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1.
Braz. J. Pharm. Sci. (Online) ; 58: e18984, 2022. graf
Article in English | LILACS | ID: biblio-1364429

ABSTRACT

Interferon-ß-1a (INF-ß-1a) has gained significant attention due to its emerging applications in the treatment of different human diseases. Therefore, many researchers have attempted to produce it in large quantities and also in a biologically active form using different expression systems. In the present study, we aimed to improve the expression level of INF-ß-1a by Pichia pastoris using optimization of culture conditions. The codon-optimized INF-ß- 1a gene was cloned into pPICZαA plasmid under the control of alcohol oxidase I (AOX1) promoter. The protein expression was induced using different concentrations of methanol at different pHs and temperatures. The biological activity of produced protein was evaluated by anti-proliferative assay. The ideal culture conditions for the expression of INF-ß-1a by P. pastoris were found to be induction with 2% methanol at pH 7.0 culture medium at 30 C which yielded a concentration of 15.5 mg/L INF-ß-1a in a shake flask. Our results indicate that differences in glycosylation pattern could result in different biological activities as INF- ß-1a produced by P. pastoris could significantly more reduce the cell viability of HepG-2 cells, a hepatocellular carcinoma cell line, than a commercially available form of this protein produced by CHO


Subject(s)
Pichia/classification , Interferon-beta/agonists , Carcinoma, Hepatocellular/pathology , Process Optimization , Codon , Cells , Carcinoma, Hepatocellular , Hydrogen-Ion Concentration
2.
Rev. colomb. cir ; 37(1): 96-105, 20211217. fig, tab
Article in Spanish | LILACS | ID: biblio-1357579

ABSTRACT

Introducción. La resección quirúrgica es el tratamiento de elección de las neoplasias primarias y secundarias del hígado. Los pacientes con hepatocarcinoma de los segmentos centrales representan un reto, siendo la hepatectomía extendida la técnica más usada, sin embargo, el riesgo postquirúrgico de falla hepática es alto, dado que la resección puede comprometer entre el 65 % y el 80 % del volumen hepático. La mesohepatectomía es una alternativa que permite dejar un volumen hepático residual suficiente. El objetivo de este trabajo es presentar nuestra experiencia en el tratamiento de pacientes con hepatocarcinomas en segmentos centrales a quienes se les realizó mesohepatectomía. Serie de casos. Se presentan tres pacientes no cirróticos, con hepatocarcinoma en los segmentos 4, 5 y 8, que fueron atendidos en el Hospital San Vicente Fundación, en las sedes de Medellín y de Rionegro, entre 2018 y 2020. Resultados. La mesohepatectomía se realizó mediante ligadura selectiva de los pedículos del segmento 4 y del sector anterior derecho. Se utilizó aspirador ultrasónico y endograpadora para la transección hepática. La duración de la maniobra de Pringle varió entre 16 y 43 minutos. El sangrado promedio fue de 1000 ml. Solo un paciente presentó fuga biliar tipo B. No hubo mortalidad a 30 días. Conclusiones. La mesohepatectomía es una alternativa segura para pacientes con tumores en los segmentos centrales, que permite disminuir el riesgo de falla hepática luego de la resección.


Introduction. Surgical resection is the treatment of choice for primary and secondary neoplasms of the liver. Patients with central segment hepatocarcinoma represent a challenge, with extended hepatectomy being the most widely used technique. However, the postsurgical risk of liver failure is high since resection can compromise between 65% and 80% of liver volume. Mesohepatectomy is an alternative that allows a sufficient residual liver volume to be left. The objective of this work is to present treatment of patients with central segment hepatocarcinoma.Clinical cases. Three non-cirrhotic patients are presented, with hepatocarcinoma in segments 4, 5 and 8, who were treated at the San Vicente Fundación Hospital in Medellín and Rionegro, between 2018 and 2020.Results. Mesohepatectomy was performed by selective ligation of the pedicles of segment 4 and the right anterior sector. An ultrasonic aspirator and endostapler were used for liver transection. The duration of the Pringle ma-neuver ranged from 16 to 43 minutes. The average bleeding was 1000 cc. Only one patient had type B bile leakage. There was no 30-day mortality.Conclusions. Mesohepatectomy is a safe alternative for patients with tumors in the central segments, which reduces the risk of liver failure after resection.


