Early studies indicated that the androgen receptor (AR) might play important roles in the regulating of the initiation and progression of hepatocellular carcinoma (HCC), but its linkage to the ...surrounding macrophages and their impacts on the HCC progression remain unclear. Here we found that macrophages in liver cancer might function via altering the microRNA, miR-92a-2-5p, in exosomes to decrease liver cancer cells AR expression, which might then lead to increase the liver cancer cells invasion. Mechanism dissection revealed that miR-92a-2-5p from the exosomes could target the 3'UTR of AR mRNA to suppress AR translation, altering the PHLPP/p-AKT/β-catenin signaling to increase liver cancer cells invasion. Preclinical studies demonstrated that targeting this newly identified signaling with miR-92a-2-5p inhibitors led to suppress liver cancer progression. Together, these findings suggest that macrophages in the liver cancer tumor microenvironment may function via exosomes to regulate liver cancer progression, and targeting this newly identified macrophages/exosomes-miR-92a-2-5p/AR/PHLPP/p-AKT/β-catenin signaling may help in the development of novel treatment strategies to better suppress liver cancer progression.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hepatocellular carcinoma (HCC) is a malignant tumor with a high degree of malignancy and a poor prognosis. Androgen receptor (AR) has been reported to play important roles in the regulation of the ...progression of HCC, but the underlying mechanisms of how AR regulates HCC initiation, progression, metastasis, and chemotherapy resistance still need further study. Our study found that AR could act as a tumor suppression gene to suppress HCC cells invasion and migration capacities
miR-122-5p/RABL6 signaling, and the mechanism study further confirmed that miR-122-5p could suppress the expression of RABL6 to influence HCC cells progression by directly targeting the 3'UTR of the mRNA of RABL6. The preclinical study using an
mouse model with orthotopic xenografts of HCC cells confirmed the
data, and the clinical data gotten from online databases based on TCGA samples also confirmed the linkage of AR/miR-122-5p/RABL6 signaling to the HCC progression. Together, these findings suggest that AR could suppress HCC invasion and migration capacities
miR-122-5p/RABL6 signaling, and targeting this newly explored signaling may help us find new therapeutic targets for better treatment of HCC.
Functioning tumors are usually diagnosed during the early evaluation of hormonal syndromes, whereas most non-functioning pNENs are accidentally found during imaging studies and endoscopies for other ...complaints, such as the mass effect of local growth or secondary symptoms owing to metastasis. 4,5 Although most pNENs are sporadic and likely carry somatic mutations in death domain-associated protein 6 (DAXX) and ATP-dependent helicase (ATRX),6 they may develop in patients with hereditary endocrinopathies, including multiple endocrine neoplasia type 1 (MEN1),7 von Hippel–Lindau (VHL) syndrome,8 neurofibromatosis type 1 (NF1),9 and Tuberous Sclerosis Complex (TSC). Laboratory tests Peripheral blood biomarker test Serum chromogranin A (CgA), the most critical universal biomarker for neuroendocrine tumors (NETs), is used to assist in diagnosis and to assess the response and prognosis. Percutaneous transhepatic portal vein catheterization (PT-PC), which involves placing the catheter into the splenic vein and portal vein trunk to measure VIP concentrations, facilitates qualitative assessment and localization evaluation.
Postoperative pancreatic fistula (POPF) is the most common critical complication after pancreatoduodenectomy (PD) and is the primary reason for increased mortality and morbidity after PD. We aim to ...investigate the clinical significance of a novel approach, i.e., end-to-side one-layer continuous pancreaticojejunostomy, for patients with PD.
The clinical data of 65 patients who underwent pancreatoduodenectomy at the Xiangya Hospital, Central South University, from September 2020 to December 2021 were retrospectively analyzed.
