Tumor-derived exosomes: unravelling the pathogenesis of pancreatic cancer with liver metastases and exploring the potential for clinical translation.

Pancreatic cancer (PC) is one of the most malignant solid cancers, and PC metastasis, particularly liver metastasis, is a major cause of cancer mortality. A key event in tumor metastasis is the formation of pre-metastatic niche (PMN), which provides a microenvironment conducive to tumor cells colonization and progression. Various molecules loaded in tumor-derived exosomes (TDEs) contribute to PMN formation and distant tumor metastasis, by regulating immune and stromal cell function, inducing angiogenesis, and promoting metabolic reprogramming.

Cancer associated fibroblasts and metabolic reprogramming: unraveling the intricate crosstalk in tumor evolution.

Metabolic reprogramming provides tumors with an energy source and biofuel to support their survival in the malignant microenvironment. Extensive research into the intrinsic oncogenic mechanisms of the tumor microenvironment (TME) has established that cancer-associated fibroblast (CAFs) and metabolic reprogramming regulates tumor progression through numerous biological activities, including tumor immunosuppression, chronic inflammation, and ecological niche remodeling. Specifically, immunosuppressive TME formation is promoted and mediators released via CAFs and multiple immune cells that collectively support chronic inflammation, thereby inducing pre-metastatic ecological niche formation, and ultimately driving a vicious cycle of tumor proliferation and metastasis.

SIRT7 knockdown promotes gemcitabine sensitivity of pancreatic cancer cell via upregulation of GLUT3 expression.

Gemcitabine serves as a first-line chemotherapeutic treatment for pancreatic cancer (PC), but it is prone to rapid drug resistance. Increasing the sensitivity of PC to gemcitabine has long been a focus of research. Fasting interventions may augment the effects of chemotherapy and present new options.

Stem cell-like circulating tumor cells identified by Pep@MNP and their clinical significance in pancreatic cancer metastasis.

Objective: The circulating tumor cells (CTCs) could be captured by the peptide functionalized magnetic nanoparticles (Pep@MNP) detection system in pancreatic ductal adenocarcinoma (PDAC). CTCs and the CXCR4 expression were detected to explore their clinical significance. The CXCR4+ CTCs, this is highly metastatic-prone stem cell-like subsets of CTCs (HM-CTCs), were found to be associated with the early recurrence and metastasis of PDAC.

HDAC Inhibition Sensitize Hepatocellular Carcinoma to Lenvatinib via Suppressing AKT Activation.

Hepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options. As a first-line treatment for advanced HCC, Lenvatinib has been applicated in clinic since 2018. Resistance to Lenvatinib, however, has severely restricted the clinical benefits of this drug.

Hypoxia-induced epigenetic regulation of miR-485-3p promotes stemness and chemoresistance in pancreatic ductal adenocarcinoma via SLC7A11-mediated ferroptosis.

The mechanism of hypoxia in chemoresistance of pancreatic ductal adenocarcinoma (PDAC) remains elusive. In this study, we revealed the essential role of miR-485-3p in PDAC, particularly its impact on cancer stemness and gemcitabine resistance under hypoxic conditions. We found substantial downregulation of miR-485-3p in PDAC tissues, with lower expression correlating to poor patient outcomes.

Translational PET Imaging of Nectin-4 Expression in Multiple Different Cancers with Ga-N188.

Nectin cell adhesion molecule 4 (nectin-4) is a transmembrane protein overexpressed on a variety of cancers and plays an important role in oncogenic and metastatic processes. The nectin-4-targeted antibody-drug conjugate enfortumab vedotin has been approved for treating locally advanced or metastatic urothelial cancer, but the efficacy in other types of cancer remains to be explored. The aim of this study was to evaluate the feasibility of nectin-4-targeted PET imaging with Ga-N188 as a noninvasive method to quantify membranous nectin-4 expression in multiple tumor types-an approach that may provide insight for patient stratification and treatment selection.