Subject(s)
Humans , Liver Failure , Carcinoma, Hepatocellular , Liver Cirrhosis , Hepatectomy
3.
Rev. cuba. med. mil ; 50(3): e1095, 2021. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1357318

ABSTRACT

Introducción: El carcinoma hepatocelular es un tumor hipervascular compuesto por vasos sanguíneos anormales, constituye la forma más frecuente de cáncer primario del hígado. Alrededor del 90 por ciento de estos tumores se desarrollan sobre una enfermedad hepática previa. Un aumento en la carga vascular debido a la hipertensión portal conlleva a sangrado. Objetivo: Presentar un paciente a quien se le practicó laparotomía exploradora de urgencia por hemoperitoneo de gran cuantía secundario a una rotura intratumoral sobre un hígado cirrótico. Caso clínico: Paciente de 66 años de edad, con antecedentes patológicos de diabetes mellitus tipo 2, hiperplasia benigna de próstata, alcoholismo crónico y cirrosis hepática. Acudió al cuerpo de guardia por dolor abdominal difuso y signos de hipovolemia aguda. Se realizó laparotomía de urgencia y se constata hemoperitoneo de gran cuantía, secundario a una rotura intratumoral. Se le realizó aspiración de contenido hemático, electrocoagulación y compresión por empaquetamiento. Se controló el sangrado. El paciente tuvo una evolución tórpida y falleció 24 horas posteriores a la laparotomía. Conclusiones: El hemoperitoneo secundario a rotura de un carcinoma hepatocelular, es una complicación poco frecuente, pero fatal; por lo que se hace necesario su estudio para lograr un diagnóstico y tratamiento oportuno(AU)


Introduction: Hepatocellular carcinoma is a hypervascular tumor made up of abnormal blood vessels. It is the most frequent form of primary liver cancer. About 90 percent of these tumors develop over a previous liver disease. An increase in vascular load due to portal hypertension leads to bleeding. Objective: To present a patient who underwent emergency exploratory laparotomy due to large hemoperitoneum secondary to an intratumoral rupture of a cirrhotic liver. Clinical case: A 66-year-old male patient with a pathological history of type 2 diabetes mellitus, benign prostatic hyperplasia, chronic alcoholism and liver cirrhosis. He came to emergency due to diffuse abdominal pain, as well as signs of acute hypovolemia. An emergency laparotomy was performed, confirming a large hemoperitoneum secondary to an intratumoral rupture. Blood content aspiration, electrocoagulation and compression by packing were performed, managing to control bleeding. He had a torpid evolution, dying 24 hours after the laparotomy. Conclusions: Hemoperitoneum secondary to rupture of a hepatocellular carcinoma is a rare, but fatal complication; therefore, its study is necessary to achieve a timely diagnosis and treatment(AU)


Subject(s)
Humans , Male , Aged , Prostatic Hyperplasia , Carcinoma, Hepatocellular , Hypovolemia , Hemoperitoneum , Liver Cirrhosis , Liver Neoplasms
4.
Electron. j. biotechnol ; 52: 21-29, July. 2021. ilus, tab, graf
Article in English | LILACS | ID: biblio-1283484