Forty patients underwent end-to-end invaginated pancreaticojejunostomy, and 25 underwent the novel end-to-side one-layer continuous pancreaticojejunostomy. No significant differences were observed in pancreatic fistula, intraperitoneal infection, intraperitoneal bleeding, reoperation, postoperative hospital stay, or perioperative death between the two groups. However, the novel end-to-side one-layer continuous pancreaticojejunostomy group had significantly shorter operation duration (32.6 ± 5.1 min vs. 8.3 ± 2.2 min,
< 0.001). The incidence of pancreatic fistula in the novel pancreaticojejunostomy group was 12%, including two cases of grade A POPF and only one case of grade B POPF. No cases of grade C POPF occurred. No deaths were observed during the perioperative period.
The novel anastomosis method leads to a shorter operation duration than the traditional anastomosis method and does not increase postoperative complications. In conclusion, it is a simplified and feasible method for pancreatic anastomosis.
Pancreatic cancer (PC) is one of the most aggressive types of cancer with an extremely poor prognosis. Invasive growth and early metastasis is one of the greatest challenges to overcome for the ...treatment of PC. Numerous previous studies have indicated that the transcription factor Krüppel-like factor 8 (KLF8) and nuclear cofactor four and a half LIM-only protein 2 (FHL2) serve important roles in tumorigenesis and tumor progression; however, their roles in PC remain elusive. The present study revealed that KLF8 and FHL2 expression is aberrantly co-overexpressed in PC tissue samples and associated with tumor metastasis. Furthermore, a positive correlation between the expression levels of KLF8 and FHL2 was observed. Subsequently, the present study identified KLF8 as a critical inducer of epithelial-to-mesenchymal transition (EMT) and invasion. Of note, the present study demonstrated that KLF8 overexpression induced a strong increase in FHL2 expression, and subsequent promoter reporter assays determined that KLF8 directly bound and activated the FHL2 gene promoter. Furthermore, FHL2 knockdown in KLF8-overexpressing cells partially reversed the EMT and invasive phenotypes. The present study identified KLF8-induced FHL2 activation as a novel and critical signaling mechanism underlying human PC invasion.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
MicroRNAs are -22 nucleotide RNAs processed from RNA hairpin structures that play important roles in regulating protein expression level via binding to mRNA, either suppressing its translation or ...speeding up its degradation. In humans, they regulate most protein-coding genes, including genes important in cancer and other diseases. In this study, the expression of microRNA-140 （miR-140） was demonstrated to be significantly suppressed in pancreatic duct adenocarcinoma spe- cimens and cell lines, compared with their adjacent normal tissues. With the help of bioinformatics analysis, inhibitor of apoptosis-stimulating protein of p53 （iASPP） was identified to be a direct target of miR-140, and luciferase reporter experiment confirmed this discovery. Overexpression of miR-140 decreases the protein expressions of iASPP, ANp63, MMP2, and MMP9. Growth and invasion of PANC-1 cells were attenuated by overexpression of miR-140 in vitro. The suppressive effect of miR-140 on PANC-1 cell line could be partly balanced out by manual overexpression of iASPP. Above all, these findings provided insights into the functional mechanism of miR-140, suggested that the miR-140/iASPP axis may interfere with the proliferative and invasive property of pancreatic duct adenocarcinoma cells, and indicated that miR-140 could be a potential therapeutic target for pancreatic duct adenocarcinoma.
Objective Elevated pre-operative C-reactive protein (CRP) serum values have been reported to be associated with poor overall survival for patients with pancreatic neuroendocrine neoplasms (pNEN). The ...aim of this study was to identify mechanisms linking CRP to poor prognosis in pNEN. Methods The malignant properties of pNENs were investigated using the human pNEN cell-lines BON1 and QGP1 exposed to CRP or IL-6. Analyses were performed by ELISA, Western blot, flow cytometry and immunocytochemistry as well as invasion and proliferation assays. To compare cytokine profiles and CRP levels, 76 serum samples of pNEN patients were analyzed using Luminex technology. In parallel, the expression of CRP and growth signaling pathway proteins was assessed on cell lines and paraffin-embedded primary pNEN. Results In BON1 and QGP1 cells, inflammation (exposure to IL-6) significantly upregulated CRP expression and secretion as well as migratory properties. CRP stimulation of BON1 cells increased IL-6 secretion and invasion. This was accompanied by activation/phosphorylation of the ERK, AKT and/or STAT3 pathways. Although known CRP receptors – CD16, CD32 and CD64 – were not detected on BON1 cells, CRP uptake of pNEN cells was shown after CRP exposure. In patients, increased pre-operative CRP levels (≥5 mg/L) were associated with significantly higher serum levels of IL-6 and G-CSF, as well as with an increased CRP expression and ERK/AKT/STAT3 phosphorylation in pNEN tissue. Conclusion The malignant properties of pNEN cells can be stimulated by CRP and IL-6 promoting ERK/AKT/STAT pathways activation as well as invasion, thus linking systemic inflammation and poor prognosis.