Pharmacogenomic profiling of intra-tumor heterogeneity using a large organoid biobank of liver cancer.

Inter- and intra-tumor heterogeneity is a major hurdle in primary liver cancer (PLC) precision therapy. Here, we establish a PLC biobank, consisting of 399 tumor organoids derived from 144 patients, which recapitulates histopathology and genomic landscape of parental tumors, and is reliable for drug sensitivity screening, as evidenced by both in vivo models and patient response. Integrative analysis dissects PLC heterogeneity, regarding genomic/transcriptomic characteristics and sensitivity to seven clinically relevant drugs, as well as clinical associations.

Disruption of Super-Enhancers in Activated Pancreatic Stellate Cells Facilitates Chemotherapy and Immunotherapy in Pancreatic Cancer.

One major obstacle in the drug treatment of pancreatic ductal adenocarcinoma (PDAC) is its highly fibrotic tumor microenvironment, which is replete with activated pancreatic stellate cells (a-PSCs). These a-PSCs generate abundant extracellular matrix and secrete various cytokines to form biophysical and biochemical barriers, impeding drug access to tumor tissues. Therefore, it is imperative to develop a strategy for reversing PSC activation and thereby removing the barriers to facilitate PDAC drug treatment.

Feasibility of novel intraoperative navigation for anatomical liver resection using real-time virtual sonography combined with indocyanine green fluorescent imaging technology.

To analyze the feasibility and clinical effect of novel intraoperative navigation of real-time virtual sonography (RVS) combined with indocyanine green (ICG) fluorescent imaging technology in anatomical liver resection (ALR) for hepatocellular carcinoma. The clinical data of 41 patients who underwent ALR using RVS intraoperative navigation combined with ICG fluorescent imaging technology in the Department of Hepatobiliary Surgery of Peking University International Hospital from January 2020 to May 2022 were retrospectively analyzed. RVS was applied to guide the surgical plane through fusing real-time intraoperative ultrasound images with corresponding preoperative CT or MRI images.

Single-cell transcriptome profiling of primary tumors and paired organoids of pancreatobiliary cancer.

Single-cell RNA-seq (scRNA-seq) and cancer organoid model have shown promise in investigating tumor microenvironment heterogeneity and facilitating chemotherapeutic drug testing to inform treatment selection. It is still unknown whether the scRNA-seq results based on organoid can faithfully reflect the heterogeneity of primary pancreatobiliary cancer. To reveal the similarities and differences between primary tumors and their matched organoids at transcriptome level, we conducted scRNA-seq for paired primary tumors and organoids from one cholangiocarcinoma (CCA) and two pancreatic ductal adenocarcinoma (PDAC) patients.

Single-cell RNA-seq reveals characteristics in tumor microenvironment of PDAC with MSI-H following neoadjuvant chemotherapy with anti-PD-1 therapy.

Accumulating evidence suggests the minority of patients with advanced pancreatic ductal adenocarcinoma (PDAC) that have microsatellite instability high (MSI-H) can benefit from immune checkpoint inhibitors (ICIs). However, the effects of ICIs on the tumor microenvironment (TME) of PDAC remain elusive. We conducted single-cell RNA-seq (scRNA-seq) analysis on a residual lesion from a MSI-H PDAC patient who received a radical operation after eight cycles of neoadjuvant treatment (nab-paclitaxel/gemcitabine plus pembrolizumab).

Clinical characteristics of liver injury induced by immune checkpoint inhibitors in patients with advanced biliary tract carcinoma.

Immune-related liver injuries are closely associated with the liver's fundamental state. Patients with advanced biliary tract carcinoma (BTC) have poor liver function. We evaluated the clinical data of immune-related liver injury in patients with advanced BTC and gastric cancer (GC) during immune checkpoint inhibitor (ICI) treatment between February 2019 and July 2022 at Peking University First Hospital.

The benefits of neoadjuvant therapy for patients with resectable pancreatic cancer: an updated systematic review and meta-analysis.