ABSTRACT

BACKGROUND: Super-paramagnetic iron oxide nanoparticles (SPION) contain a chemotherapeutic drug and are regarded as a promising technique for improving targeted delivery into cancer cells. RESULTS: In this study, the fabrication of 5-fluorouracil (5-FU) was investigated with loaded Dextran (DEXSPION) using the co-precipitation technique and conjugated by folate (FA). These nanoparticles (NPs) were employed as carriers and anticancer compounds against liver cancer cells in vitro. Structural, magnetic, morphological characterization, size, and drug loading activities of the obtained FA-DEX-5-FUSPION NPs were checked using FTIR, VSM, FESEM, TEM, DLS, and zeta potential techniques. The cellular toxicity effect of FA-DEX-5-FU-SPION NPs was evaluated using the MTT test on liver cancer (SNU-423) and healthy cells (LO2). Furthermore, the apoptosis measurement and the expression levels of NF-1, Her-2/neu, c-Raf-1, and Wnt-1 genes were evaluated post-treatment using flow cytometry and RT-PCR, respectively. The obtained NPs were spherical with a suitable dispersity without noticeable aggregation. The size of the NPs, polydispersity, and zeta were 74 ± 13 nm, 0.080 and 45 mV, respectively. The results of the encapsulation efficiency of the nano-compound showed highly colloidal stability and proper drug maintenance. The results indicated that FA-DEX-5-FU-SPION demonstrated a sustained release profile of 5-FU in both phosphate and citrate buffer solutions separately, with higher cytotoxicity against SNU-423 cells than against other cells types. These findings suggest that FA-DEX-SPION NPs exert synergistic effects for targeting intracellular delivery of 5-FU, apoptosis induction, and gene expression stimulation. CONCLUSIONS: The findings proved that FA-DEX-5-FU-SPION presented remarkable antitumor properties; no adverse subsequences were revealed against normal cells.


Subject(s)
Humans , Carcinoma, Hepatocellular/drug therapy , Fluorouracil/administration & dosage , Liver Neoplasms/drug therapy , Polymers , Gene Expression/drug effects , Drug Delivery Systems , Apoptosis/drug effects , Reverse Transcriptase Polymerase Chain Reaction , Delayed-Action Preparations , Nanoparticles/administration & dosage , Magnetite Nanoparticles , Flow Cytometry
5.
Int. j. med. surg. sci. (Print) ; 8(2): 1-12, jun. 2021. graf, ilus
Article in English | LILACS | ID: biblio-1284445

ABSTRACT

Background/aim: Autophagic cell death and apoptosis of tumor cells has become one of the main objectives in cancer treatment, whereas tumor cell lines are mainly used in studies for providing important data for the evaluation of potential anti cancer substances. In this study, our objective was to evaluate morphological and biochemical changes including rate of apoptosis and Alpha Fetoprotein (AFP) levels at different concentrations of Carnosic Acid (CA) on Human Hepatocellular Carcinoma HepG2 Cells.Materials and methods: Human Hepatocellular Carcinoma (7th passage HepG2 cells) Cell lines were cultured on 11 µM D263M schott glass coverslips placed in 12-well plates and were treated with DMSO, 1, 2.5, 5 and 10 µM concentrations of CA for 24, 48 and 72 hours. Morphological and biochemical data were recorded daily including apoptosis rates demonstrated by Caspase 3, Annexin V expressions under inverted light and Immunofluorescence microscopy, then data were analyzed for statistical significance. AFP, albumin and total protein levels were analyzed spectrophotometricaly for biochemical evaluation.Results: Our results showed that CA significantly inhibited HepG2 cell proliferation in a dose and time dependant manner and significantly caused the formation of autophagic vacuoles starting from 5µM and reaching significance at 10 µM concentrations. Significant decrease was observed in AFP when 48 and 72 hours expressions were examined, with the lowest level reached at 72 hours in the 10 µM CA group. Additionally, increase in albumin levels reached significance only in the 48 h group whereas non-significant increases were also observed in 24 h and 72 h groups.Conclusion: Our current study demonstrates significant increase in apoptosis rates by Carnosic Acid mainly at 10µM concentrations, supporting its anticancer effect on HepG2 cells. These findings are also supported by changes in biochemical analyses of Albumin and AFP levels at 10 µM concentrations.


