• Biliary tract cancer
• Biomarkers
• Cell free DNA
• Cholangiocarcinoma
• Circulating RNA
• Circulating tumour DNA
• Circulating tumour cells
• Extracellular vesicles
• Precision medicine

• Humans
• Liquid Biopsy/methods
• Cholangiocarcinoma/diagnosis
• Cholangiocarcinoma/pathology
• Cholangiocarcinoma/blood
• Cholangiocarcinoma/therapy
• Bile Duct Neoplasms/diagnosis
• Bile Duct Neoplasms/pathology
• Bile Duct Neoplasms/blood
• Bile Duct Neoplasms/genetics
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/genetics
• Prognosis
• Neoplastic Cells, Circulating/pathology
• Circulating Tumor DNA/blood
• Circulating Tumor DNA/genetics
• Circulating Tumor DNA/analysis
• Extracellular Vesicles/metabolism
• Early Detection of Cancer/methods
• Precision Medicine/methods

• Cholangiocarcinoma/diagnosis
• Cholangiocarcinoma/pathology
• Humans
• Biomarkers, Tumor/metabolism
• Bile Duct Neoplasms/diagnosis
• Bile Duct Neoplasms/pathology
• Prognosis
• Risk Factors

• U01 CA283935 NCI NIH HHS
• U01 CA288375 NCI NIH HHS
• R01 CA255621 NCI NIH HHS
• R01 CA282178 NCI NIH HHS
• R01 CA233794 NCI NIH HHS

• central nervous system
• high-frequency sampling
• human in vivo
• non-invasive
• urinary astrocyte-derived extracellular vesicles

• Extracellular Vesicles/metabolism
• Astrocytes/metabolism
• Humans
• Ultracentrifugation
• Microscopy, Electron, Transmission
• Nerve Growth Factors/urine
• Nerve Growth Factors/metabolism

• Enfermedades hepáticas
• Investigación traslacional
• Liver disease
• Translational research

• Humans
• Biomarkers
• Gastroenterology
• Liver
• Liver Diseases/diagnosis
• Spain
• Translational Research, Biomedical

• Primary Sclerosing Cholangitis
• RNA-binding proteins
• bioinformatics
• biomarkers
• cholangiocarcinoma
• data mining
• extracellular vesicles

• biomarker
• cholangiocarcinoma
• circular RNA
• diagnosis
• long non-coding RNA
• non-coding RNA
• prognosis

• Cholangiocarcinoma/genetics
• Cholangiocarcinoma/diagnosis
• Humans
• Biomarkers, Tumor/genetics
• Prognosis
• Bile Duct Neoplasms/genetics
• Bile Duct Neoplasms/diagnosis
• RNA, Long Noncoding/genetics
• Gene Expression Regulation, Neoplastic
• RNA, Untranslated/genetics
• MicroRNAs/genetics
• RNA, Circular/genetics

• biomarker
• cholangiocarcinoma
• exosome
• extracellular vesicles
• liquid biopsy
• microparticle

• Diagnostic
• PLA2G12B
• PLA2G2A
• Prognostic biomarkers cholangiocarcinoma

• biomarkers
• chronic liver diseases
• diagnosis
• extracellular vesicles
• non-coding RNAs

• Humans
• RNA, Long Noncoding/genetics
• Carcinoma, Hepatocellular/genetics
• Liver Neoplasms/genetics
• RNA, Untranslated/physiology
• MicroRNAs/genetics
• Biomarkers/metabolism
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/genetics
• Liver Cirrhosis/pathology
• Extracellular Vesicles/metabolism
• Fatty Liver/pathology

• ISP23-101 Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia

• Exosomes
• biomarker
• cancer
• diagnosis
• therapeutics

• EV-based therapy
• cholangiocarcinoma
• exosome
• extracellular vesicles
• tumor microenvironment

• biomarkers
• cholangiocarcinoma
• drug delivery
• exosomes
• extracellular vesicles
• microvesicles
• therapy

