Pancreas最新文献

Objectives: Acute pancreatitis (AP) has a high incidence of hospitalizations, morbidity, and mortality worldwide. A growing number of studies on AP pathogenesis are based on cerulein-induced experimental model, which simulates human AP in vivo. It has been demonstrated that both pancreatic acinar cells and peritoneal macrophages are involved in pancreatic inflammation and damage. However, their connection has not been well understood.

Methods: A cerulein-induced AP model was established on the pancreatic acinar cell line AR42J. Rat macrophages were isolated from the peritoneal cavity. The effects of cerulein-induced pancreatic exosomes on the peritoneal macrophage and pancreas in vivo and in vitro were examined. The underlying molecular mechanism was investigated by exploring the regulatory role of downstream molecules.

Results: We found that exosomes derived from cerulein-treated AR42J cells induced rat peritoneal macrophage M1 polarization and pyroptosis. miR-24-3p was upregulated in cerulein-stimulated exosomes, whereas the miR-24-3p inhibitor counteracted the effect of pancreatic exosomes on peritoneal macrophage M1 polarization and pyroptosis. Furthermore, miR-24-3p inhibited March3 expression, whereas MARCH3 mediated NLRP3 ubiquitination in rat peritoneal macrophages, which, in turn, contributed to the apoptosis, reactive oxygen species production, and inflammation in AR42J cells.

Conclusions: Exosomes derived from cerulein-stimulated pancreatic acinar cells mediate peritoneal macrophage M1 polarization and pyroptosis via an miR-24-3p/MARCH3/NLRP3 axis in AP.

Background: Periampullary cancer (PAC) is highly aggressive with no effective adjuvant therapy or prognostic markers. Recently, poly (ADP-ribose) polymerase-1 (PARP-1) has emerged as a target in solid cancers, and its relationship with epithelial-mesenchymal transition (EMT) has been observed. However, the relationship between PARP-1 and EMT in PAC has not explored well.

Materials and methods: We assessed the prognostic significance of PARP-1 in 190 PACs patients and correlated it with EMT markers, including FGF8, FGFR4, MMP2, MMP3, Snail, and ZEB1. Immunohistochemistry for PARP-1 and EMT markers was performed using a tissue microarray.

Results: PARP-1 and FGF8 expression were associated with better survival unlike other solid cancers ( P = 0.006 and P = 0.003), and MMP3 and ZEB1 expression were associated with poor prognosis in multivariate and survival analyses ( P = 0.009 and P < 0.001). In addition, PARP-1 is related negatively to Snail but not related with other EMT markers, implying an independent mechanism between PARP-1 and EMT in PACs. PARP-1 and FGF8 are independent good survival markers in PACs unlike other solid cancers.

Conclusions: PARP-1 and FGF8 in PACs could not be related to the EMT pathway but must be rather understood in light of similar cancer-protective roles. Further studies are required on EMT-associated immune markers in PACs.

Objective: To study the effects of HSP70 on proliferation, migration, invasion, and epithelial-mesenchymal transformation (EMT) of pancreatic cancer cells and explore its underlying mechanisms.

Methods: Pancreatic cancer cell models with either reduced HSP70 or increased HSP70 expression were established. RT-qPCR and Western blot assays were used to determine mRNA and protein levels of HSP70, IKK/IκBa/NF-κB signaling pathway-related genes, and EMT markers. The CCK-8 and cell cloning assays were used to evaluate cell proliferation and cloning abilities. Transwell and wound healing assays were used to assess the invasive and migratory properties of the cells. Effects of NF-κB signaling modulation were explored using an IKK inhibitor (BAY11-7082) and an IKK overexpression vector (pCMV-IKK). Electrophoretic mobility shift assay (EMSA) and luciferase reporter assays were conducted to analyze NF-κB's promoter binding and transcriptional activities.

Results: HSP70 knockdown inhibited p-p65 nuclear translocation and reduced the expression of p-p65, p-IKKα/β, p-IκBα, N-cadherin, Vimentin, and Twist. It also decreased NF-κB's promoter binding and transcriptional activities, increased E-cadherin levels, and suppressed pancreatic cancer cell proliferation, cloning, migration, and invasion. In contrast, HSP70 overexpression led to increased expression of p-p65, p-IKKα/β, p-IκBα, N-cadherin, Vimentin, and Twist, decreased E-cadherin levels, and enhanced cell proliferation, cloning, migration, and invasion capabilities. NF-κB signaling pathway modulation reversed EMT changes induced by altered HSP70 expression levels. rhHSP70 also increased p-IKKα/β and p-IκBα protein levels.

