Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.712
Filtrar
1.
Sci Data ; 10(1): 33, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653372

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm, and its incidence has doubled over the past two decades owing to increasing risk factors. Despite surveillance, most HCC cases are diagnosed at advanced stages and can only be treated using transarterial chemo-embolization (TACE) or systemic therapy. TACE failure may occur with incidence reaching up to 60% of cases, leaving patients with a financial and emotional burden. Radiomics has emerged as a new tool capable of predicting tumor response to TACE from pre-procedural computed tomography (CT) studies. This data report defines the HCC-TACE data collection of confirmed HCC patients who underwent TACE and have pre- and post-procedure CT imaging studies and available treatment outcomes (time-to-progression and overall survival). Clinically curated segmentation of pre-procedural CT studies was done for the purpose of algorithm training for prediction and automatic liver tumor segmentation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Resultado do Tratamento
2.
World J Gastroenterol ; 29(3): 413-424, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36688022

RESUMO

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies, recurrence rates remain high. In contrast to first-line treatment for HCC, which relies on several factors, including clinical staging, tumor burden, and liver function, there is no consensus or general treatment recommendations for recurrent HCC (R-HCC). Locoregional therapies include a spectrum of minimally invasive liver-directed treatments which can be used as either curative or neoadjuvant therapy for HCC. Herein, we provide a comprehensive review of recent evidence using salvage loco-regional therapies for R-HCC after failed curative-intent.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Terapia Neoadjuvante
3.
World J Gastroenterol ; 29(1): 43-60, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36683711

RESUMO

Given the frequent co-existence of an aggressive tumor and underlying chronic liver disease, the management of hepatocellular carcinoma (HCC) patients requires experienced multidisciplinary team discussion. Moreover, imaging plays a key role in the diagnosis, staging, restaging, and surveillance of HCC. Currently, imaging assessment of HCC entails the assessment of qualitative characteristics which are prone to inter-reader variability. Radiomics is an emerging field that extracts high-dimensional mineable quantitative features that cannot be assessed visually with the naked eye from medical imaging. The main potential applications of radiomic models in HCC are to predict histology, response to treatment, genetic signature, recurrence, and survival. Despite the encouraging results to date, there are challenges and limitations that need to be overcome before radiomics implementation in clinical practice. The purpose of this article is to review the main concepts and challenges pertaining to radiomics, and to review recent studies and potential applications of radiomics in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Diagnóstico por Imagem , Estudos Retrospectivos
4.
Can J Vet Res ; 87(1): 74-81, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36606034

RESUMO

The objective of this study was to evaluate unidimensional (mm), bidimensional (mm2), or tridimensional (mL) computed tomography (CT) tumor measurements for ability to discriminate changes in lesion size and predict survival in dogs with nonresectable hepatic carcinoma treated with drug-eluting bead transarterial-chemoembolization (DEB-TACE) and to compare CT response via Response Evaluation Criteria in Solid Tumors 1.1 (mm), World Health Organization (mm2), ellipsoid and spherical volume (mL), and percent necrosis, for their ability to differentiate treatment responders. This was a prospective, single-arm clinical trial. DEB-TACE was performed to varying levels of blood flow stasis in 16 client-owned dogs with nonresectable hepatic carcinoma. Computed tomography imaging responses were assessed and compared to median survival time. Results revealed that initial, follow-up, or changes in unidimensional, bidimensional, or tridimensional tumor measurements were not associated with survival. Larger bidimensional and tridimensional tumor measurements/body weight on initial and follow-up CT were significantly associated with a shorter median survival time [bidimensional (P = 0.04, 0.016) and tridimensional (P = 0.025, 0.015), respectively]. A higher percent necrosis on initial CT was significantly associated with a shorter median survival time (P = 0.038). Ellipsoid volumetric criteria detected treatment response most frequently; however, response classification was not associated with median survival time. Computed tomography bidimensional and tridimensional tumor measurements/body weight before and after DEB-TACE may help to predict median survival time for dogs undergoing DEB-TACE for hepatic carcinoma.