Neoadjuvant therapy (NAT) was effective in improving overall survival (OS) of borderline resectable pancreatic cancer. However, its application in resectable pancreatic cancer remains controversial. This study aimed to determine whether NAT has a greater advantage over conventional upfront surgery (US) in terms of resection rate, R0 resection rate, positive lymph node rate, and OS.

Cross-species scRNA-seq reveals the cellular landscape of retina and early alterations in type 2 diabetes mice.

Single-cell RNA sequencing (scRNA-seq) analysis have provided an unprecedented resolution for the studies on diabetic retinopathy (DR). However, the early changes in the retina in diabetes remain unclear. A total of 8 human and mouse scRNA-seq datasets, containing 276,402 cells were analyzed individually to comprehensively delineate the retinal cell atlas.

Efficacy and safety of early drain removal following pancreatic resections: a meta-analysis.

Background: No consensus was reached with regard to the effect of EDR on postoperative outcomes after pancreatic surgery. The meta-analysis was designed to explore the efficacy and safety of early drain removal (EDR).

Methods: Systematic literature search was performed.

Exosomal miR-485-3p derived from pancreatic ductal epithelial cells inhibits pancreatic cancer metastasis through targeting PAK1.

Background: Cell competition is an important feature in pancreatic cancer (PC) progression, but the underlying mechanism remains elusive. This study aims to explore the role of exosomes derived from normal pancreatic ductal epithelial cells involved in PC progression.

Methods: PC cells and pancreatic stellate cells (PSCs) were treated with exosomes isolated from pancreatic ductal epithelial cells.

Single-cell RNA-seq transcriptomic landscape of human and mouse islets and pathological alterations of diabetes.

Single-cell RNA sequencing has paved the way for delineating the pancreatic islet cell atlas and identifying hallmarks of diabetes. However, pathological alterations of type 2 diabetes (T2D) remain unclear. We isolated pancreatic islets from control and T2D mice for single-cell RNA sequencing (scRNA-seq) and retrieved multiple datasets from the open databases.

Single Cell RNA-Seq Identifies Immune-Related Prognostic Model and Key Signature-SPP1 in Pancreatic Ductal Adenocarcinoma.

There are no reliable biomarkers for early diagnosis or prognosis evaluation in pancreatic ductal adenocarcinoma (PDAC). Multiple scRNA-seq datasets for PDAC were retrieved from online databases and combined with scRNA-seq results from our previous study. The malignant ductal cells were identified through calculating copy number variation (CNV) scores.

Safety evaluation of early drain removal following pancreaticoduodenectomy: A single-center retrospective cohort study.

Objectives: The effects of early drain removal (EDR) on postoperative complications after pancreaticoduodenectomy (PD) remains to be investigated. This single-center retrospective cohort study was designed to explore the safety of EDR after PD.

Methods: A total of 112 patients undergoing PD with drain fluid amylase (DFA) on postoperative day (POD) 1 and 3 <= 5000 were divided into EDR and late drain removal (LDR).

The effect of minimally invasive or open radical antegrade modular pancreatosplenectomy on pancreatic cancer: A multicenter randomized clinical trial protocol.

Background: Radical antegrade modular pancreatosplenectomy (RAMPS) has been proven to improve R0 resection and lymph harvest in treating patients with distal pancreatic cancer. The development of minimally invasive surgery has advantages in postoperative recovery. Therefore, minimally invasive (MI-) RAMPS may combine the advantages of both benefits to improve survival.

Crosstalk between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts in the Tumor Microenvironment Mediated by Exosomal MicroRNAs.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant digestive tumors, characterized by a low rate of early diagnosis, strong invasiveness, and early metastasis. The abundant stromal cells, dense extracellular matrix, and lack of blood supply in PDAC limit the penetration of chemotherapeutic drugs, resulting in poor efficacy of the current treatment regimens. Cancer-associated fibroblasts (CAFs) are the major stromal cells in the tumor microenvironment.