• Humans
• Cholangiocarcinoma/diagnosis
• Cholangiocarcinoma/therapy
• Cholangiocarcinoma/etiology
• Extracellular Vesicles
• Cell Communication
• Bile Ducts, Intrahepatic
• Bile Duct Neoplasms/diagnosis
• Bile Duct Neoplasms/therapy
• Bile Duct Neoplasms/etiology

• Humans
• Liquid Biopsy
• Cell-Free Nucleic Acids/genetics
• Biomarkers
• Neoplastic Cells, Circulating/pathology
• Extracellular Vesicles

• P01 CA069246 NCI NIH HHS
• R01 CA229777 NCI NIH HHS
• U01 CA230697 NCI NIH HHS
• U01 CA233360 NCI NIH HHS
• R01 CA237500 NCI NIH HHS
• R01 CA239078 NCI NIH HHS
• U01 CA233370 NCI NIH HHS

• biomarkers
• cholangiocarcinoma
• diagnosis
• pathogenesis
• primary sclerosing cholangitis
• surveillance

• Humans
• Extracellular Vesicles/metabolism
• Extracellular Vesicles/pathology
• Non-alcoholic Fatty Liver Disease/metabolism
• Models, Biological
• Biological Transport

• R01 DK130884 NIDDK NIH HHS
• R01 DK111378 NIDDK NIH HHS
• P30 DK084567 NIDDK NIH HHS
• U01 AA021788 NIAAA NIH HHS
• R01 DK122948 NIDDK NIH HHS

• biomarkers
• body fluids
• exosomes
• extracellular vesicles
• methodology
• plasma
• tumors

• 08071219 Italian Ministry of Health, Ricerca Corrente
• LINEA 2 "Dotazione annuale per attività istituzionale" University of Milan, Italy, Piano di Sostegno alla Ricerca 2020

• bile
• biomarker
• cholangiocarcinoma
• extracellular vesicle
• phosphatidylcholine

• Advanced Research Facilities & Services, Hamamatsu University School of Medicine
• 655006 HUSM Grant-in-Aid
• JP20gm0910004 AMED
• 21ak0101179 AMED
• 19H03728 JSPS KAKENHI
• 19K09167 JSPS KAKENHI
• JP22H02793 JSPS KAKENHI

• angiogenesis
• cancer
• circRNA
• extracellular vesicles
• ischemic strokes
• lncRNA
• microRNA

• Humans
• Ischemic Stroke
• Proteomics
• Neoplasms/drug therapy
• RNA, Untranslated/genetics
• Extracellular Vesicles

• cancer
• biomarkers
• gastroenterology

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary hepatic malignancy worldwide. However, currently available systemic therapies are of limited effectiveness, and the median overall survival of patients treated with first-line standard chemotherapy is less than one year. Immune checkpoint inhibitors have been used to treat solid tumors. Clinical studies recently explored the combination of chemotherapy and immunotherapy for CCA. However, the clinical significance of predictive biomarkers for chemo-immunotherapy in CCA remains unclear. It is also worth exploring whether a combination of chemotherapeutic agents can increase the sensitivity of CCA immunotherapy.

This study reports a case of advanced iCCA in which clinical complete remission had been achieved using a programmed death 1 (PD-1) inhibitor and paclitaxel without known predictive biomarkers, but with BRCA1, KRAS, and NTRK3 mutations after rapid progression to first-line chemotherapy, and has remained in clinical complete remission for more than two years. This case suggests that chemo-immunotherapy is a potential therapeutic option for patients with iCCA and few known predictive biomarkers for immunotherapies as well as synergistic effect of the combination of paclitaxel and PD-1 monoclonal antibody.

The combination of paclitaxel and PD-1 monoclonal antibodyr can be explored in patients with advanced iCCA.