Antecedentes / objetivos: La muerte celular autofágica y la apoptosis de células tumorales se ha convertido en uno de los principales objetivos en el tratamiento del cáncer, mientras que las líneas celulares tumorales se utilizan principalmente en estudios para proporcionar datos importantes para la evaluación de posibles sustancias anticancerígenas. En este estudio, nuestro objetivo fue evaluar los cambios morfológicos y bioquímicos, incluida la tasa de apoptosis y los niveles de alfa fetoproteína (AFP) a diferentes concentraciones de ácido carnósico (CA) en células de carcinoma hepatocelular humano HepG2.Materiales y métodos: Carcinoma hepatocelular humano (HepG2).Las líneas celulares se cultivaron en cubreobjetos de vidrio Schott D263M de 11 µM colocados en placas de 12 pocillos y se trataron con DMSO, concentraciones de CA 1, 2,5, 5 y 10 µM durante 24, 48 y 72 horas. Los datos morfológicos y bioquímicos se registraron diariamente, incluidas las tasas de apoptosis demostradas por Caspasa 3, las expresiones de Anexina V bajo luz invertida y microscopía de inmunofluorescencia, luego se analizaron los datos para determinar la significación estadística. Los niveles de AFP, albúmina y proteínas totales se analizaron espectrofotométricamente para evaluación bioquímica.Resultados: Nuestros resultados mostraron que CA inhibió significativamente la proliferación de células HepG2 de una manera dependiente de la dosis y el tiempo y causó significativamente la formación de vacuolas autofágicas comenzando desde 5 µM y alcanzando significancia a concentraciones de 10 µM. Se observó una disminución significativa en la AFP cuando se examinaron las expresiones de 48 y 72 horas, alcanzando el nivel más bajo a las 72 horas en el grupo de CA 10 µM. Además, el aumento en los niveles de albúmina alcanzó significación solo en el grupo de 48 h, mientras que también se observaron aumentos no significativos en los grupos de 24 hy 72 h.Conclusión: Nuestro estudio demuestra un aumento significativo en las tasas de apoptosis por el ácido carnósico principalmente a concentraciones de 10 µM, lo que respalda su efecto anticancerígeno en las células HepG2. Estos hallazgos también están respaldados por cambios en los análisis bioquímicos de los niveles de albúmina y AFP a concentraciones de 10 µM.


Subject(s)
Humans , Carcinoma, Hepatocellular/drug therapy , Abietanes/administration & dosage , Hep G2 Cells/drug effects , Liver Neoplasms/drug therapy , Cell Survival , Cells, Cultured , Apoptosis/drug effects , Microscopy, Fluorescence
6.
Rev. Assoc. Méd. Rio Gd. do Sul ; 65(2): 01022105, Abr. - Jun. 2021.
Article in Portuguese | LILACS | ID: biblio-1367471

ABSTRACT

RESUMO A hemocromatose hereditária (HH) é uma doença genética autossômica recessiva, a mais comum encontrada em caucasianos, causada pelo acúmulo de ferro em diferentes órgãos, predominantemente no fígado, causando sua disfunção. As mutações hereditárias relacionadas ao gene HFE representam quase 90% dos casos de hemocromatose entre as populações de descendência europeia. A absorção excessiva do ferro ocasiona acúmulo em órgãos como coração, pâncreas e fígado ocasionando diversas manifestações clínicas. Além dos sintomas gerais, a progressiva sobrecarga de ferro causa uma das principais complicações, a cirrose hepática. A regressão da fibrose pode ser alcançada após o tratamento, promovendo a remoção do estímulo e restaurando a função do fígado. Caso a HH não seja tratada ou o tratamento não tenha sido efetivo, o paciente pode evoluir para um estado fibrótico de cirrose irreversível, que pode culminar com o carcinoma hepatocelular (CHC), complicação responsável por 45% das mortes em pacientes com HH. Nesse sentido, nota-se a importância de compreender os métodos diagnósticos, rastreamento e tratamento, de maneira a possibilitar manejos precoces e evitar complicações potencialmente fatais. Além disso, o fato da população dos estados do sul do Brasil ser composta em sua maioria por descendentes norte-europeus - os mais acometidos pela HH - justifica a importância de literaturas e estudos clínicos mais recentes e realizados nessa região com o objetivo de compreender a evolução clínica da doença e estabelecer medidas preventivas para a manifestação de lesões hepáticas. PALAVRAS-CHAVE: Hemocromatose, HFE, diagnóstico, cirrose hepática, carcinoma hepatocelular


