Burden and risk factors of suspected cholangiocarcinoma in high Opisthorchis viverrini endemic rural communities in southern Lao PDR DOI Creative Commons
Anousin Homsana,

Phonesavanh Southisavath,

Kerstin Kling

et al.

PLoS neglected tropical diseases, Journal Year: 2024, Volume and Issue: 18(11), P. e0012617 - e0012617

Published: Nov. 27, 2024

Introduction Cholangiocarcinoma (CCA) is a major contributor to hepatobiliary mortality in the Lao People’s Democratic Republic (Lao PDR). Infection with carcinogenic trematode Opisthorchis viverrini (OV), acquired through consumption of insufficiently-cooked river fish, known risk factor for development CCA. Together OV, other factors contribute pathogenesis We conducted this study identify burden CCA and high-risk communities PDR. Method A cross-sectional was performed Champasack Savannakhet provinces, southern PDR, where OV infection highly endemic. assessed morbidity abdominal ultrasound (US). In addition, multiple or suspected be associated were such as (examined by Kato-Katz technique stool examination), lifestyle risks (e.g. smoking alcohol face-to-face questionnaire), co-morbidity diabetes mellitus) hepatitis B status, both serologically tested. Results 3,400 participants, overall prevalence 7.2% (95% confidence interval [95% CI] 5.4−9.6). The increased age, higher men at all ages. Almost participants (88.3%) infected OV. multivariate regression analysis, positively (adjusted odds ratio [aOR] 3.4, 95% CI 1.7−6.5), history cholecystectomy (aOR 2.7, 1.5−4.9). Conclusion Our screening high rural areas PDR uncovers public health burden, primarily driven elevated rates. Urgent interventions are needed curb these communities. Age gender disparities highlight need targeted efforts. Beyond notable like offer valuable insights preventive strategies. This research enhances our understanding informs initiatives

Language: Английский

The interplay of signaling pathways with miRNAs in cholangiocarcinoma pathogenicity and targeted therapy DOI
Mohamed Bakr Zaki, Ahmed I. Abulsoud, Shereen Saeid Elshaer

et al.

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 245, P. 154437 - 154437

Published: April 5, 2023

Language: Английский

Citations

48
Organoids and spheroids: advanced in vitro models for liver cancer research DOI Creative Commons
Mirella Pastore,

A. Giachi,

Elena Spínola-Lasso

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 9, 2025

Liver cancer is a leading cause of cancer-related deaths worldwide, highlighting the need for innovative approaches to understand its complex biology and develop effective treatments. While traditional in vivo animal models have played vital role liver research, ethical concerns demand more human-relevant systems driven development advanced vitro models. Spheroids organoids emerged as powerful tools due their ability replicate tumor microenvironment facilitate preclinical drug development. are simpler 3D culture that partially recreate structure cell interactions. They can be used penetration studies high-throughput screening. Organoids derived from stem cells or patient tissues accurately emulate complexity functionality tissue. generated pluripotent adult cells, well specimens, providing personalized studying behavior responses. retain genetic variability original offer robust platform screening treatment strategies. However, both spheroids limitations, such absence functional vasculature immune components, which essential growth therapeutic The field modeling evolving, with ongoing efforts predictive reflect complexities human cancer. By integrating these tools, researchers gain deeper insights into accelerate novel

Language: Английский

Citations

1
Syngeneic murine models with distinct immune microenvironments represent subsets of human intrahepatic cholangiocarcinoma DOI Creative Commons
Jennifer L. Tomlinson, Binbin Li, Jingchun Yang