• Intrahepatic cholangiocarcinoma
• Programmed cell death protein-1 inhibitor
• Paclitaxel
• Chemo-immunotherapy
• Predictive biomarker
• Case report

• Biomarker
• Cholangiocarcinoma
• Diagnostics

To quantitatively analyze lipid molecules in tumors and adjacent tissues of intrahepatic cholangiocarcinoma (ICC), to establish diagnostic model and to examine lipid changes with clinical classification.

We measured the quantity of 202 lipid molecules in 100 tumor observation points and 100 adjacent observation points of patients who were diagnosed with ICC. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were handles, along with Student’s t-test to identify specific metabolites. Prediction accuracy was validated in the validation set. Another logistic regression model was also established on the training set and validated on the validation set.

Distinct separation was obtained from PCA and OPLS-DA model. Ten differentiating metabolites were identified using PCA, OPLA-DA and Lasso regression: [m/z 722.5130], [m/z 863.5655], [m/z 436.2834], [m/z 474.2626], [m/z 661.4813], [m/z 750.5443], [m/z 571.2889], [m/z 836.5420], [m/z 772.5862] and [m/z 478.2939]. Using logical regression, a diagnostic equation: y = 3.4*[m/z 436.2834] - 3.773*[m/z 474.2626] + 3.82*[m/z 661.4813] - 4.394*[m/z 863.5655] + 10.165 based on four metabolites successfully differentiated cancerous areas from adjacent normal areas. The AUROC of the model reached 0.993 (95% CI: 0.985–0.999) in the validation group. Compared with the adjacent non-tumor area, three characteristic metabolites FA (22:4), PA (P-18:0/0:0) and Glucosylceramide (d18:1/12:0) showed an increasing trend from stage I to stage II, while seven other metabolites LPA(16:0), PE(34:2), PE(36:4), PE(38:3), PE(40:6), PE(40:5) and LPE(16:0) showed a decreasing trend from stage I to stage II.

We successfully identified lipid molecules in differentiating tumor tissue and adjacent tissue of ICC, established a discrimination logistic model which could be used as a classifier to classify tumor and non-tumor regions based on analysis in tumor margins and provided information for biomarker changes in ICC, and proposed to related lipid changes with clinical classification.

• Early diagnosis
• Extracellular vesicle
• Hepatobiliary tumor
• Liquid biopsy
• Pancreatic tumor

• CHOLANGIOCARCINOMA
• HEPATOBILIARY CANCER
• TUMOUR MARKERS

• bile cytology
• bile duct biopsy
• cell block
• endoscopic retrograde cholangiography
• immunohistochemistry
• malignant biliary strictures

We aim to develop a signature that could accurately predict prognosis and evaluate the response to immune checkpoint blockade (ICB) in bladder urothelial carcinoma (BLCA).

Based on comprehensive analysis of public database, we identified prognosis-related hub genes and investigated their predictive values for the ICB response in BLCA.

Among 69 common DEGs, three genes (AURKA, BIRC5, and CKS1B) were associated with poor prognosis, and which were related to histological subtypes, TP53 mutation status, and the C2 (IFN-gamma dominant) subtype. Three genes and their related risk model can effectively predict the response of immunotherapy. Their related drugs were identified through analysis of drug bank database.

Three genes could predict prognosis and evaluate the response to ICB in BLCA.

• Cholangiocarcinoma (CCA)
• FGFR2 fusion
• IDH
• targeted therapies
• tumor biomarkers

Surgery is the only curative treatment for cholangiocarcinoma. However, most patients present with advanced disease, and hence are unresectable. Thus, the intent of treatment shifts from curative to palliative in the majority of cases. Biliary drainage with intraluminal brachytherapy is an effective means of relieving the malignant biliary obstruction. In this review, we discuss the role of brachytherapy in the palliation of obstructive symptoms in extrahepatic cholangiocarcinoma.

