The Potential Effect of Proteasome Inhibitor PS-341 on Severe Acute Pancreatitis Detected by Positron Emission Tomography in ICR Mice

Dong, Xin; Zhan, Yin Chu; Jiang, Ren Ya; Xie, Qiu; Peng, Jingjing; Wang, Jing; Gao, Shun Liang; Wu, Yu

doi:10.1016/j.jss.2009.06.011

Cited by 7 publications

(4 citation statements)

References 48 publications

(58 reference statements)

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“…19 Similar to von Forstner et al using 18 F-FDG in PDAC orthotopic tumors 30 we found a low uptake of 18 F-FDG in orthotopic AsPC-1 tumors contrasting with the good detection of tumor on PET images with 68 Ga-DOTA-NT-20.3 only 14 days after cells' implantation. As reported by Dong et al we have evaluated the extent and quantification of pancreatic inflammation in mice using small animal 18 F-FDG-PET 31 and, as expected, the in situ inflammatory response was visible on 18 F-FDG PET but not on 68 Ga-DOTA-NT-20.3. This result was concordant with the histological observation of pancreatic edema, infiltration by inflammatory cells in close contact with acini and fibrosis, but no detection of NTSR1 expression.…”

Section: Molecular Pharmaceuticssupporting

confidence: 60%

Preclinical Evaluation of ⁶⁸Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis

et al. 2019

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Neurotensin receptor 1 (NTSR1) is overexpressed in human pancreatic ductal adenocarcinoma (PDAC). Specific noninvasive positron-emission tomography (PET) imaging probes may improve the diagnostic accuracy and the monitoring of therapy for patients with PDAC. Here, we report the use of the 68 Ga-labeled neurotensin (NTS) analogue DOTA-NT-20.3 to image human PDAC in animal models and to discriminate tumors from pancreatitis. In addition to the preclinical study, two tissue microarray slides, constructed by small core biopsies (2−5) from standard paraffin-embedded tumor tissues, were used to confirm the high (78%) positivity rate of NTSR1 expression in human PDAC. PET imaging, biodistribution, blocking, and histology studies were performed in subcutaneous AsPC-1 pancreatic tumor-bearing mice. 68 Ga-DOTA-NT-20.3 PET images showed rapid tumor uptake and high contrast between the tumor and background with a fast blood clearance and a moderate accumulation in the kidneys. Ex vivo biodistribution showed low uptake in normal pancreas (0.22% IA/g) and in the remaining organs at 1 h postinjection, kidney retention (5.38 ± 0.54% IA/g), and fast clearance from blood and confirmed high uptake in tumors (5.28 ± 0.93% IA/g), leading to a tumor-to-blood ratio value of 6 at 1 h postinjection. The significant decrease of tumor uptake in a blocking study demonstrated the specificity of 68 Ga-DOTA-N-T20.3 to target NTSR1 in vivo. PET imaging was also conducted in an orthotopic xenograft model that allows tumors to grow in their native microenvironment and in an experimental pancreatitis model generated by caerulein injections. As opposed to 2-[ 18 F]fluoro-deoxyglucose, 68 Ga-DOTA-NT-20.3 distinguishes PDAC from pancreatitis. Thus, 68 Ga-DOTA-NT-20.3 is a promising PET imaging probe for imaging PDAC in humans.

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Section: Molecular Pharmaceuticssupporting

confidence: 60%

Preclinical Evaluation of ⁶⁸Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis

et al. 2019

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“…In the current study, the authors did not identify which cell underwent inhibition of NFkB by PS-341 [8]. It is very possible that the inhibition of NFkB in the infiltrating inflammatory cells rather than pancreatic acinar cells was the mechanism that decreased inflammation in SAP.…”

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confidence: 63%

A Proteasome Inhibitor to Treat Acute Pancreatitis? Maybe…

Huan

Zenilman

2010

Journal of Surgical Research

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“…Dong X et al illustrated in their study that the proteasome inhibitor PS-341 effectively mitigated the severity of acute pancreatitis induced by cerulein and lipopolysaccharide in mice. This observed effect is attributed to the inhibition of NF-κB activation, leading to improvements in various parameters, including serum amylase, CRP, lactate dehydrogenase, IL-1β, IL-6, and pancreatic MPO levels ( Dong et al, 2010 ). Similarly, Zhu QT documented that the proteasome plays a role in the development of AP and that its inhibitor, bortezomib, demonstrated protective effects against AP in mice by reducing the expression of NF-κB p65 nucleoprotein and total proteasome 20S protein ( Zhu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and analysis of chemokine-related and NETosis-related genes in acute pancreatitis to develop a predictive model

Mo,

Wu,

Luo

et al. 2024

Front. Genet.

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Background: Chemokines and NETosis are significant contributors to the inflammatory response, yet there still needs to be a more comprehensive understanding regarding the specific molecular characteristics and interactions of NETosis and chemokines in the context of acute pancreatitis (AP) and severe AP (SAP).Methods: To address this gap, the mRNA expression profile dataset GSE194331 was utilized for analysis, comprising 87 AP samples (77 non-SAP and 10 SAP) and 32 healthy control samples. Enrichment analyses were conducted for differentially expressed chemokine-related genes (DECRGs) and NETosis-related genes (DENRGs). Three machine-learning algorithms were used for the identification of signature genes, which were subsequently utilized in the development and validation of nomogram diagnostic models for the prediction of AP and SAP. Furthermore, single-gene Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed. Lastly, an interaction network for the identified signature genes was constructed.Results: We identified 12 DECRGs and 7 DENRGs, and enrichment analyses indicated they were primarily enriched in cytokine-cytokine receptor interaction, chemokine signaling pathway, TNF signaling pathway, and T cell receptor signaling pathway. Moreover, these machine learning algorithms finally recognized three signature genes (S100A8, AIF1, and IL18). Utilizing the identified signature genes, we developed nomogram models with high predictive accuracy for AP and differentiation of SAP from non-SAP, as demonstrated by area under the curve (AUC) values of 0.968 (95% CI 0.937–0.990) and 0.862 (95% CI 0.742–0.955), respectively, in receiver operating characteristic (ROC) curve analysis. Subsequent single-gene GESA and GSVA indicated a significant positive correlation between these signature genes and the proteasome complex. At the same time, a negative association was observed with the Th1 and Th2 cell differentiation signaling pathways.Conclusion: We have identified three genes (S100A8, AIF1, and IL18) related to chemokines and NETosis, and have developed accurate diagnostic models that might provide a novel method for diagnosing AP and differentiating between severe and non-severe cases.

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The Potential Effect of Proteasome Inhibitor PS-341 on Severe Acute Pancreatitis Detected by Positron Emission Tomography in ICR Mice

Cited by 7 publications

References 48 publications

Preclinical Evaluation of ⁶⁸Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis

Preclinical Evaluation of ⁶⁸Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis

A Proteasome Inhibitor to Treat Acute Pancreatitis? Maybe…

Identification and analysis of chemokine-related and NETosis-related genes in acute pancreatitis to develop a predictive model

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The Potential Effect of Proteasome Inhibitor PS-341 on Severe Acute Pancreatitis Detected by Positron Emission Tomography in ICR Mice

Cited by 7 publications

References 48 publications

Preclinical Evaluation of 68Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis

Preclinical Evaluation of 68Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis

A Proteasome Inhibitor to Treat Acute Pancreatitis? Maybe…

Identification and analysis of chemokine-related and NETosis-related genes in acute pancreatitis to develop a predictive model

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Preclinical Evaluation of ⁶⁸Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis

Preclinical Evaluation of ⁶⁸Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis