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Cell Proliferation Dec 2023Having been reported to be a crucial prognostic factor in solid tumours, the role of high endothelial venule (HEV) in intrahepatic cholangiocarcinoma (ICC) remains...
Having been reported to be a crucial prognostic factor in solid tumours, the role of high endothelial venule (HEV) in intrahepatic cholangiocarcinoma (ICC) remains unclear, however. The data of ICC and healthy individuals were downloaded from the Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases. Meanwhile, a cutting-edge ICC high-resolution spatial transcriptome was also acquired before these data were comprehensively analysed using bioinformatics approaches. Moreover, 95 individuals with ICC who had undergone resection surgery were enrolled in this study to investigate the relationship between HEV and tumour microenvironment (TME) applying immunohistochemistry and multiple immunofluorescence techniques. The high-HEV subtype contains rich immune infiltrates including tertiary lymphoid structure (TLS), CD8+ T cells, and CD20+ B cells. Furthermore, HEV and TLS exhibited a strong relationship of spatial colocalization. Correlated with improved prognostic outcomes in ICC, the high-HEV subtype could be an independent prognostic indicator for individuals with ICC. This study revealed the association of HEV with immune function and observed a strong spatial colocalization correlation between HEV and TLS. Moreover, correlated with immunotherapeutic response, HEV could improve prognostic outcomes, which may be a potential indicator of immunotherapy pathology in ICC.
Topics: Humans; Prognosis; Venules; Cholangiocarcinoma; Biomarkers; Bile Ducts, Intrahepatic; Bile Duct Neoplasms; Tumor Microenvironment
PubMed: 37401015
DOI: 10.1111/cpr.13513 -
ELife Oct 2023The splicing factor SF3B1 is recurrently mutated in various tumors, including pancreatic ductal adenocarcinoma (PDAC). The impact of the hotspot mutation SF3B1 on the...
The splicing factor SF3B1 is recurrently mutated in various tumors, including pancreatic ductal adenocarcinoma (PDAC). The impact of the hotspot mutation SF3B1 on the PDAC pathogenesis, however, remains elusive. Here, we demonstrate that Sf3b1 alone is insufficient to induce malignant transformation of the murine pancreas, but that it increases aggressiveness of PDAC if it co-occurs with mutated KRAS and p53. We further show that Sf3b1 already plays a role during early stages of pancreatic tumor progression and reduces the expression of TGF-β1-responsive epithelial-mesenchymal transition (EMT) genes. Moreover, we found that SF3B1 confers resistance to TGF-β1-induced cell death in pancreatic organoids and cell lines, partly mediated through aberrant splicing of . Overall, our findings demonstrate that SF3B1 acts as an oncogenic driver in PDAC, and suggest that it promotes the progression of early stage tumors by impeding the cellular response to tumor suppressive effects of TGF-β.
Topics: Animals; Humans; Mice; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Mutation; Pancreatic Ducts; Pancreatic Neoplasms; Phosphoproteins; RNA Splicing Factors; Transcription Factors; Transforming Growth Factor beta1
PubMed: 37823551
DOI: 10.7554/eLife.80683 -
Gastroenterology Report 2023Endoscopic ultrasound (EUS) has become an indispensable modality for the assessment of the gastrointestinal tract and adjacent structures since its origin in the 1980s.... (Review)
Review
Endoscopic ultrasound (EUS) has become an indispensable modality for the assessment of the gastrointestinal tract and adjacent structures since its origin in the 1980s. Following the development of the linear echoendoscope, EUS has evolved from a purely diagnostic modality to a sophisticated tool for intervention, with numerous luminal, pancreaticobiliary, and hepatic applications. Broadly, these applications may be subdivided into three categories: transluminal drainage or access procedures, injection therapy, and EUS-guided liver interventions. Transluminal drainage or access procedures include management of pancreatic fluid collection, EUS-guided biliary drainage, EUS-guided bile duct drainage, EUS-guided pancreatic duct drainage, and enteral anastomosis formation. Injection therapies include therapeutic EUS-guided injections for management of malignancies accessible by EUS. EUS-guided liver applications include EUS-guided liver biopsy, EUS-guided portal pressure gradient measurement, and EUS-guided vascular therapies. In this review, we discuss the origins of each of these EUS applications, evolution of techniques leading to the current status, and future directions of EUS-guided interventional therapy.
PubMed: 37398926
DOI: 10.1093/gastro/goad038 -
Diagnostics (Basel, Switzerland) Oct 2023Embryological development of the pancreas is a complex phenomenon and, therefore, it can have multiple developmental aberrations. Fortunately, the majority of these... (Review)
Review
Embryological development of the pancreas is a complex phenomenon and, therefore, it can have multiple developmental aberrations. Fortunately, the majority of these pancreatic ductal anomalies are asymptomatic with no clinical relevance and are incidentally detected during diagnostic cross-sectional imaging or endoscopic retrograde cholangiopancreatography (ERCP) or autopsy. Occasionally, pancreatic duct anomalies can result in symptoms like abdominal pain or recurrent pancreatitis. Also, an accurate pre-operative diagnosis of ductal anomalies can prevent inadvertent duct injury during surgery. Conventionally, ERCP had been used for an accurate diagnosis of pancreatic duct anomalies. However, because it is invasive and associated with a risk of pancreatitis, it has been replaced with magnetic resonance cholangiopancreatography (MRCP). MRCP has demonstrated high sensitivity and specificity for the diagnosis of ductal anomalies, which can be further improved with the use of secretin-enhanced MRCP. Endoscopic ultrasound (EUS) is a new diagnostic and interventional tool in the armamentarium of endoscopists and has demonstrated promising results in the detection of pancreatic duct variations and anomalies. Along with the visualization of the course and configuration of the pancreatic duct, EUS can also visualize changes in the pancreatic parenchyma, thereby helping with an early diagnosis of any co-existent pancreatic disease. Absence of the stack sign and crossed duct sign are important EUS features to diagnose pancreas divisum. EUS can also help with the diagnosis of other congenital ductal anomalies like annular pancreas, ansa pancreatica, and anomalous pancreaticobiliary union, although the published experience is limited.
PubMed: 37835872
DOI: 10.3390/diagnostics13193129 -
Biomedicine & Pharmacotherapy =... Dec 2023Pancreatic cancer (PC) represents a group of malignant tumours originating from pancreatic duct epithelial cells and acinar cells, and the 5-year survival rate of PC... (Review)
Review
Pancreatic cancer (PC) represents a group of malignant tumours originating from pancreatic duct epithelial cells and acinar cells, and the 5-year survival rate of PC patients is only approximately 12%. Molecular targeted drugs are specific drugs designed to target and block oncogenes, and they have become promising strategies for the treatment of PC. Compared to traditional chemotherapy drugs, molecular targeted drugs have greater targeting precision, and they have significant therapeutic effects and minimal side effects. This article reviews several molecular targeted drugs that are currently in the experimental stage for the treatment of PC; these include antibody-drug conjugates (ADCs), aptamer-drug conjugates (ApDCs) and peptide-drug conjugates (PDCs). ADCs can specifically recognize cell surface antigens and reduce systemic exposure and toxicity of chemotherapy drugs. By delivering nucleic acid drugs to target cells, the targeting RNA of ApDCs can inhibit the expression or translation of mutated genes, thereby inhibiting tumour development. Moreover, PDCs can effectively penetrate tumour cells, and the peptide groups in PDCs preferentially target tumour cells with minimal side effects. In the targeted therapy of PC, molecular targeted drugs have very broad prospects, which provides new hope for the clinical treatment of PC patients and is worth further research.
Topics: Humans; Pancreatic Neoplasms; Immunoconjugates; Peptides; Antineoplastic Agents
PubMed: 37862965
DOI: 10.1016/j.biopha.2023.115717 -
Acta Medica Portuguesa Oct 2023Pancreatic duct adenocarcinoma is currently the sixth-leading cause of cancer death worldwide and the fourth in Europe, with a continuous increase in annual lethality in... (Review)
Review
Pancreatic duct adenocarcinoma is currently the sixth-leading cause of cancer death worldwide and the fourth in Europe, with a continuous increase in annual lethality in Portugal during the last two decades. Surgical en-bloc resection of the tumor with microscopic-negative margins and an adequate lymphadenectomy is the only possibility of long-term survival. As this type of cancer is a systemic disease, there is a high rate of recurrence even after curative resection, turning systemic therapy the core of its management, mostly based on chemotherapy. Neoadjuvant strategies for nonmetastatic disease showed significant improvement in overall survival compared with upfront surgery, namely in borderline resectable disease. Moreover, these strategies provided downstaging in several situations allowing R0 resections. Under these new oncologic strategies, several recent surgical issues were introduced, namely more aggressive vascular resections and even tumor resections in oligometastatic disease. This review revisits the state-of-the-art of surgical and oncological interventions in pancreatic duct adenocarcinoma and highlights recent advances in the field aiming to achieve higher survival rates.
Topics: Humans; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Neoadjuvant Therapy; Europe
PubMed: 37788655
DOI: 10.20344/amp.19957 -
The Korean Journal of Gastroenterology... Oct 2023The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary... (Review)
Review
The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary ampullary adenocarcinoma is a rare malignancy, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. Jaundice from a biliary obstruction is the most common symptom of ampullary adenocarcinoma. In the early stages, radical pancreatoduodenectomy is the standard surgical approach. On the other hand, no randomized controlled trial has provided evidence to guide physicians on the choice of adjuvant/palliative chemotherapy because of the rarity of the disease and the paucity of related research. This paper reports the biology, histology, current therapeutic strategies, and potential future therapies of ampullary adenocarcinoma.
Topics: Humans; Ampulla of Vater; Adenocarcinoma; Pancreatic Neoplasms; Common Bile Duct Neoplasms; Duodenal Neoplasms
PubMed: 37876255
DOI: 10.4166/kjg.2023.110