Unveiling the prognostic role of blood inflammatory indexes in a retrospective cohort of patients undergoing liver resection for intrahepatic cholangiocarcinoma

International Journal of Surgery, Journal Year: 2024, Volume and Issue: 110(11), P. 7088 - 7096

Published: July 5, 2024

Systemic inflammation is relevant in intrahepatic cholangiocarcinoma (iCCA), but controversial results exist on the prognostic role of inflammatory indexes and their correlation with tumor microenvironment. The authors aimed to explore biological values these indexes. A retrospective cohort study involving iCCA patients who underwent hepatic resection between 2010 2021 was conducted. neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte (LMR), clinic-pathological factors were recorded. Immune-cell subpopulations, isolated from surgical specimens, analyzed by flow cytometry. NLR LMR cut-offs calculated X-Tile software. Linear regression, Kaplan-Meier, Cox regression analyses total 101 considered. ≥3.83 <2.28 correlated worse survival. Patients divided into groups: 67 (66.3%) low-risk 34 (33.7%) high-risk (having at least one ratio). 5-year overall survival 49.8 18.9% for low- groups, respectively ( P =0.003). An elevated CA19-9 group gives 2.148 HR (95% CI: 1.060-4.349) mortality 2.182 1.206-3.948) disease recurrence. Flow cytometry analysis 20 specimens highlighted that associated tumor-derived =0.026) tumor-infiltrating lymphocytes =0.002). In a subset five vs patients, T-cell evaluation showed higher prevalence CD4+ compared CD8+ cells (78.5 vs. 21.5%, <0.0001). Conversely, demonstrated noteworthy infiltration (21.5 48.7%, =0.037). combination blood determined two survival-risk profiles. scores microenvironment suggests link immune-cell risk group. These findings open possibility patient stratification chance identify subgroups suitable dedicated follow-up targeted immuno-chemotherapy protocols.

Language: Английский

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The importance of preclinical models for cholangiocarcinoma drug discovery

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

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Management of intrahepatic cholangiocarcinoma: a review for clinicians

Gastroenterology report, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 1, 2025

Abstract Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy that arises from second-order biliary epithelial cells. Its incidence gradually increasing worldwide. Well-known risk factors have been described, although in many cases, they are not identifiable. Treatment options continuously expanding, but the prognosis of iCCA remains dismal. R0 resection only curative treatment, a limited number patients can benefit it. Frequently, major hepatectomies needed to completely remove tumour. This could contraindicate surgery or increase postoperative morbidity with chronic disease and small remnant volume. In cases anticipated inadequate future remnant, regenerative techniques may be used expand resectability. The role extent lymphadenectomy still matters debate. Improvements diagnosis better understanding genetic profiles might lead optimized surgical approaches drug therapies. neoadjuvant adjuvant therapies broadening, gaining more acceptance clinical practice. Combining locoregional novel drugs, such as checkpoint-inhibitors molecular-targeted molecules, improve treatment survival rates. Liver transplantation, after very poor initial results, now receiving attention for unresectable early (i.e. &lt;2 cm) cirrhotic livers, showing outcomes comparable those hepatocellular carcinoma. Ongoing prospective protocols testing efficacy transplantation unresectable, advanced tumours confined liver, sustained response treatment. changing landscape, aim our work review state-of-the-art medical iCCA.

Language: Английский

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Precision medicine and personalized treatment

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 151 - 174

Published: Jan. 1, 2025

Language: Английский

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Preclinical Models of Hepatocellular Carcinoma: Current Utility, Limitations, and Challenges

Biomedicines, Journal Year: 2024, Volume and Issue: 12(7), P. 1624 - 1624

Published: July 22, 2024

Hepatocellular carcinoma (HCC), the predominant primary liver tumor, remains one of most lethal cancers worldwide, despite advances in therapy recent years. In addition to traditional chemically and dietary-induced HCC models, a broad spectrum novel preclinical tools have been generated following advent transgenic, transposon, organoid, silico technologies overcome this gloomy scenario. These models become rapidly robust instruments unravel molecular pathogenesis cancer establish new therapeutic approaches against deadly disease. The present review article aims summarize discuss commonly used for HCC, evaluating their strengths weaknesses.

Language: Английский

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A method to generate perfusable physiologic-like vascular channels within a liver-on-chip model

Biomicrofluidics, Journal Year: 2023, Volume and Issue: 17(6)

Published: Dec. 1, 2023

The human vasculature is essential in organs and tissues for the transport of nutrients, metabolic waste products, maintenance homeostasis. integration vessels vitro organs-on-chip may, therefore, improve similarity to native organ microenvironment, ensuring proper physiological functions reducing gap between experimental research clinical outcomes. This particularly evident drug testing use vascularized models may provide more realistic insights into responses drugs pre-clinical phases development pipeline. In this context, different liver have been developed recapitulate architecture hepatic sinusoid, exploiting either porous membranes or bioprinting techniques. work, we a method generate perfusable vascular channels with circular cross section within without any interposing material parenchyma surrounding environment. Through technique, sinusoid-on-chip systems inclusion space Disse were designed developed. recapitulation layer, hepatocytes endothelial cells physiologically present milieu, seems enhance functionality (e.g., albumin production) compared when are close contact cells. These findings pave way numerous further uses microfluidic technologies coupled tissue immune system perfusion) as well multiorgan-on-chip settings.

