pancreatic inflamation

BACKGROUND: Patients with resected pancreatic adenocarcinoma (PAAD) often experience short-term relapse and dismal survival, suggesting an urgent need to develop predictive and/or prognostic biomarkers for these populations. Given the potential associations of human leukocyte antigen class I (HLA-I) genotype with oncogenic mutational profile and immunotherapy efficacy, we aimed to assess whether differential HLA-I genotype could predict the postoperative outcomes in resected PAAD patients...

Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation...

The contribution of bone-marrow derived cells (BMCs) to a newly formed beta-cell population in adults is controversial. Previous studies have only used models of bone marrow transplantation from sex-mismatched donors (or other models of genetic labeling) into recipient animals that had undergone irradiation. This approach suffers from the significant shortcoming of the off-target effects of irradiation. Partial pancreatic duct ligation (PDL) is a mouse model of acute pancreatitis with a modest increase in beta-cell number...

PURPOSE: Pancreatic ductal adenocarcinoma (PDA) resists immunotherapy of adoptive cell transfer (ACT) and immune checkpoint inhibitors. Understanding the mechanisms underlying this resistance will improve PDA immunotherapy. This study investigated therapeutic effects and underlying mechanisms of anticoagulants on immunotherapy in PDA. EXPERIMENTAL DESIGN: The antitumor activity of immunotherapy was evaluated in mouse models of desert, excluded, and inflamed tumors...

BACKGROUND: Autoimmune pancreatitis (AIP) is a known mimicker of pancreatic ductal adenocarcinoma both clinically and radiologically. In this study, the authors present their institutional experience in diagnosing AIP on cytology and correlate results with the histologic findings. METHODS: A 14-year computerized search for patients who had histologically confirmed AIP with concurrent or prior cytology was performed. Clinical data, cytology findings, and surgical pathology results were reviewed for analysis...

AIMS/HYPOTHESIS: B cells play an important role in driving the development of type 1 diabetes; however, it remains unclear how they contribute to local beta cell destruction during disease progression. Here, we use gene expression profiling of B cell subsets identified in inflamed pancreatic tissue to explore their primary functional role during the progression of autoimmune diabetes. METHODS: Transcriptional profiling was performed on FACS-sorted B cell subsets isolated from pancreatic islets and the pancreatic lymph nodes of NOD mice...

BACKGROUND: FMNL3 (Formin-like protein 3) is involved in the tumorigenesis of multiple cancers. The critical role of FMNL3 in malignancies has been preliminarily explored, but its immunological correlation is not clear. METHODS: A pan-cancer analysis was performed to investigate the expressions, prognostic values, and immunological roles of FMNL3 across cancer types in The Cancer Genome Atlas (TCGA) database. Next, the correlations between FMNL3 and immunological features in the tumor microenvironment (TME) of pancreatic cancer (PAAD) were assessed...

We report a rare case of acute obstructive suppurative pancreatic ductitis (AOSPD) accompanied by duodenal obstruction in a patient with chronic pancreatitis (CP). A woman in her 40s was admitted to our hospital for intermittent abdominal distension, epigastric pain, and vomiting, which worsened during the previous 6 months. Gastroscopy showed incomplete pyloric obstruction, and computed tomography (CT) revealed calcification in the enlarged head of the pancreas, dilation of the main pancreatic duct (MPD), and thickening of both the gastric antrum and duodenal walls...

Poly zinc finger proteins (ZFP) that contain a KRAB (Krüppel-associated box) domain represent the largest class of transcription factors in higher organisms, but their roles in development and pathogenesis are largely undefined. ZFP14 (also known as ZNF531) contains thirteen zinc fingers and is highly conserved across species. Notably, we found that ZFP14 is frequently down-regulated in a multitude of human cancers, which correlates with poor prognosis of patients. Since ZFP14 has never been characterized, we generated a Zfp14-deficient mouse model to investigate the role of ZFP14 in development and pathogenesis...

BACKGROUND AND AIMS: There are limited data about the benign biliary strictures (BBS) which can develop during the clinical course of acute biliary pancreatitis (ABP) due to compression of the common bile duct (CBD) by edematous and inflamed pancreatic tissue. We aimed to determine the incidence of BBS due to ABP and its clinical course after endoscopic management. METHODS: The study was retrospectively conducted among patients with ABP who were admitted to a single tertiary reference center during 3 years...

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with a pleiotropic spectrum of biological functions implicated in the pathogenesis of cancer and inflammatory diseases. MIF is constitutively present in several cell types and non-lymphoid tissues and is secreted after acute stress or inflammation. MIF triggers the release of proinflammatory cytokines, overrides the anti-inflammatory effects of glucocorticoids, and exerts chemokine function, resulting in increased migration and recruitment of leukocytes into inflamed tissue...

