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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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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Global acetylome profiling indicates EPA impedes but OA promotes prostate cancer motility through altered acetylation of PFN1 and FLNA

PROTEOMICS, Journal Year: 2024, Volume and Issue: 24(19)

Published: March 2, 2024

Abstract Prostate cancer (PCa) is one of the leading causes morbidity and mortality in men. Metastasis main cause PCa‐associated death. Recent evidence indicated a significant reduction PCa associated with higher ω‐3 polyunsaturated fatty acids (PUFAs) consumption. However, underlying mechanisms remained elusive. In this study, we applied global acetylome profiling to study effect treatment. Results that oleic acid (OA, monounsaturated acid, MUFA, 100 µM) elevates while EPA (eicosapentaenoic reduces acetyl‐CoA level, which alters acetylome. After treatment, two crucial cell motility regulators, PFN1 FLNA, were found altered acetylation levels. OA increased whereas decreased level. Furthermore, promotes inhibits migration invasion. Immunofluorescence assay impedes formation lamellipodia or filopodia through reduced localization FLNA edge cells. Therefore, perturbed may be critical step acid‐affected motility. This provides some new insights into response PUFAs treatment better understanding invasion modulation.

Language: Английский

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Targeting Cleavage of C-Terminal Fragment of Cytoskeletal Filamin A in Cancers

Cells, Journal Year: 2024, Volume and Issue: 13(16), P. 1394 - 1394

Published: Aug. 21, 2024

Human cancers express altered levels of actin-binding cytoskeletal filamin A (FLNA) protein. FLNA in mammals consists an domain at its N-terminus that is followed by 24 immunoglobulin-like repeat modules interrupted two hinge regions between repeats 15–16 and 23–24. Cleavage these produces a naturally occurring C-terminal 90 kDa fragment (FLNACT) physically interacts with multiple proteins diverse functions. This cleavage leads to actin cytoskeleton remodeling, which turn contributes cellular signaling, nucleocytoplasmic shuttling transcriptional factors nuclear receptors, regulation their activities are important for initiation progression cancers. Therefore, recent studies have proposed blocking as means cancer therapy. Here, we update how has been targeted different approaches potential implications future treatment human

Language: Английский

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HSPB8-BAG3 chaperone complex modulates cell invasion in intrahepatic cholangiocarcinoma by regulating CASA-mediated Filamin A degradation

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: Aug. 31, 2024

The incidence of intrahepatic cholangiocarcinoma (ICC) is steadily rising, and it associated with a high mortality rate. Clinical samples were collected to detect the expression HSPB8 BAG3 in ICC tissues. cells cultured transfected plasmids that overexpressed or silenced specific genes investigate impact gene alterations on cell function. qPCR Western blot techniques utilized measure protein levels. A wound healing assay was conducted assess migration ability. Transwell used invasion Co-IP verify binding relationship between BAG3. effects lung metastasis tumors vivo verified by constructing metastatic tumor model. Through above experiments, we discovered expressions up-regulated tissues cells, their positively correlated. ability could be promoted inhibited upregulating downregulating Furthermore, HSPB8-BAG3 chaperone complex resulted abnormal degradation Filamin activating autophagy. Increased inhibits cells. Overexpression promotes regulating CASA-mediated A, offering insights for enhancing therapeutic strategies.

Language: Английский

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