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 80(6), P. 892 - 903

Published: March 7, 2024

•Transposase-mediated transduction of Fbxw7ΔF and Akt into the biliary epithelium promotes CCA carcinogenesis.•Murine cells derived from Fbxw7ΔF/Akt tumors can be implanted orthotopically mouse livers to generate a syngeneic model (FAC).•This recapitulates critical phenotypic pathological elements human iCCA.•Syngeneic murine models with different genetic drivers correspond subsets CCA.•Syngeneic iCCA display genotype-immune microenvironment phenotype correlation differential responses immunotherapy. Background & AimsCholangiocarcinoma (CCA) is poorly immunogenic malignancy associated limited survival. Syngeneic immunocompetent are an essential tool elucidate tumor immune (TIME), understand mechanisms evasion, test novel immunotherapeutic strategies. The scope this study was develop characterize distinct drivers, correlate genomics, immunobiology, therapeutic response.MethodsA multifaceted approach including scRNA-seq, CITE-seq, whole exome bulk RNA sequencing employed. FDA-approved PD-1/PD-L1 antibodies were tested in humanized mice (HuPD-H1).ResultsA intrahepatic (iCCA) driven by intrabiliary that mimics generated. From tumors, cell line (FAC) characteristics developed. Established SB1 (YAPS127A/Akt) KPPC (KrasG12Dp53L/L) compared FAC model. Although had transcriptomic similarities, they substantial differences as well. Mutation patterns FAC, SB1, matched mutational signatures Western Japanese patient cohorts. high mutation burden. T cell-infiltrated TIME, while preponderance suppressive myeloid cells. Moreover, tumor-bearing HuPD-H1 displayed nivolumab or durvalumab.ConclusionsSyngeneic between genotype TIME phenotype, immunotherapies. This underscores importance leveraging multiple preclinical immunotherapy CCA.Impact implicationsUnderstanding relationship unmet need cholangiocarcinoma (CCA). Herein, we use demonstrate models, which information will help guide other studies. Additionally, it emphasizes checkpoint inhibition patients not "one-size-fits-all" approach. Our observations suggest that, for targeted therapies, should stratified selected treatment according their genetics. Cholangiocarcinoma response. A (HuPD-H1). durvalumab. CCA.

Language: Английский

Citations

6
Cholangiocarcinoma-on-a-chip: A human 3D platform for personalised medicine DOI Creative Commons
Michela Anna Polidoro, Erika Ferrari, Cristiana Soldani

et al.

JHEP Reports, Journal Year: 2023, Volume and Issue: 6(1), P. 100910 - 100910

Published: Sept. 15, 2023

Cholangiocarcinoma (CCA) is a primary liver tumour characterised by poor prognosis and limited therapeutic options. Available 3D human CCA models fail to faithfully recapitulate the niche. We aimed develop an innovative patient-specific CCA-on-chip platform.A microenvironment was recapitulated on microfluidic three-channel chip using cells, cancer-associated fibroblasts (CAFs), endothelial T cells isolated from specimens (n = 6). CAF were co-cultured in central channel, flanked one lateral recreating tubular structure. An extensive characterisation of this platform carried out investigate its diffusion ability, hydrogel properties, changes matrix composition. Cell phenotype functional properties assessed.Primary seeded device shown reproduce architectural structure maintain original properties. The niche underwent deep remodelling device, with increase stiffness extracellular deposition, mimicking vivo characteristics. incorporated into assess reliability for immune cell interaction studies. Higher migration observed patients highly infiltrated tumours. Finally, drug trial showed ability different responses based patient characteristics.We presented that integrates major non-immune components infiltrate, reflecting This represents reliable will be help further elucidate biological mechanisms involved provide efficient tool personalised testing.An cholangiocarcinoma (CCA)-on-chip successfully developed, integrating (tumour fibroblasts, infiltrate) powerful unravelling disease-associated cellular provides testing.

Language: Английский

Citations

12
The utilisation of biliary organoids for biomedical applications DOI Creative Commons

Zhongwen Lei,

Yijun Yang, Yang Xiang

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 7, 2025

Biliary duct injury, biliary atresia (BA), tract tumors, primary sclerosing cholangitis (PSC), and other diseases are commonly encountered in clinical practice within the digestive system. To gain a better understanding of pathogenesis development these explore more effective treatment methods, organoid technology has recently garnered significant attention. Organoids three-dimensional structures derived from stem/progenitor cells that can faithfully mimic intricate structure physiological function tissues or organs vitro. They provide valuable platform for studying offer novel possibilities repairing regenerating injuries. The main seed used to construct organoids include human epithelial as well pluripotent stem cells. construction involves various techniques such traditional embedding technology, rotary culture hanging drop along with emerging approaches like organ chip (3D) printing four-dimensional (4D) technology. This article comprehensively reviews methods while discussing their applications disease modeling research on mechanisms drug screening tissue/organ repair; it also highlights current challenges suggests future directions regarding which will serve references treating common refractory system practice.