ABSTRACT Hereditary hemochromatosis (HH) is an autosomal recessive genetic disease, the most common found in Caucasians, caused by the accumulation of iron in different organs, predominantly in the liver, causing its dysfunction. Inherited mutations related to the HFE gene represent almost 90% of cases of hemochromatosis among populations of European descent. Excessive iron absorption causes accumulation in organs such as the heart, pancreas and liver, causing several clinical manifestations. In addition to the general symptoms, progressive iron overload causes one of the main complications, liver cirrhosis. Regression of fibrosis can be achieved after treatment, promoting stimulus removal and restoring liver function. If HH is not treated or the treatment has not been effective, the patient may progress to a fibrotic state of irreversible cirrhosis, which can culminate in hepatocellular carcinoma (HCC), a complication responsible for 45% of deaths in patients with HH. In this sense, the importance of understanding diagnostic methods, screening and treatment is noted, in order to enable early management and avoid potentially fatal complications. In addition, the fact that the population of the southern states of Brazil is composed mostly of North European descendants ­ the most affected by HH ­ justifies the importance of more recent literature and clinical studies carried out in this region in order to understand the clinical course of the disease and establish preventive measures for the manifestation of liver damage. KEYWORDS: Hemochromatosis, HFE, diagnosis, liver cirrhosis, hepatocellular carcinoma


Subject(s)
Humans , Diagnosis , Hemochromatosis Protein , Hemochromatosis , Liver Cirrhosis , Carcinoma, Hepatocellular
7.
Medicina (B.Aires) ; 81(3): 346-358, jun. 2021. graf
Article in English | LILACS | ID: biblio-1346469

ABSTRACT

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Hexachlorobenzene (HCB) is an endocrine disruptor and a liver tumor promoter. Deregulation of thyroid hormone (TH) homeostasis may play a significant role in early neoplastic transformation. The aim of this study was to evaluate the relation between TH metabolism and the regulation of cell growth in an in vivo and in vitro model. We examined the role of transforming growth factor-β1 (TGF-β1) on TH deiodinase expression and hepatocyte proliferation. An initiation (DEN)/promotion (HCB) tumor model from rat liver and HepG2 cells were used. We evaluated PCNA, p21, p27, SMAD2/3, TGF-β1, deiodinase 1 (D1), D3, protein expression levels; D1 and D3 mRNA expression; TH and TGF-β1, D1, D3, and GST-P protein levels in focal/non-focal areas. In vivo, HCB decreased triiodothyronine (T3) and D1 mRNA levels and increased thyroxine (T4) and D3 mRNA levels in liver from DEN+HCB vs. DEN group. HCB increased protein levels from D3, TGF-β1, and PCNA and decreased D1 in focal-areas. In vitro, HCB increased PCNA, pSMAD 2/3, and TGF-β1 protein levels and mRNA expression and decreased p21 and p27 protein levels. Exogenous T3 treatment prevent HCB induced molecular alterations related to hepatocyte proliferation whereas T4 did not have any effect. These effects were prevented by using a TGF-β1 receptor II inhibitor. Results suggest that alteration of TH homeostasis, through D1 function, play a key role in hepatocyte proliferation and that TGF-β1-SMAD pathway is involved in this process confirming their role in early neoplastic transformation in HCC.