Language: Английский

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Filamin A is involved in human intrahepatic cholangiocarcinoma aggressiveness and progression

Liver International, Journal Year: 2023, Volume and Issue: 44(2), P. 518 - 531

Published: Nov. 27, 2023

Abstract Background & Aims Intrahepatic cholangiocarcinoma (iCCA) is a primary liver tumour, characterized by poor prognosis and lack of effective therapy. The cytoskeleton protein Filamin A (FLNA) involved in cancer progression metastasis, including cancer. FLNA cleaved calpain, producing 90 kDa fragment (FLNA CT ) that can translocate to the nucleus inhibit gene transcription. We herein aim define role its cleavage iCCA carcinogenesis. Methods Results evaluated expression localization samples from patients ( n = 82) revealing was independently correlated with disease‐free survival. Primary tumour cells isolated resected expressed both , bulk RNA sequencing revealed significant enrichment cell proliferation motility pathways iCCAs high expression. Further, we defined impact on migration 3) HuCCT1 line using silencing Calpeptin, calpain inhibitor. observed decreased Calpeptin able reduce p < .05 vs. control). Moreover, 100 μM <.00001 control) Conclusions These findings demonstrate human calpeptin strongly expression, reducing migration.

Language: Английский

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Cellular Senescence in Liver Cancer: How Dying Cells Become “Zombie” Enemies

Biomedicines, Journal Year: 2023, Volume and Issue: 12(1), P. 26 - 26

Published: Dec. 21, 2023

Liver cancer represents the fourth leading cause of cancer-associated death worldwide. The heterogeneity its tumor microenvironment (TME) is a major contributing factor metastasis, relapse, and drug resistance. Regrettably, late diagnosis makes most liver patients ineligible for surgery, frequent failure non-surgical therapeutic options orientates clinical research to investigation new drugs. In this context, cellular senescence has been recently shown play pivotal role in progression chronic inflammatory diseases, ultimately cancer. Moreover, stem-like state triggered by associated with emergence drug-resistant, aggressive clones. recent years, an increasing number studies have emerged investigate senescence-associated hepatocarcinogenesis derived therapies, promising results. review, we intend provide overview evidence that unveils forms primary metastatic cancer, focusing on involvement mechanism therapy

Language: Английский

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Computational and experimental advances in liver-on-a-chip technology for cancer research: a systematic review

Biophysical Reviews, Journal Year: 2024, Volume and Issue: 17(1), P. 151 - 167

Published: Dec. 14, 2024

The integration of numerical simulations with Liver-on-a-Chip (LoC) technology offers an innovative approach for studying liver physiology and pathology, especially in the context cancer. Numerical facilitate optimization microfluidic devices' design deepen understanding fluid flow mass transfer. However, despite significant advancements, challenges such as replicating full complexity microenvironment scaling up high-throughput screening persist. This systematic review explores current advancements LoC devices, a particular emphasis on their combined use experimental studies cancer research. A comprehensive search across multiple databases, including ScienceDirect, Wiley Online Library, Scopus, Springer Link, Web Science, PubMed, was conducted to gather relevant literature. Our findings indicate that combination both techniques this field is still rare, resulting final selection 13 original research papers. underscores importance continued interdisciplinary refine these technologies enhance application personalized medicine therapy. By consolidating existing studies, aims highlight key identify challenges, propose future directions rapidly evolving field.

Language: Английский

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Recapitulating the Cancer‐Immunity Cycle on a Chip

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

The cancer-immunity cycle is a fundamental framework for understanding how the immune system interacts with cancer cells, balancing T cell recognition and elimination of tumors while avoiding autoimmune reactions. Despite advancements in immunotherapy, there remains critical need to dissect each phase cycle, particularly interactions among tumor, vasculature, within tumor microenvironment (TME). Innovative platforms such as organ-on-a-chip, organoids, bioprinting microphysiological systems (MPS) are increasingly utilized enhance these interactions. These meticulously replicate crucial aspects TME responses, providing robust study progression, evasion, therapeutic interventions greater physiological relevance. This review explores latest MPS technologies modeling various stages cancer-immune critically evaluating their applications limitations advancing dynamics guiding development next-generation immunotherapeutic strategies.

Language: Английский

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