L'objectif de cette étude était d'évaluer les mesures tumorales unidimensionnelles (mm), bidimensionnelles (mm2) ou tridimensionnelles (mL) par tomodensitométrie (CT) pour déterminer la capacité de discriminer les changements de taille des lésions et de prédire la survie chez les chiens atteints d'un carcinome hépatique non-résécable traité avec un médicament par chimioembolisation transartérielle par billes à élution (DEB-TACE) et pour comparer la réponse CT via les critères d'évaluation de la réponse dans les tumeurs solides 1,1 (mm), l'Organisation mondiale de la santé (mm2), le volume ellipsoïde et sphérique (mL) et le pourcentage de nécrose, pour leur capacité à différencier les répondeurs au traitement. Il s'agissait d'un essai clinique prospectif à un seul volet. Le DEB-TACE a été réalisé à différents niveaux de stase du flux sanguin chez 16 chiens appartenant à des clients atteints d'un carcinome hépatique non-résécable. Les réponses d'imagerie par tomodensitométrie ont été évaluées et comparées au temps de survie médian. Les résultats ont révélé que les mesures initiales, de suivi ou les modifications des mesures tumorales unidimensionnelles, bidimensionnelles ou tridimensionnelles n'étaient pas associées à la survie. Des mesures tumorales bidimensionnelles et tridimensionnelles plus grandes/poids corporel sur la CT initiale et de suivi étaient significativement associées à un temps de survie médian plus court [bidimensionnel (P = 0,04, 0,016) et tridimensionnel (P = 0,025, 0,015), respectivement]. Un pourcentage plus élevé de nécrose au scanner initial CT était significativement associé à une durée de survie médiane plus courte (P = 0,038). Les critères volumétriques ellipsoïdes ont détecté la réponse au traitement le plus fréquemment; cependant, la classification des réponses n'était pas associée à la durée médiane de survie. La tomodensitométrie bidimensionnelle et tridimensionnelle des mesures tumorales/poids corporel avant et après DEB-TACE peut aider à prédire la durée médiane de survie des chiens subissant DEB-TACE pour un carcinome hépatique.(Traduit par Docteur Serge Messier).


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Doenças do Cão , Neoplasias Hepáticas , Animais , Cães , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/veterinária , Quimioembolização Terapêutica/veterinária , Quimioembolização Terapêutica/métodos , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/veterinária , Necrose/terapia , Necrose/veterinária , Estudos Prospectivos , Tomografia Computadorizada por Raios X/veterinária , Resultado do Tratamento
5.
Sci Rep ; 13(1): 335, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611046

RESUMO

The TBC1 domain family member 10B (EPI64B/TBC1D10B), a member of the RabGAP EPI64 subfamily, contains a TBC domain that confers GTPase-activating protein activity. Even though overexpression of TBC1D10B has been reported to promote tumor invasion and metastasis in gastric adenocarcinoma, the prognostic value of TBC1D10B and its correlation with DNA methylation and immune infiltration in hepatocellular carcinoma are still not known. Transcriptional expression profiles of TBC1D10B between hepatocellular carcinoma tissues and normal tissues were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus. The Clinical Proteomic Tumor Analysis Consortium and the Human Protein Atlas were used to assess the TBC1D10B protein expression. The biological functions of TBC1D10B were evaluated by the Metascape database and by Gene Set Enrichment Analysis (GSEA). Receiver operating characteristic (ROC) curve analysis was used to distinguish hepatocellular carcinoma from adjacent normal tissues. The effect of TBC1D10B on survival was estimated using the Kaplan-Meier method. DNA methylation in the TBC1D10B gene was assessed using the online MEXPRESS and MethSurv tools. The association between TBC1D10B mRNA expression and immune cell infiltration was investigated by the TIMER2 web server, tumor immune estimation resource and single-sample GSEA. This study found that TBC1D10B is highly expressed in hepatocellular carcinoma and that increased TBC1D10B mRNA expression is associated with female sex, lower Body Mass Index, high level of alpha fetal protein, and worse clinical stages. The mRNA and protein levels of TBC1D10B were verified in cells. Functional annotation indicated enrichment with negative regulation of the cell cycle, extracellular matrix, and corresponding pathways in the high-TBC1D10B phenotype. The ROC curve analysis showed that, with a cutoff level of 2.912, the accuracy, sensitive, and specificity in differentiate TBC1D10B hepatocellular carcinoma from adjacent controls were 0.931, 0.920, and 0.802, respectively. Kaplan-Meier survival analysis showed that hepatocellular carcinoma patients with high TBC1D10B had a worse prognosis than those with low TBC1D10B, especially in patients with a weight below 70 kg, height above 170 cm, and histological G2 and G3. We also found that the methylation of TBC1D10B was associated with the prognosis in patients with hepatocellular carcinoma. Moreover, correlation analysis indicated that TBC1D10B mRNA expression was positively correlated with infiltration levels of most immune cells, but negatively correlated with Th17 and cytotoxic cells infiltration. Our study indicates that increased TBC1D10B expression in hepatocellular carcinoma may play a role in tumorigenesis by regulating the cell cycle and extracellular matrix. TBC1D10B may be a novel prognostic and predictive marker and immune therapeutic target in hepatocellular carcinoma patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Feminino , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Prognóstico , Proteômica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Biomarcadores , Imunoterapia , Biomarcadores Tumorais/genética , Proteínas Adaptadoras de Transdução de Sinal
6.
Cells ; 12(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36611994

