Alpha-fetoprotein: Past, present, and future

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(5)

Published: April 12, 2024

Alpha-fetoprotein (AFP) is a glycoprotein that plays an important role in immune regulation with critical involvement early human development and maintaining the balance during pregnancy. Postfetal development, regulatory mechanisms controlling AFP undergo shift gene transcription suppressed. Instead, these enhancers refocus their activity to maintain albumin throughout adulthood. During postnatal period, expression can increase setting of hepatocyte injury, regeneration, malignant transformation. It first oncoprotein discovered routinely used as part screening strategy for HCC. has been shown be powerful prognostic biomarker, multiple HCC prognosis models confirmed independent utility AFP. also useful predictive biomarker monitoring treatment response In addition its roles modulation promote tumorigenesis thus investigated therapeutic target this review article, we aim provide overview AFP, encompassing discovery, biological role, combination other biomarkers how it impacts clinical practice future direction.

Language: Английский

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Role of the AKT signaling pathway in regulating tumor-associated macrophage polarization and in the tumor microenvironment: A review

Medicine, Journal Year: 2025, Volume and Issue: 104(5), P. e41379 - e41379

Published: Jan. 31, 2025

Tumor-associated macrophages (TAMs) are present in and important components of the tumor microenvironment (TME). TAMs differentiate into 2 functionally distinct morphologies, classically activated (M1)-type alternatively (M2)-type TAMs, when stimulated by different cytokines. The types exhibit properties functions. M1 secrete high levels pro-inflammatory chemotactic factors, exerting proinflammatory, antitumor effects. Conversely, M2 alter extracellular matrix, facilitate cellular immune escape, stimulate angiogenesis, thereby promoting anti-inflammatory responses growth. ratio to TME is closely related prognosis tumor. Tumor cells other can regulate polarization thus promote progression through secretion various substances; however, polarized also act on exosomes, forming a positive feedback loop. Therefore, modulating phenotype or blocking might be new approach for cancer treatment. However, intracellular signaling pathways involved poorly understood. AKT pathway an polarization, growth, proliferation, recruitment, apoptosis as well action within TME. This paper reviews regulation provides ideas immunotherapy.

Language: Английский

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Prognosis prediction of α-FAtE score for locoregional immunotherapy in hepatocellular carcinoma

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

The α-FAtE score, composed of alpha-fetoprotein, alkaline phosphatase, and eosinophil levels, has been reported as a predictor prognosis in hepatocellular carcinoma (HCC) patients treated with atezolizumab plus bevacizumab. This study aimed to investigate the predictive ability score for efficacy safety locoregional immunotherapy treatment HCC patients. We conducted retrospective 446 at Sun Yat-sen University Cancer Center from January 1st 2019 2023. performance was evaluated by concordance index, area under receiver operating characteristics curve, Kaplan-Meier curve multiple Cox regression analysis. were divided into 0-1 group (n=211) 2-3 (n=235). median progression-free survival(PFS) 7.3 months (95%CI 6.6-8.7 months), 12.3 (95% CI 10.4-14.1 months; P<0.001), respectively. overall survival (OS) 16.3 13.7-21.5 months) 34.1 27.6-NA had higher complete response (CR) rate experienced less drug-related adverse events than those group. Moreover, lower identified an independent prognostic indicator both OS PFS advanced receiving immunotherapy. is superior immunotherapy, offering valuable tool patient stratification planning.

Language: Английский

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Based on disulfidptosis-related glycolytic genes to construct a signature for predicting prognosis and immune infiltration analysis of hepatocellular carcinoma

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 23, 2023

Hepatocellular carcinoma (HCC) comprises several distinct molecular subtypes with varying prognostic implications. However, a comprehensive analysis of signature for HCC based on related to disulfidptosis and glycolysis, as well associated metabolomics the immune microenvironment, is yet be fully explored.Based differences in expression disulfide-related glycolytic genes (DRGGs), patients were divided into different by consensus clustering. Establish verify risk prognosis signature. Finally, level key gene SLCO1B1 was evaluated using immunohistochemistry (IHC) quantitative real-time PCR (qRT-PCR) HCC. The association between this cells explored multiplex immunofluorescence. biological functions cell counting kit-8, wound healing, colony formation assays studied.Different have specific clinicopathological features, microenvironment. We identified seven valuable constructed risk-prognosis Analysis score revealed that compared high-risk group, low-risk group had better prognosis, higher scores, more abundant immune-related pathways, consistent tumor subtypes. Furthermore, IHC qRT-PCR analyses showed decreased tissues. Functional experiments overexpression inhibited proliferation, migration, invasion cells.We developed can assist clinicians predicting overall survival provides reference value targeted therapy.