Resumen El hepatocarcinoma (HCC) es un tumor hepático primario. El hexaclorobenceno (HCB) es un disruptor endocrino y un promotor de tumores hepáticos. La desregulación de la homeostasis de las hormonas tiroideas (HT) puede ser un proceso importante para la transformación neoplásica temprana. Nuestro objetivo fue evaluar la relación entre el metabolismo de las HT y la regulación de la prolifera ción celular. Se utilizó un modelo tumoral de iniciación (DEN)/promoción (HCB) de hígado de rata (in vivo) (DEN/ HCB) y células HepG2 (in vitro). Evaluamos los niveles de PCNA, p21, p27, SMAD2/3, TGF-β1, D1, D3, ARNm de D1 y D3, HT y los niveles de TGF-β1, D1, D3 y GST-P en áreas focales/no focales. In vivo, HCB disminuyó los niveles de T3 y ARNm de la D1 y aumentó los niveles de T4 y ARNm de D3 del grupo DEN + HCB frente al grupo DEN. El HCB aumentó los niveles de D3, TGF-β1 y PCNA y disminuyó el D1 en las áreas focales. In vitro, HCB aumentó los niveles de PCNA, pSMAD 2/3 y TGF-β1 y la expresión de ARNm mientras que disminuyó los niveles de p21 y p27. El tratamiento con T3 exógeno previno las alteraciones moleculares relacionadas con la proliferación hepatocitaria. Estos efectos se evitaron utilizando un inhibidor del receptor II de TGF-β1. Los resultados sugieren que la alteración de la homeostasis de HT, a través de la D1 y la vía TGF-β1-SMAD, juega un papel clave en la proliferación celular y en las transformaciones neoplásicas tempranas en el HCC.


Subject(s)
Animals , Rats , Carcinoma, Hepatocellular , Transforming Growth Factor beta1 , Iodide Peroxidase/genetics , Liver Neoplasms , Cell Proliferation
8.
Arq. gastroenterol ; 58(1): 82-86, Jan.-Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1248979

ABSTRACT

ABSTRACT BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver and cirrhosis is considered a pre-malignant disease. In this context, the evolutionary sequence from low grade dysplastic nodule and high grade dysplastic nodule (HGDN) to early HCC and advanced HCC has been studied. The differential diagnosis between HGDN and early HCC is still a challenge, especially in needle biopsies OBJECTIVE: To evaluate an immunohistochemistry panel to differentiate dysplastic nodules and HCC. METHODS: Patients with cirrhosis who underwent surgical resection or liver transplantation were included. The sensitivity, specificity and accuracy for the diagnosis of neoplasia were analyzed by evaluating five markers: heat shock protein 70, glypican 3, glutamine synthetase, clathrin heavy chain and beta-catenin. P≤0.05 was considered statistically significant. RESULTS: One hundred and fifty-six nodules were included; of these, 57 were HCC, 14 HGDN, 18 low grade dysplastic nodules and 67 regenerative macronodules. Sensitivity of HCC diagnosis was 64.9% for glypican 3 and 77.2% for glutamine syntetase, while specificity was 96.0% and 96.0% respectively. When the panel of four markers was considered (excluding beta catenin), the specificity ranged from 87.9% for one positive marker to 100% for at least three markers. The best accuracy for HCC diagnosis was obtained with at least two positive markers, which was associated with a sensitivity of 82.5% and specificity of 99%. CONCLUSION: Differential diagnosis of dysplastic nodules and HCC by morphological criteria can be challenging. Immunomarkers are useful and should be used for the differential diagnosis between HCC and HGDN.


RESUMO CONTEXTO: O carcinoma hepatocelular (CHC) é o câncer primário do fígado mais frequente e a cirrose é considerada uma doença pré-maligna. Nesse contexto, a sequência evolutiva do nódulo displásico de baixo grau e nódulo displásico de alto grau (NDAG) para CHC precoce e CHC avançado tem sido estudada. O diagnóstico diferencial entre NDAG e CHC precoce ainda é um desafio, principalmente em biópsias por agulha. OBJETIVO: Avaliar um painel de imunohistoquímica para diferenciar nódulos displásicos de CHC. MÉTODOS: Foram incluídos pacientes com cirrose submetidos à ressecção cirúrgica ou transplante de fígado. A sensibilidade, especificidade e acurácia para o diagnóstico da neoplasia foram analisadas avaliando cinco marcadores: proteína de choque térmico 70kDa, glipican 3, glutamina sintetase, clatrina de cadeia pesada e beta-catenina. P≤0,05 foi considerado estatisticamente significativo. RESULTADOS: Cento e cinquenta e seis nódulos foram incluídos; destes, 57 eram CHC, 14 NDAG, 18 nódulos displásicos de baixo grau e 67 macronódulos regenerativos. A sensibilidade do diagnóstico de CHC foi de 64,9% para glipican 3 e 77,2% para glutamina sintetase, enquanto a especificidade foi de 96,0% e 96,0%, respectivamente. Quando o painel de quatro marcadores foi considerado (excluindo beta catenina), a especificidade variou de 87,9% para um marcador positivo a 100% para pelo menos três marcadores. A melhor acurácia para o diagnóstico de CHC foi obtida com pelo menos dois marcadores positivos, o que foi associado a uma sensibilidade de 82,5% e especificidade de 99%. CONCLUSÃO: O diagnóstico diferencial de nódulos displásicos e CHC por critérios morfológicos pode ser desafiador. Imunomarcadores são úteis e devem ser usados para o diagnóstico diferencial entre CHC e NDAG.