RESUMO

BACKGROUND: Immune interactions play important roles in the regulation of T cells' cytotoxic function, further impacting the anti-tumor efficacy of immunotherapy. A comprehensive analysis of immune cell types in HCC and immune-cell-related signatures predicting prognosis and monitoring immunotherapy efficacy is still absent. METHODS: More than 1,300 hepatocellular carcinomas (HCC) patients were collected from public databases and included in the present study. The ssGSEA algorithm was applied to calculate the infiltration level of 28 immunocyte subpopulations. A cell pair algorithm was applied to construct an immune-cell-related prognostic index (ICRPI). Survival analyses were performed to measure the survival difference across ICRPI risk groups. Spearman's correlation analyses were used for the relevance assessment. A Wilcoxon test was used to measure the expression level's differences. RESULTS: In this study, 28 immune subpopulations were retrieved, and 374 immune cell pairs (ICPs) were established, 38 of which were picked out by the least absolute shrinkage and selection operator (LASSO) algorithm. By using the selected ICPs, the ICRPI was constructed and validated to play crucial roles in survival stratification and dynamic monitoring of immunotherapy effect. We also explored several candidate drugs targeting ICRPI. A composite ICRPI and clinical prognostic index (ICPI) was then constructed, which achieved a more accurate estimation of HCC's survival and is a better choice for prognosis predictions in HCC. CONCLUSIONS: In conclusion, we constructed and validated ICRPI based on the cell pair algorithm in this study, which might provide some novel insights for increasing the survival estimation and clinical response to immune therapy for individual HCC patients and contribute to the personalized precision immunotherapy strategy of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Imunoterapia , Algoritmos , Bases de Dados Factuais
7.
Sci Rep ; 13(1): 1137, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670201

RESUMO

Aging is an inevitable consequence of life, characterized by a progressive decline in tissue and organ function and an increased risk of death. There is growing evidence that aging is closely related to tumor development and immune regulation. However, in hepatocellular carcinoma, the relationship between cellular senescence and immune infiltration, energy metabolism, chemokines, and immunotherapeutic response is unclear and needs further study. We first analyzed 274 cellular senescence-associated genes by the NMF algorithm and identified two cellular senescence-associated clusters. Subsequently, we compared the differences between the two clusters, in terms of immune infiltration, energy metabolism, chemokines, and immunotherapeutic response to treatment. We further constructed risk models using cellular senescence-associated signature genes that could effectively identify the two subpopulations. Finally, we validated the validity and robustness of the risk model using an external dataset. We found significant differences in survival prognosis between two cellular senescence-associated clusters. In addition, we found significant differences in immune cell infiltration, expression of energy metabolism-related genes, expression of chemokine-related genes, expression of immune checkpoint-related genes, Tumor Immune Dysfunction and Exclusion between the two clusters. Also, a scoring system associated with cellular senescence was developed and validated as an independent prognostic indicator. It was validated as an independent prognostic factor and immunotherapeutic predictor for HCC. It was validated as an independent prognostic factor and immunotherapeutic predictor for HCC. The cellular senescence-related scoring system was validated as an independent prognostic factor and immunotherapy predictor for HCC, and patients with low CSS were characterized by prolonged survival time. Our study confirmed the relationship between cellular senescence and immune cell infiltration, energy metabolism, chemokines, expression of immune checkpoint-related genes, and response to immunotherapy. This enhances our understanding of cellular senescence and tumor immune microenvironment, energy metabolism, chemokines, and provides new insights to improve immunotherapy outcomes in HCC patients. It provides new insights to improve the outcome of immunotherapy in HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Senescência Celular , Imunoterapia , Metabolismo Energético , Microambiente Tumoral , Prognóstico
8.
Sci Rep ; 13(1): 533, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631548