PURPOSE: Advanced-stage gastrointestinal cancers represent a high unmet need requiring new effective therapies. We investigated the antitumor activity of a novel T cell-engaging antibody (B7-H6/CD3 ITE) targeting B7-H6, a tumor-associated antigen that is expressed in gastrointestinal tumors. EXPERIMENTAL DESIGN: Membrane proteomics and IHC analysis identified B7-H6 as a tumor-associated antigen in gastrointestinal tumor tissues with no to very little expression in normal tissues...

Ligand-targeting drug delivery systems have made significant strides for disease treatments with numerous clinical approvals in this era of precision medicine. Herein, we report a class of small molecule-based immune checkpoint-targeting maytansinoid conjugates. From the ligand targeting ability, pharmacokinetics profiling, in vivo anti-pancreatic cancer, triple-negative breast cancer, and sorafenib-resistant liver cancer efficacies with quantitative mRNA analysis of treated-tumor tissues, we demonstrated that conjugate 40a not only induced lasting regression of tumor growth, but it also rejuvenated the once immunosuppressive tumor microenvironment to an "inflamed hot tumor" with significant elevation of gene expressions that were not accessible in the vehicle-treated tumor...

Emphysematous pancreatitis (EP) is a rare variant of necrotizing pancreatitis which may result from bacterial superinfection of pancreatic tissue with gas-forming organisms such as Escherichia coli and Klebsiella pneumoniae . Gas formation is a consequence of mixed acid fermentation by these species, which may colonize the inflamed pancreatic tissue by intestinal translocation, hematogenous spread or direct seeding by penetrating ulcer. Previously described cases of EP associated with penetrating ulcer are exceedingly rare and typified by focal emphysema confined to the site of fistulation, often the head of pancreas...

Cancer-associated fibroblasts (CAFs) are orchestrators of the pancreatic ductal adenocarcinoma (PDAC) microenvironment. Previously we described four CAF subtypes with specific molecular and functional features. Here, we have refined our CAF subtype signatures using RNAseq and immunostaining with the goal to define bioinformatically the phenotypic stromal and tumor epithelial states associated with CAF diversity. We used primary CAF cultures grown from patient PDAC tumors, human datasets (in-house and public, including single-cell analyses), genetically engineered mouse PDAC tissues, and patient-derived xenografts (PDX) grown in mice...

BACKGROUND: Patients with acute idiopathic pancreatitis (AIP) should undergo further imaging tests such as endoscopic ultrasound (EUS) for further investigation. The time interval between an episode of AIP and EUS performance is still controversial. AIMS: We aimed to explore the optimal timing for performing EUS and to reveal parameters that might predict longer intervals needed for performing EUS. METHODS: We performed a single-center retrospective study at Galilee Medical Center from January 2015 to January 2020, at which point we included all patients who underwent EUS for further investigation of AIP...

Porphyromonas gingivalis is a keystone oral pathogen that successfully manipulates the human innate immune defenses, resulting in a chronic proinflammatory state of periodontal tissues and beyond. Here, we demonstrate that secreted outer membrane vesicles (OMVs) are deployed by P. gingivalis to selectively coat and activate human neutrophils, thereby provoking degranulation without neutrophil killing. Secreted granule components with antibacterial activity, especially LL-37 and myeloperoxidase (MPO), are subsequently degraded by potent OMV-bound proteases known as gingipains, thereby ensuring bacterial survival...

Aim: To briefly discuss the imaging features of different types of intra-abdominal fat necrosis. Background: Trauma and ischemic insult may result in intra-abdominal fat necrosis. Fat necrosis may present with acute abdomen, clinically simulating with other etiologies, such as acute diverticulitis and acute appendicitis. Main body: Imaging plays a crucial role in making the exact diagnosis and differentiating it from other pathologies that may require surgical intervention...

BACKGROUND: Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. However, the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined. METHODS: The expression of NAPSB in HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in patients with HCC using the Zhongnan cohort...

BACKGROUND: The molecular driving forces of anti-tumor immunity in pancreatic ductal adenocarcinoma (PDAC) remain unclear, which causing great difficulty in identifying an appropriate treatment strategy. AIMS: This study aims to explore the associations between expression of Wilms tumor 1-associated protein (WTAP) and effector T-cell infiltration in PDAC. METHODS: In this study, we explored the association between WTAP expression and infiltration level of CD8+ T cells in PDAC...