scholarly journals Pharmacokinetic Analysis of Dynamic [18F]FAZA PET Imaging in Pancreatic Cancer Patient

2020 ◽  
Author(s):  
Fiona Li ◽  
Edward Taylor ◽  
Ivan Yeung ◽  
David Jaffray ◽  
Ur Metser ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Kinetic Parameters ◽  
Normal Tissue ◽  
Pancreatic Tissue ◽  
Distribution Volume ◽  
Information Criteria ◽  
Pharmacokinetic Analysis ◽  
Time Activity ◽  
Normal Pancreatic Tissue ◽  
Pet Tracer

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.

CRM1 expression in pancreatic carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15115-e15115 ◽  
Author(s):  
Amit Mahipal ◽  
Domenico Coppola ◽  
Shilpa Gupta ◽  
Barbara Centeno ◽  
Mokenge Peter Malafa
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Carcinoma ◽  
Anticancer Agents ◽  
Normal Tissue ◽  
Tissue Sample ◽  
Pancreatic Tissue ◽  
Ductal Adenocarcinoma ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Paired Samples

e15115 Background: Increased expression of chromosomal region maintenance (CRM1) protein, also known as exportin 1, has been described in several human cancers. It is an important regulator of subcellular localization of tumor suppressor proteins and growth regulatory proteins. Direct inhibition of CRM1 blocks cell proliferation and induces apoptosis leading to the current evaluation of CRM1 inhibitors as anticancer agents in early phase clinical trials. There is a paucity of data regarding the prevalence of CRM1 expression in pancreatic cancer. Methods: We analyzed the expression of CRM1 by immunohistochemistry (IHC) in pancreatic tissue microarray (TMA) samples (malignant and non-malignant) obtained from patients who underwent potentially curative resection for pancreatic ductal adenocarcinoma. CRM1 antibody (Santa Cruz Biotechnology) was used for immunostaining the formalin fixed paraffin embedded core sections in the TMA samples. The intensity of staining and percentage of cells stained were graded on a scale of 0 to 3, with 3 being highest. The final IHC score was obtained using the product of immunostain intensity and percentage of cells stained (Range: 0-9). Low and high CRM1 expression was considered if the IHC score was 0 to 4 and 6 to 9 respectively. Results: Seventy nonmalignant and 91 pancreatic carcinoma samples were evaluated in this study. The median IHC score was 6 (range: 0-9) and 3 (range: 1-9) in malignant and nonmalignant pancreatic tissue samples respectively (P<0.0001). High CRM1 expression was found in 11% (8/70) of normal tissue samples and 69% (63/91) of tumor samples (P<0.0001). There were 48 paired samples of pancreatic cancer tissue and normal tissue obtained from same patient. Among these patients, 33 (69%) patients had higher CRM1 expression, 7 (15%) patients had similar expression and 8 (17%) patients had lower expression in malignant tissue sample as compared to their adjacent normal tissues. Conclusions: Higher CRM1 expression occurs frequently in pancreatic cancer as compared to nonmalignant pancreatic tissue, reinforcing its putative tumor oncogenic activity, and raising the value of targeting it for pancreatic cancer therapy.

scholarly journals LHPP suppresses proliferation, migration, and invasion and promotes apoptosis in pancreatic cancer

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Fahong Wu ◽  
Yanling Chen ◽  
Jinhai Zhu
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Tissue ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Normal Pancreatic Tissue ◽  
Phosphorylated Akt ◽  
Induced Apoptosis ◽  
Degree Of Differentiation ◽  
Cancer Tissues

Abstract Pancreatic cancer (PaCa) is a common malignant tumor of the digestive system with poor prognosis and no ideal treatment for inoperable patients, which is partly due to delayed diagnoses. It is recently reported that the protein histidine phosphatase LHPP is a tumor suppressor in hepatocellular carcinoma, cervical cancer, and bladder cancer. So far, there is no study on the expression level of LHPP in PaCa, and its mechanism of action on tumors is unclear. In this experiment, LHPP expression was lower in cancer tissues than that in normal pancreatic tissue, and clinicopathological results showed that LHPP expression was correlated with the degree of differentiation and lymphatic metastasis of pancreatic carcinoma. The biological characteristics of LHPP in PaCa cells were examined by the cell counting kit-8 assay, transwell assay, and monoclonal formation test. The inhibitory mechanism of LHPP in PaCa cells was determined using Western blotting and flow cytometry. The results showed that LHPP restrained PaCa cell proliferation, migration, and invasion. Increased LHPP expression promoted the apoptosis of PaCa cells through higher activation of cleaved-PARP and cleaved-Casp3 and lower activation of cIAP1. Importantly, the increase in LHPP enhanced PTEN expression and decreased the phosphorylated AKT level. Moreover, LHPP-induced apoptosis was diminished by SC79 (AKT activator) in PaCa cells. In conclusion, LHPP blocks proliferation, migration, and invasion and enhances apoptosis in PaCa cells through the PTEN/AKT signaling pathway.