RESUMO

We aimed to identify hepatocellular carcinoma (HCC) patients who will respond to repetitive transarterial chemoembolization (TACE) to improve the treatment algorithm. Retrospectively, 61 patients (mean age, 65.3 years ± 10.0 [SD]; 49 men) with 94 HCC mRECIST target-lesions who had three consecutive TACE between 01/2012 and 01/2020 were included. Robust and non-redundant radiomics features were extracted from the 24 h post-embolization CT. Five different clinical TACE-scores were assessed. Seven different feature selection methods and machine learning models were used. Radiomics, clinical and combined models were built to predict response to TACE on a lesion-wise and patient-wise level as well as its impact on overall-survival prognostication. 29 target-lesions of 19 patients were evaluated in the test set. Response rates were 37.9% (11/29) on the lesion-level and 42.1% (8/19) on the patient-level. Radiomics top lesion-wise response prognostications was AUC 0.55-0.67. Clinical scores revealed top AUCs of 0.65-0.69. The best working model combined the radiomic feature LargeDependenceHighGrayLevelEmphasis and the clinical score mHAP_II_score_group with AUC = 0.70, accuracy = 0.72. We transferred this model on a patient-level to achieve AUC = 0.62, CI = 0.41-0.83. The two radiomics-clinical features revealed overall-survival prognostication of C-index = 0.67. In conclusion, a random forest model using the radiomic feature LargeDependenceHighGrayLevelEmphasis and the clinical mHAP-II-score-group seems promising for TACE response prognostication.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Masculino , Humanos , Idoso , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Estudos Retrospectivos , Quimioembolização Terapêutica/métodos , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos
9.
BMC Gastroenterol ; 23(1): 11, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631744

RESUMO

OBJECTIVE: Transcatheter arterial chemoembolization (TACE) has been widely applied in the treatment of hepatocellular carcinoma (HCC). Our study aimed to investigate the feasibility and efficacy of transradial access as an alternative to transfemoral access for TACE. METHODS: Patients undergoing TACE were divided into the radial artery (RA) route group or the femoral artery (FA) route group according to the operation approach, namely, transradial or transfemoral access. We retrospectively analysed the clinical characteristics, technical outcomes, clinical efficacy and incidence of adverse events to compare the two technologies for intervention for HCC. RESULTS: Transradial access was found to achieve superior technical outcomes and clinical efficacy, as the patients in the RA group had a lower rate of hepatic arterial spasm, a higher partial response rate and a lower progression rate than the patients in the FA group according to the mRECIST evaluations. In contrast, the liver function indices and VAS (visual analogue scale) pain scores were consistent across the two groups. Moreover, patients in the RA group had a shorter length of stay than those in the FA group, despite similar hospitalization expenses. The total adverse events were significantly reduced by transradial access for TACE (72.5% vs. 84.1%, P = 0.027). CONCLUSION: Our study suggested that transradial access is an effective and feasible alternative to transfemoral access for TACE. Large-scale prospective randomized controlled studies are expected.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Estudos Retrospectivos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Estudos Prospectivos , Quimioembolização Terapêutica/efeitos adversos , Resultado do Tratamento
11.
J Am Coll Surg ; 236(2): 399-410, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36648268