Conclusion: HSP70 promotes the EMT and enhances pancreatic cancer cell proliferation, migration, and invasion by activating the NF-κB pathway.

Objectives: Standard ERCP sampling techniques for pancreaticobiliary malignancy have modest yields that could lead to delays in treatment. We aimed to evaluate whether combining EUS guided tissue acquisition (EUS-TA) with ERCP versus ERCP alone at the time of index procedure improved time to first outpatient evaluation and oncological treatment.

Methods: All patients without a prior pathological diagnosis who underwent index ERCP at Leeds Teaching Hospitals NHS Trust, United Kingdom, for malignant distal biliary obstruction from 2015 to 2020 were considered.

Results: A total of 292 patients were included, of whom 74.7% (n = 202) underwent EUS-TA/ERCP. A combined approach was more likely to establish a positive diagnosis (96.5% (n = 195) vs 57.8% (n = 52), p < 0.01) and less likely to require further sampling procedures (2.0% (n = 4) vs 17.8% (n = 16), p < 0.01). Mean times to first outpatient evaluation (16.9 vs 24.5 days (p = 0.01)) and oncological treatment (55.1 vs 79.3 days (p = 0.03)) were significantly shorter in the EUS-TA/ERCP group. A third (n = 86) of patients with a positive diagnosis did not receive oncological/surgical treatment.

Conclusions: In our cohort of patients, a combined approach was associated with improved diagnostic yield, reduced need for repeat sampling procedures and reduced time to evaluation and treatment, with similar therapeutic success and adverse event rates. Careful multidisciplinary discussion is recommended to avoid performing unnecessary EUS procedures on patients who will not benefit from further treatment.

Objectives: The aim of this study was to investigate how preoperative chemotherapy affected the serum zinc concentrations in patients with pancreatic cancer (PC).

Methods: Two hundreds and thirty-one patients with PC who underwent pancreatectomy at our department from 2013 to 2019 were enrolled in this study and measured for the serum zinc concentrations before pancreatectomy. Patient characteristics, course of treatment, and laboratory data were analyzed.

Results: One hundred thirty-five patients underwent upfront pancreatectomy and 58 received preoperative Gemcitabine + S1 (GEM + S1) and 29 received Gemcitabine + nab-Paclitaxel (GEM + nab-PTX). Comparing the serum zinc concentrations before and after preoperative treatment, it was found to decrease after treatment with statistical difference (79.3 μg/dl vs. 68.7 μg/dl, p < 0.001). The result was consistent with the investigation for both the patients who received GEM + S1 and those who received GEM + nab-PTX (p = 0.019, p < 0.001, respectively).

Conclusions: The preoperative chemotherapy consistently reduced the serum zinc concentrations in the PC patients, regardless of their regimen such as GEM + S1 and GEM + nab-PTX. Monitoring the serum zinc concentration and appropriate zinc supplementation may be essential for PC patients undergoing preoperative chemotherapy and pancreatectomy.

Background: To predict poor overall survival (OS) in pancreatic adenocarcinoma (PAC) who underwent FOLFIRINOX (5-fluorouracil/leucovorin/irinotecan/oxaliplatin) using clinical and computed tomography (CT) findings.

Methods: A total of 189 patients with PAC who received FOLFIRINOX were retrospectively included. Two reviewers assessed CT findings and resectability based on National Comprehensive Cancer Network guidelines. They determined tumor size changes according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Delta measurements were performed. Clinical results, such as whether to perform surgery, were also investigated. A Cox proportional hazard model was used to identify significant predictors for OS. A CT-based nomogram was constructed to predict OS.

Results: Seventy-four patients (39.2%) underwent surgery. For OS, rim enhancement of PAC on baseline CT (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.10-2.77; P = 0.018), high delta tumor on baseline CT (HR, 2.46; 95% CI, 1.55-3.91; P < 0.001), progressive disease at follow-up CT (HR, 8.89; 95% CI, 2.94-26.87; P < 0.001), and without surgery (HR, 2.81; 95% CI, 1.49-5.30; P = 0.001) were important features related to poor prognosis. The nomogram showed good predictive ability for the survival.

Conclusion: Both clinical and CT findings were useful for predicting OS after FOLFIRINOX in PAC.