• Biliary tract
• Cholangiocarcinoma
• Extrahepatic
• Intraluminal brachytherapy

Cholangiocarcinoma (CCA) refers to an aggressive malignancy with a high fatality rate and poor prognosis. Globally, the morbidity of CCA is increasing for the past few decades, which has progressed into a disease that gravely endangers human health. Exosomes belong to a class of extracellular vesicles (EVs) with diameters ranging from 40 to 150 nm that can be discharged by all living cells. As communication messengers of the intercellular network, exosomes carry a diverse range of cargoes such as proteins, nucleic acids, lipids, and metabolic substances, which are capable of conveying biological information across different cell types to mediate various physiological activities or pathological changes. Increasing studies have demonstrated that exosomes in the tumor microenvironment participate in regulating tumorigenesis and progression via multiple approaches in the tumor microenvironment. Here, we reviewed the current research progress of exosomes in the context of cancer and particularly highlighted their functions in modulating the development of CCA. Furthermore, the potential values of exosomes as diagnostic and therapeutic targets in CCA were overviewed as well.

Primary sclerosing cholangitis (PSC) is an idiopathic and heterogenous cholestatic liver disease characterized by chronic inflammation and fibrosis of the biliary tree. Currently, no effective therapies are available for this condition, whose incidence is rising. At present, specificity and sensitivity of current serum markers used to diagnose PSC are limited and often unreliable. In this study, we characterize circulating extracellular vesicles and provide supporting data on their potential use as novel surrogate biomarkers for PSC. EVs are membrane surrounded structures, 100–1000 nm in size, released by cells under various conditions and which carry a variety of bioactive molecules, including small non-coding RNAs, lipids and proteins. In recent years, a large body of evidence has pointed to diagnostic implications of EVs and relative cargo in various human diseases. We isolated EVs from serum of well-characterized patients with PSC or control subjects by differential centrifugation and size-exclusion chromatography. A complete characterization identified elevated levels of circulating EVs in PSC patients compared to healthy control subjects (2000 vs. 500 Calcein-FITC + EVs/μL). Tissue and cell specificity of circulating EVs was assessed by identification of liver-specific markers and cholangiocyte marker CK-19. Further molecular characterization identified 282 proteins that were differentially regulated in PSC-derived compared to healthy control-EVs. Among those, IL-13Ra1 was the most significantly and differentially expressed protein in PSC-derived EVs and correlated with the degree of liver fibrosis. In addition to protein profiling, we performed a miRNA-sequencing analysis which identified 11 among established, liver-specific (e.g., miR-122 and miR-192) and novel miRNAs. One of the newly identified miRNAs, miR-4645-3p, was significantly up-regulated fourfold in PSC-derived EVs compared to circulating EVs isolated from healthy controls. This study provides supporting evidence of the potential role of circulating EVs and associated protein and miRNA cargo as surrogate noninvasive and reliable biomarker for PSC.

Pharmacogenomics (PGx) entails the study of heritability of drug response. This may include both variability in genes related to pharmacokinetics (drug absorption, distribution, metabolism and excretion) and pharmacodynamics (e.g., drug receptors or signaling pathways). Individualizing drug therapy taking into account the genetic profile of the patient has the potential to make drug therapy safer and more effective. Currently, this approach relies on the determination of genetic variants in pharmacogenes by genotyping. However, it is widely acknowledged that large variability in gene expression is attributed to non-structural genetic variants. Therefore, at least from a theoretical viewpoint individualizing drug therapy based upon expression of pharmacogenes rather than on genotype may be advantageous but has been difficult to implement in the clinical setting. Extracellular vesicles (EVs) are lipid encapsulated structures that contain cargo such as lipids, nucleic acids and proteins. Since their cargo is tissue- and cell-specific they can be used to determine the expression of pharmacogenes in the liver. In this review, we describe methods of EV isolation and the potential of EVs isolated from liquid biopsies as a tool to determine the expression of pharmacogenes for use in personalized medicine.

• cancer
• digestive system
• fusion gene
• targeted therapy