RESUMO

BACKGROUND: Fibrolamellar hepatocellular carcinoma (FLC) is a rare malignancy that primarily affects patients in late adolescence and young adulthood. FLC tumors are characterized by their unique histologic features and a recently discovered genomic alteration, a chimeric fusion protein found in nearly all tumors. This review article provides the latest advancements in diagnosing, imaging, and managing FLC. STUDY DESIGN: A comprehensive systematic review was performed using MEDLINE/PubMed and Web of Science databases, with the end of search date being July 1, 2022, regarding FLC diagnosis, imaging, and management. RESULTS: Surgical resection remains the mainstay of therapy offering a chance for cure; however, given the incidence of metastatic disease at diagnosis and high rates of distant relapse, systemic therapies remain a crucial component of disease control. Unfortunately, few systemic therapies have demonstrated proven benefits. Consequently, recent efforts have galvanized around single-institute or small consortia-based studies specifically focused on enrolling patients with FLC or using agents with a biologic rationale. CONCLUSIONS: FLC has unique demographic, radiologic, and pathologic features. The rarity of these tumors, coupled with the only recent acknowledgment of the genomic abnormality, has likely led to disease underrecognition and deprioritization of collaborative efforts to establish an evidence-based standard of care. Despite R0 resection, most patients experience recurrence. However, surgical resection is feasible for many recurrences and is associated with good survival. The role of chemotherapy is evolving, and further research is required to define its role in managing this disease.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adolescente , Humanos , Adulto Jovem , Adulto , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia , Prognóstico
12.
Technol Cancer Res Treat ; 22: 15330338221136694, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36600679

RESUMO

Hepatocellular carcinoma is a leading cause of cancer-related death in many parts of the world. Traditional treatment options are not always effective. During the promising minimally invasive electroporation-based therapies, biological cell membranes are exposed to an external, sufficiently high, pulsed electric field which creates so-called nanopores into the lipid bilayer of the cell membrane. These pores can either be permanent (irreversible electroporation (IRE)), leading to apoptosis, or repairable (reversible electroporation (RE)), with continued cell function. In tumor therapy, RE is used to increase the diffusion of a chemotherapeutic drug during electrochemotherapy. For both IRE and RE, the success of the treatment is dependent on application of the appropriate electric field. Therefore, this study aims to define the pulse parameters and thresholds for IRE and RE on hepatocellular carcinoma (HepG2) cells in-vitro.In a custom-made in-vitro setup, HepG2 cell viability (0, 5, 10, and 15 min), and the peak temperature were measured after electroporation with the different IRE and RE pulsing protocols, to determine the most successful settings for IRE and RE. A CAM/PI flow cytometric assay was performed to confirm cell permeabilization for the RE pulsing protocols with the highest cell viability.The results indicated that an IRE pulsing protocol (70 pulses, 100 µs pulse length, and 100 ms interval) with an electric field strength of 4000 V/cm was needed as threshold for almost complete cell death of HepG2 cells. A RE pulsing protocol (8 pulses, 100 µs pulse length, and 1000 ms interval) with an electric field strength of 1000 V/cm was needed as threshold for viable and permeabilized HepG2 cells. The low peak temperatures (max 30.1°C for IRE, max 23.1°C for RE) within this study indicated that the reduction in HepG2 cell viability was caused by the applied electric field and was not a result of Joule heating.


Assuntos
Carcinoma Hepatocelular , Eletroquimioterapia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Eletroporação/métodos , Temperatura
14.
BMC Cancer ; 23(1): 57, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36647032

RESUMO

Circadian clock genes are significant in the occurrence and development of HCC and long-non coding RNAs (lncRNAs) are closely related to HCC progression. In this study, we aimed to establish a prognostic risk model for HCC. Circadian clock-related lncRNAs expressed in HCC were extracted from The Cancer Genome Atlas. A nomogram was established to predict individual survival rate. Biological processes enriched for risk model transcripts were investigated by Gene Set Enrichment Analysis. Further, we evaluated the relationship between risk score and immune-checkpoint inhibitor-related gene expression level. The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to assess the sensitivity of tumors in high- and low-risk score groups to different drugs. A total of 11 circadian clock-related lncRNAs were included in multi-Cox proportional hazards model analysis to establish a risk model. Univariate and multivariate Cox regression analysis showed that the risk model was an independent risk factor in HCC. The risk model was a significantly associated with the immune signature. Further GDSC analysis indicated that patients in each risk score group may be sensitive to different anti-cancer drugs. QRT-PCR analysis results showed that C012073.1, PRRT3-AS1, TMCC1-AS1, LINC01138, MKLN1-AS, KDM4A-AS1, AL031985.3, POLH-AS1, LINC01224, and AC099850.3 were more highly expressed in Huh-7 and HepG2, compared to LO2, while AC008549.1 were lower expressed. Our work established a prognostic model for HCC. Risk score analysis indicated that the model is significantly associated with modulation tumor immunity and could be used to guide more effective therapeutic strategies in the future.