Language: Английский

Citations

0
The importance of preclinical models for cholangiocarcinoma drug discovery DOI
Florian Primavesi, Felix J. Krendl, Rupert Oberhuber

et al.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Biliary tract cancer (BTC) comprises a clinically diverse and genetically heterogeneous group of tumors along the intra- extrahepatic biliary system (intrahepatic cholangiocarcinoma) gallbladder with common feature poor prognosis, despite increasing molecular knowledge associated genetic aberrations possible targeted therapies. Therefore, search for even more precise individualized therapies is ongoing preclinical tumor models are central to development such new approaches. The described in current review include simple advanced vitro vivo models, including cell lines, 2D monolayer, spheroid organoid cultures, 3D bioprinting, patient-derived xenografts, recently, machine-perfusion platform-based resected liver specimens. All these have individual advantages, disadvantages limitations that need be considered depending on desired application. In addition potential cost limitations, availability BTC types, time required model establishment growth success rate, differently reflect relevant characteristics as heterogeneity, spatial tumor-stroma microenvironment interactions, metabolic nutritional gradients immunological interactions. consequent combination different may improve clinical study outcomes by strengthening data basis.

Language: Английский

Citations

0
Molecular subtypes of intrahepatic cholangiocarcinoma DOI Creative Commons
A. De Santis, Lei Zhu, Jianxin Tao

et al.

Trends in Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Intrahepatic cholangiocarcinoma (iCCA) presents in two clinically distinct subtypes: large duct (LD-iCCA) and small (SD-iCCA). These subtypes exhibit significant molecular, genetic, histopathological differences that impact patient prognosis treatment responsiveness. This review advocates for a subtype-specific approach to iCCA research clinical management, including tailored therapeutic strategies consider genetic profiles tumor microenvironments. Current approaches hold promise, yet efficacy varies by subtype. Additionally, molecular diagnostics, DNA methylation-based classifiers transcriptomic sequencing, have shown potential refining subclassification, thereby guiding precision medicine efforts. article outlines existing trials, key trajectories, future directions developing more effective subtype-adapted therapies iCCA.

Language: Английский

Citations

0
A drug-eluting balloon catheter coated with chitosan and paclitaxel-loaded poloxamer-stabilized PLA microparticles for the effective treatment of cholangiocarcinoma DOI

Jin Sil Lee,

Jaehee Jang,

Hyeryeon Oh

et al.

Journal of Industrial and Engineering Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Long noncoding HOXD-AS1: a crucial regulator of malignancy DOI Creative Commons

Xiang-Yuan Tao,

Qianqian Li, Shanshan Dong

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 26, 2025

Long non-coding RNAs (lncRNAs) play a crucial role in the occurrence and progression of various cancers. HOXD-AS1, an antisense RNA 1 lncRNA HOXD cluster, (also known as HAGLR, MIR7704HG, Mdgt, STEEL), is located at human chromosome 2q31.1. Recent studies have demonstrated that abnormal expression HOXD-AS1 significantly correlated with clinicopathological features patients tumors. The tumors, affecting tumor cell proliferation, apoptosis, metastasis, invasion, metabolism, drug resistance. important for cancer diagnosis prognosis evaluation. Detecting its level helps judge predict patient survival. It therapeutic target biomarker early prognosis, good clinical application prospects. This article reviews role, molecular mechanisms, potential value malignant development.

Language: Английский

Citations

0
Impact of Aberrant β-Catenin Pathway on Cholangiocarcinoma Heterogeneity DOI Creative Commons
Elisa Lozano, Paula Sanchon-Sanchez, Ana Morente-Carrasco

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(8), P. 1141 - 1141

Published: April 12, 2023

The poor prognosis of most cases advanced cholangiocarcinoma (CCA) constitutes a severe problem in modern oncology, which is aggravated by the fact that incidence this liver cancer increasing worldwide and often diagnosed late, when surgical removal not feasible. difficulty dealing with deadly tumor augmented heterogeneity CCA subtypes complexity mechanisms involved enhanced proliferation, apoptosis avoidance, chemoresistance, invasiveness, metastasis characterize CCA. Among regulatory processes implicated developing these malignant traits, Wnt/β-catenin pathway plays pivotal role. Alteration β-catenin expression subcellular localization has been associated worse outcomes some subtypes. This heterogeneity, also affects cellular vivo models commonly used to study biology anticancer drug development, must be taken into account for investigation more accurately extrapolate basic laboratory research clinical situation. A better understanding altered relationship heterogeneous forms mandatory novel diagnostic tools therapeutic strategies patients suffering from lethal disease.

Language: Английский

Citations

9