scholarly journals Deep learning-based gene selection in comprehensive gene analysis in pancreatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yasukuni Mori ◽  
Hajime Yokota ◽  
Isamu Hoshino ◽  
Yosuke Iwatate ◽  
Kohei Wakamatsu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Deep Learning ◽  
Gene Selection ◽  
Pancreatic Tissue ◽  
Expression Data ◽  
Tissue Samples ◽  
Normal Pancreatic Tissue ◽  
Model Training ◽  
Selection Of

AbstractThe selection of genes that are important for obtaining gene expression data is challenging. Here, we developed a deep learning-based feature selection method suitable for gene selection. Our novel deep learning model includes an additional feature-selection layer. After model training, the units in this layer with high weights correspond to the genes that worked effectively in the processing of the networks. Cancer tissue samples and adjacent normal pancreatic tissue samples were collected from 13 patients with pancreatic ductal adenocarcinoma during surgery and subsequently frozen. After processing, gene expression data were extracted from the specimens using RNA sequencing. Task 1 for the model training was to discriminate between cancerous and normal pancreatic tissue in six patients. Task 2 was to discriminate between patients with pancreatic cancer (n = 13) who survived for more than one year after surgery. The most frequently selected genes were ACACB, ADAMTS6, NCAM1, and CADPS in Task 1, and CD1D, PLA2G16, DACH1, and SOWAHA in Task 2. According to The Cancer Genome Atlas dataset, these genes are all prognostic factors for pancreatic cancer. Thus, the feasibility of using our deep learning-based method for the selection of genes associated with pancreatic cancer development and prognosis was confirmed.

scholarly journals ppENKGene Methylation Status in the Development of Pancreatic Carcinoma

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Lixin Yang ◽  
Hong Yang ◽  
Jingnan Li ◽  
Jianyu Hao ◽  
Jiaming Qian
Keyword(s):  
Pancreatic Cancer ◽  
Mrna Expression ◽  
Pancreatic Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Methylation Status ◽  
Pancreatic Tissue ◽  
Human Pancreatic Cancer ◽  
Normal Pancreatic Tissue ◽  
Carcinoma Cell Lines

Objective. To explore the association of hypermethylation of the proenkephalin gene (ppENK) with pancreatic carcinoma and to identify the effects of a demethylating agent on pancreatic cell lines.Method. Human pancreatic cancer tissues and five pancreatic carcinoma cell lines, as well as normal pancreatic tissue, were used.ppENKmethylation status was detected by MS-PCR (methylation-specific PCR).Results. Methylation ofppENKwas detected in 90.3% (28/31) of the human pancreatic carcinoma tissues but was not seen in normal pancreatic tissue. There was no correlation between the extent of methylation ofppENKand the clinicopathological features of the pancreatic carcinomas. MethylatedppENKwas detected in all the pancreatic cancer cell lines and was associated with loss of mRNA expression in the pancreatic carcinoma cell lines and normal pancreatic tissue. After treatment with 5-aza-dC, methylatedppENKwas not detected and the inhibition ofppENKmRNA expression was reversed.Conclusions. Inhibition ofppENKexpression by a change in its methylation status plays an important role in pancreatic carcinogenesis.ppENKmethylation is thus an important molecular event that distinguishes pancreatic carcinoma tissue from normal pancreatic tissue. Effects on cell growth, apoptosis, and the cell cycle may contribute to changes ofppENKmethylation status.

scholarly journals Comparison of different kinetic models for dynamic 68Ga-FAPI-04 PET/CT imaging of hepatocellular carcinoma with various, also dual-blood input function

2020 ◽  
Author(s):  
Barbara Katharina Geist ◽  
Haiqun Xing ◽  
Jingnan Wang ◽  
Ximin Shi ◽  
Haitao Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinetic Parameters ◽  
Dynamic Model ◽  
Kinetic Models ◽  
Compartment Model ◽  
Input Function ◽  
Information Criteria ◽  
Model Parameters ◽  
Time Activity ◽  
Two Compartment Model