Assuntos
Carcinoma Hepatocelular , Relógios Circadianos , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Relógios Circadianos/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Prognóstico , RNA Longo não Codificante/genética
16.
Int J Mol Sci ; 24(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36674607

RESUMO

The liver is a secondary and often collateral target of COVID-19 disease but can lead to important consequences. COVID-19 might directly cause a high number of complications in patients with pre-existing chronic liver disease, increasing their risk of hepatic decompensation. Moreover, it also determines indirect consequences in the management of patients with liver disease, especially in those suffering from decompensated cirrhosis and HCC, as well as in the execution of their follow-up and the availability of all therapeutic possibilities. Liver imaging in COVID-19 patients proved to be highly nonspecific, but it can still be useful for identifying the complications that derive from the infection. Moreover, the recent implementation of telemedicine constitutes a possible solution to both the physical distancing and the re-organizational difficulties arising from the pandemic. The present review aims to encompass the currently hypothesized pathophysiological mechanisms of liver injury in patients with COVID-19 mediated by both the direct invasion of the virus and its indirect effects and analyze the consequence of the pandemic in patients with chronic liver disease and liver tumors, with particular regard to the management strategies that have been implemented to face this worldwide emergency and that can be further improved.


Assuntos
COVID-19 , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/terapia , COVID-19/complicações , Cirrose Hepática/etiologia
17.
Cancer Biol Ther ; 24(1): 1-9, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36482717

RESUMO

Hepatocellular cancer (HCC) is a serious illness with high prevalence and mortality throughout the whole world. For advanced HCC, immunotherapy is somewhat impactful and encouraging. Nevertheless, a substantial proportion of patients with advanced HCC are still unable to achieve a durable response, owing to heterogeneity from clonal variability and differential expression of the PD-1/PD-L1 axis. Recently, heat shock factor 1 (HSF1) is recognized as an important component of tumor immunotherapeutic response as well as related to PD-L1 expression in cancer. However, the mechanism of HSF1 regulating PD-L1 in cancer, especially in HCC, is still not fully clear. In this study, we observed the significantly positive correlation between HSF1 expression and PD-L1 expression in HCC samples; meanwhile combination expressions of HSF1 and PD-L1 served as the signature for predicting prognosis of patients with HCC. Mechanistically, HSF1 upregulated PD-L1 expression by inducing APOJ expression and activating STAT3 signaling pathway in HCC. In addition, we explored further the potential values of targeting the HSF1-APOJ-STAT3 axis against CD8+ T cells-mediated cancer cells cytotoxicity. These findings unveiled the important involvement of HSF1 in regulating PD-L1 expression in HCC as well as provided a novel invention component for improving the clinical response rate and efficacy of PD-1/PD-L1 blockade.


Assuntos
Carcinoma Hepatocelular , Fatores de Transcrição de Choque Térmico , Imunoterapia , Neoplasias Hepáticas , Humanos , Antígeno B7-H1/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Linfócitos T CD8-Positivos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Receptor de Morte Celular Programada 1/genética , Fator de Transcrição STAT3/genética , Fatores de Transcrição de Choque Térmico/genética
18.
Eur J Cell Biol ; 102(1): 151284, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36584598