Background
The extent of pancreatoduodenectomy for pancreatic head cancer remains controversial, and more high‐level clinical evidence is needed. This study aimed to evaluate the outcome of extended ...pancreatoduodenectomy (EPD) with retroperitoneal nerve resection in pancreatic head cancer.
Methods
This multicenter randomized trial was performed at 6 Chinese high‐volume hospitals that enrolled patients between October 3, 2012, and September 21, 2017. Four hundred patients with stage I or II pancreatic head cancer and without specific pancreatic cancer treatments (preoperative chemotherapy or chemoradiation) within three months were randomly assigned to undergo standard pancreatoduodenectomy (SPD) or EPD, with the latter followed by dissection of additional lymph nodes (LNs), nerves and soft tissues 270° on the right side surrounding the superior mesenteric artery and celiac axis. The primary endpoint was overall survival (OS) by intention‐to‐treat (ITT). The secondary endpoints were disease‐free survival (DFS), mortality, morbidity, and postoperative pain intensity.
Results
The R1 rate was slightly lower with EPD (8.46%) than with SPD (12.56%). The morbidity and mortality rates were similar between the two groups. The median OS was similar in the EPD and SPD groups by ITT in the whole study cohort (23.0 vs. 20.2 months, P = 0.100), while the median DFS was superior in the EPD group (16.1 vs. 13.2 months, P = 0.031). Patients with preoperative CA19–9 < 200.0 U/mL had significantly improved OS and DFS with EPD (EPD vs. SPD, 30.8 vs. 20.9 months, P = 0.009; 23.4 vs. 13.5 months, P < 0.001). The EPD group exhibited significantly lower locoregional (16.48% vs. 35.20%, P < 0.001) and mesenteric LN recurrence rates (3.98% vs. 10.06%, P = 0.022). The EPD group exhibited less back pain 6 months postoperation than the SPD group.
Conclusions
EPD for pancreatic head cancer did not significantly improve OS, but patients with EPD treatment had significantly improved DFS. In the subgroup analysis, improvements in both OS and DFS in the EPD arm were observed in patients with preoperative CA19–9 < 200.0 U/mL. EPD could be used as an effective surgical procedure for patients with pancreatic head cancer, especially those with preoperative CA19–9 < 200.0 U/mL.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In clinical practice, pancreatic neuroendocrine neoplasms (pNENs) with a diameter smaller than 2 cm are commonly referred to as small pNENs. Due to their generally favorable biological ...characteristics, the diagnosis and treatment of small pNENs differ from other pNENs and are somewhat controversial. In response to this, the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association have developed a consensus on the diagnosis and treatment of small pNENs, which is based on evidence-based medicine and expert opinions. This consensus covers various topics, including concepts, disease assessment, treatment selection, follow-up, and other relevant aspects.
Abstract
Acute pancreatitis (AP) is a common acute abdominal condition of the digestive system. In recent years, treatment concepts, methods, and strategies for the diagnosis of AP have advanced, and ...this has played an important role in promoting the standardization of AP diagnosis and treatment and improving the treatment quality of AP patients. On the basis of previous guidelines and expert consensus, this guideline adopts an evidence-based, problem-based expression; synthesizes important clinical research data at home and abroad in the most recent 5 years; and forms 29 recommendations through multidisciplinary expert discussion, including diagnosis, treatment, and follow-up. It is expected to provide evidence support for the treatment of AP in the clinical setting in China.
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