Language: Английский

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Exploring the potential of treating chronic liver disease targeting the PI3K/Akt pathway and polarization mechanism of macrophages

Heliyon, Journal Year: 2023, Volume and Issue: 9(6), P. e17116 - e17116

Published: June 1, 2023

Chronic liver disease is a significant public health issue that can lead to considerable morbidity and mortality, imposing an enormous burden on healthcare resources. Understanding the mechanisms underlying chronic pathogenesis developing effective treatment strategies are urgently needed. In this regard, activation of resident macrophages, namely Kupffer cells, plays vital role in inflammation fibrosis. Macrophages display remarkable plasticity polarize into different phenotypes according diverse microenvironmental stimuli. The polarization macrophages M1 pro-inflammatory or M2 anti-inflammatory regulated by complex signaling pathways such as PI3K/Akt pathway. This review focuses investigating potential using plant chemicals targeting pathway for treating while elucidating mechanism under microenvironments. Studies have demonstrated inhibiting M1-type macrophage promoting M2-type effectively combat diseases alcoholic disease, non-alcoholic fatty acts pivotal modulator survival, migration, proliferation, their responses metabolism inflammatory signals. Activating induces cytokine expression, resulting promotion M2-like phenotype facilitate tissue repair resolution inflammation. Conversely, could enhance M1-like phenotype, which exacerbates damage. Targeting has tremendous therapeutic strategy regulating activity treat with chemicals, providing new avenues treatment.

Language: Английский

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The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: April 10, 2024

Hepatocellular carcinoma (HCC) is a prevalent malignant cancer worldwide, characterized by high morbidity and mortality rates. Alpha-fetoprotein (AFP) glycoprotein synthesized the liver yolk sac during fetal development. However, serum levels of AFP exhibit significant correlation with onset progression HCC in adults. Extensive research has demonstrated that tumor microenvironment (TME) plays crucial role transformation HCC, key factor TME, promoting The objective this review was to analyze existing knowledge regarding TME. Specifically, focused on effect various cells immune evasion, clinical application diagnosis treatment HCC. These findings offer valuable insights into

Language: Английский

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Structural characteristics of alpha-fetoprotein, including N-glycosylation, metal ion and fatty acid binding sites

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: April 27, 2024

Abstract Alpha-fetoprotein (AFP), a serum glycoprotein, is expressed during embryonic development and the pathogenesis of liver cancer. It serves as clinical tumor marker, function carcinogen, immune suppressor, transport vehicle; but detailed AFP structural information has not yet been reported. In this study, we used single-particle cryo-electron microscopy(cryo-EM) to analyze structure recombinant obtained 3.31 Å cryo-EM built an atomic model AFP. We observed identified certain features AFP, including N-glycosylation at Asn251, four natural fatty acids bound distinct domains, coordination metal ions by residues His22, His264, His268, Asp280. Furthermore, compared similarities differences between human albumin. The elucidation AFP’s characteristics only contributes deeper understanding its functional mechanisms, also provides basis for developing AFP-based drug vehicles.

Language: Английский

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Macrophage polarization in bone implant repair: A review

Tissue and Cell, Journal Year: 2023, Volume and Issue: 82, P. 102112 - 102112

Published: May 20, 2023

Macrophages (MΦ) are highly adaptable and functionally polarized cells that play a crucial role in various physiological pathological processes. Typically, MΦ differentiate into two distinct subsets: the proinflammatory (M1) anti-inflammatory (M2) phenotypes. Due to their potent immunomodulatory properties, have garnered significant attention recent decades. In context of bone implant repair, function is paramount importance. Depending on polarization phenotype, can exert varying effects osteogenesis, angiogenesis, inflammatory response around implant. This paper provides an overview repair implants.

Language: Английский

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Identification of molecular subtypes based on PANoptosis-related genes and construction of a signature for predicting the prognosis and response to immunotherapy response in hepatocellular carcinoma

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 18, 2023

Previous studies have demonstrated that PANoptosis is strongly correlated with cancer immunity and progression. This study aimed to develop a PANoptosis-related signature (PANRS) explore its potential value in predicting the prognosis immunotherapy response of hepatocellular carcinoma (HCC).Based on expression genes, three molecular subtypes were identified. To construct signature, differentially expressed genes between different subjected multivariate least absolute shrinkage selection operator Cox regression analyses. The risk scores patients training set calculated using signature. classified into high-risk low-risk groups based median scores. predictive performance was evaluated Kaplan-Meier plotter, receiving operating characteristic curves, nomogram, calibration curve. results validated external datasets. Additionally, correlation immune landscape drug sensitivity examined. Furthermore, effect LPCAT1 knockdown HCC cell behavior verified vitro experiments.This developed PANRS. score obtained by PANRS an independent factor for exhibited good prognostic performance. nomogram constructed clinical information can accurately predicted survival probability HCC. Patients high tend generate immunosuppressive microenvironment. They also favorable immunotherapy, as evidenced tumor mutational burden, checkpoint gene expression, human leukocyte antigen low dysfunction exclusion enabled identification 15 chemotherapeutic agents, including sorafenib, levels, guiding treatment. upregulated lines. markedly decreased proliferation migration.PANRS predict consequently guide individualized

Language: Английский

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Alpha-Fetoprotein (AFP) biosensors

Clinica Chimica Acta, Journal Year: 2025, Volume and Issue: 573, P. 120293 - 120293

Published: April 10, 2025

Language: Английский

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