RESUMO

Hepatocellular carcinoma (HCC) is the most common type of primary hepatic cancer and is among the major causes of mortality due to cancer. Due to the lack of efficient conventional therapeutic options for this cancer, particularly in advanced cases, novel treatments including immunotherapy have been considered. However, despite the encouraging clinical outcomes after implementing these innovative approaches, such as oncolytic viruses (OVs), adoptive cell therapies (ACT), immune checkpoint blockades (ICBs), and cancer vaccines, several factors have restricted their therapeutic effect. The main concern is the existence of an immunosuppressive tumor microenvironment (TME). Combination of different ICBs or ICBs plus tyrosine kinase inhibitors have shown promising results in overcoming these limiting factors to some extent. Combination of programmed cell death ligand-1 (PD-L1) antibody Atezolizumab and vascular endothelial growth factor (VEGF) antibody Bevacizumab has become the standard of care in the first-line therapy for untestable HCC, approved by regulatory agencies. This paper highlighted a wide overview of the direct and indirect immunotherapeutic strategies proposed for the treatment of HCC patients and the common challenges that have hindered their further clinical applications.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Fator A de Crescimento do Endotélio Vascular , Neoplasias Hepáticas/terapia , Imunoterapia , Terapia Baseada em Transplante de Células e Tecidos , Microambiente Tumoral
19.
Mol Pharm ; 20(1): 331-340, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36490361

RESUMO

With few curative treatments and a global yearly death rate of over 800,000, hepatocellular carcinoma (HCC) desperately needs new therapies. Although wild-type p53 gene therapy has been shown to be safe in HCC patients, it has not shown enough efficacy to merit approval. This work aims to show how p53 can be re-engineered through fusion to the pro-apoptotic BH3 protein Bcl-2 antagonist of cell death (Bad) to improve anti-HCC activity and potentially lead to a novel HCC therapeutic, p53-Bad*. p53-Bad* is a fusion of p53 and Bad, with two mutations, S112A and S136A. We determined mitochondrial localization of p53-Bad* in liver cancer cell lines with varying p53 mutation statuses via fluorescence microscopy. We defined the apoptotic activity of p53-Bad* in four liver cancer cell lines using flow cytometry. To determine the effects of p53-Bad* in vivo, we generated and analyzed transgenic zebrafish expressing hepatocyte-specific p53-Bad*. p53-Bad* localized to the mitochondria regardless of the p53 mutation status and demonstrated superior apoptotic activity over WT p53 in early, middle, and late apoptosis assays. Tumor burden in zebrafish HCC was reduced by p53-Bad* as measured by the liver-to-body mass ratio and histopathology. p53-Bad* induced significant apoptosis in zebrafish HCC as measured by TUNEL staining but did not induce apoptosis in non-HCC fish. p53-Bad* can induce apoptosis in a panel of liver cancer cell lines with varying p53 mutation statuses and induce apoptosis/reduce HCC tumor burden in vivo in zebrafish. p53-Bad* warrants further investigation as a potential new HCC therapeutic.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Peixe-Zebra/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Carga Tumoral , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Terapia Genética , Linhagem Celular Tumoral
20.
Abdom Radiol (NY) ; 47(1): 115-122, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34581927

RESUMO

AIM: To determine inter-reader agreement in categorization of imaging features using the Liver Imaging Reporting and Data System (LI-RADS) treatment response (LR-TR) algorithm in patients with hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization (cTACE). METHODS: Two radiologists used the LR-TR algorithm to assess 112 computed tomography (CT) examinations of 102 patients treated with cTACE. The inter-observer agreement in categorization of LR-TR features was assessed using kappa (κ) statistics. RESULTS: There was substantial inter-observer agreement between the two reviewers using the LR-TR algorithm (κ = 0.70; 95% CI 0.58-0.81). The two reviewers categorized tumors as non-viable in 37 (33.0%) and 39 (34.8%) of 112 examinations, viable in 58 (51.8%) and 62 (55.4%) examinations, and equivocal in 18 (16.1%) and 11 (9.8%) examinations, respectively. There was almost perfect inter-observer agreement for the LR-TR non-viable category (κ = 0.80; 95% CI 0.68-0.92), substantial agreement for the viable category (κ = 0.78 95% CI 0.67-0.90), and fair agreement for the equivocal category (κ = 0.25; 95% CI 0.02-0.49). CONCLUSION: The LR-TR algorithm conveys high degrees of inter-observer agreement for the assessment of CT imaging features in the viable and non-viable categories. Further refinement of indeterminate features may be necessary to improve the correct categorization of equivocal lesions.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Algoritmos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Meios de Contraste , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética/métodos , Variações Dependentes do Observador , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...