Abstract Aim: The aim of the study is to establish a 68Ga-FAPI-04 dynamic model in hepatic lesions, to determine the potential role of kinetic parameters in the differentiation of hepatocellular carcinoma (HCC) from non-HCC lesions.Methods: 68Ga-FAPI-04 PET dynamic images of 7 HCC lesions and 5 non-HCC lesions from 8 patients were analyzed from their time-activity curve (TACs). Five kinetic models were applied to the TACs, using hepatic artery and/or portal vein as input functions. Results were analyzed according to Akaike and Schwartz information criteria.Results: A two-compartment model using solely a venous input function was most preferred and showed significant differences between healthy regions and lesions in almost all model parameters. Using a two-compartment model with one arterial input function delivered significant differences between HCC and non-HCC regions in the case of K1 (p = 0.03).Conclusion: The established FAPI PET dynamic model in liver lesions suggested that FAPI PET kinetic parameters have the potential to differentiate between HCC and non-HCC lesions.

Signal transducer and activator of transcription 3β in pancreatic cancer

2010 ◽  
Vol 5 (4) ◽  
pp. 435-438
Author(s):  
Agnieszka Dettlaff-Pokora ◽  
Justyna Kostro
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Cancer Patients ◽  
Pancreatic Tissue ◽  
Signal Transducer ◽  
Neoplastic Tissue ◽  
Normal Pancreatic Tissue ◽  
Normal Tissues ◽  
Proliferation And Apoptosis ◽  
Transcription 3

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.

scholarly journals Association of γ-aminobutyric acid type A receptor-associated protein with prognosis in patients after radical pancreatic cancer treatment

2020 ◽  
Author(s):  
Chao Zhang ◽  
Wenhao Tang ◽  
Yanyuan Tu ◽  
Zurong Yuan ◽  
Wei Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cox Regression ◽  
Pancreatic Tissue ◽  
Postoperative Adjuvant Chemotherapy ◽  
Normal Pancreatic Tissue ◽  
Free Survival ◽  
Patient Prognosis ◽  
Cancer Tissues

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.

scholarly journals A Methodological Investigation of Healthy Tissue, Hepatocellular Carcinoma and other Lesions with Dynamic 68Ga-FAPI-04 PET/CT Imaging

2020 ◽  
Author(s):  
Barbara Katharina Geist ◽  
Haiqun Xing ◽  
Jingnan Wang ◽  
Ximin Shi ◽  
Haitao Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinetic Model ◽  
Kinetic Parameters ◽  
Input Function ◽  
Information Criteria ◽  
Healthy Tissue ◽  
Model Parameters ◽  
Time Activity ◽  
Tissue Compartment ◽  
Pet Scans

Abstract Background: The study aimed to establish a 68Ga-FAPI-04 kinetic model in hepatic lesions, to determine the potential role of kinetic parameters in the differentiation of hepatocellular carcinoma (HCC) from non-HCC lesions.Material and Methods: Time activity curves (TACs) were extracted from seven HCC lesions and five non-HCC lesions obtained from 68Ga-FAPI-04 dynamic positron emission tomography (PET) scans of eight patients. Three kinetic models were applied to the TACs, using image derived hepatic artery and/or portal vein as input functions. For input functions and the lesions, the according voxel with the maximum standardized uptake value (SUVmax) was taken, for the healthy tissue mean SUV values. The optimum model was chosen after applying the Schwartz information criteria to the TACs, differences in model parameters between HCC, non-HCC lesions, and healthy tissue were evaluated with the ANOVA test. Results: A reversible two-tissue compartment model using both the arterial as well as venous input function was most preferred and showed significant differences in the kinetic parameters VND, VT and BPND between HCC, non-HCC lesions and healthy regions (p < 0.01). Conclusion: Several Model parameters derived from a two-tissue compartment kinetic model with two image-derived input function from vein and aorta and using SUVmax allow a differentiation between HCC and non-HCC lesions, obtained from dynamically performed PET scans using FAPI.

scholarly journals Vascularisation Pattern of Chronic Pancreatitis Compared with Pancreatic Carcinoma: Results from Contrast-Enhanced Endoscopic Ultrasound

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Michael Hocke ◽  
Christoph F. Dietrich
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Pancreatic Carcinoma ◽  
Endoscopic Ultrasound ◽  
Clinical Medicine ◽  
Pancreatic Tissue ◽  
Mechanical Index ◽  
Contrast Enhanced ◽  
Inflammatory Processes ◽  
Doppler Techniques

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.

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