2.4%. No family history of pancreatic cancer is identified in any subject.Conclusion: Smoking, obesity, and diabetes mellitus are common risk factors in pancreatic cancer patients. In contrast, chronic pancreatitis, alcohol consumption, and family history of pancreatic cancer are less commonly identified in patients.


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