Subject(s)
Humans , Carcinoma, Hepatocellular/diagnosis , Neoplasms/diagnosis , Immunohistochemistry , Diagnosis, Differential , Liver Cirrhosis/diagnosis
9.
Chinese Medical Journal ; (24): 1181-1190, 2021.
Article in English | WPRIM | ID: wpr-878169

ABSTRACT

BACKGROUND@#Pre-operative non-invasive histological evaluation of hepatocellular carcinoma (HCC) remains a challenge. Tumor perfusion is significantly associated with the development and aggressiveness of HCC. The purpose of the study was to evaluate the clinical value of quantitative liver perfusion parameters and corresponding histogram parameters derived from traditional triphasic enhanced computed tomography (CT) scans in predicting histological grade of HCC.@*METHODS@#Totally, 52 patients with HCC were enrolled in this retrospective study and underwent triple-phase enhanced CT imaging. The blood perfusion parameters were derived from triple-phase CT scans. The relationship of liver perfusion parameters and corresponding histogram parameters with the histological grade of HCC was analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal ability of the parameters to predict the tumor histological grade.@*RESULTS@#The variance of arterial enhancement fraction (AEF) was significantly higher in HCCs without poorly differentiated components (NP-HCCs) than in HCCs with poorly differentiated components (P-HCCs). The difference in hepatic blood flow (HF) between total tumor and total liver flow (ΔHF = HFtumor - HFliver) and relative flow (rHF = ΔHF/HFliver) were significantly higher in NP-HCCs than in P-HCCs. The difference in portal vein blood supply perfusion (PVP) between tumor and liver tissue (ΔPVP) and the ΔPVP/liver PVP ratio (rPVP) were significantly higher in patients with NP-HCCs than in patients with P-HCCs. The area under ROC (AUC) of ΔPVP and rPVP were both 0.697 with a high sensitivity of 84.2% and specificity of only 56.2%. The ΔHF and rHF had a higher specificity of 87.5% with an AUC of 0.681 and 0.673, respectively. The combination of rHF and rPVP showed the highest AUC of 0.732 with a sensitivity of 57.9% and specificity of 93.8%. The combined parameter of ΔHF and rPVP, rHF and rPVP had the highest positive predictive value of 0.903, and that of rPVP and ΔPVP had the highest negative predictive value of 0.781.@*CONCLUSION@#Liver perfusion parameters and corresponding histogram parameters (including ΔHF, rHF, ΔPVP, rPVP, and AEFvariance) in patients with HCC derived from traditional triphasic CT scans may be helpful to non-invasively and pre-operatively predict the degree of the differentiation of HCC.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Contrast Media , Humans , Liver Neoplasms/diagnostic imaging , Perfusion , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray Computed
10.
Rev. bras. cancerol ; 67(2): e-121220, 2021.
Article in Portuguese | LILACS | ID: biblio-1254344

ABSTRACT

Introdução: A hepatite C está associada ao desenvolvimento do carcinoma hepatocelular (CHC). O regime terapêutico baseado em interferon vem sendo substituído pelos antivirais de ação direta (AAD) para tratamento da infecção pelo vírus da hepatite C (HCV). Contudo, estudos recentes evidenciaram um aumento inesperado da recorrência do CHC em pacientes tratados com AAD para resolução da hepatite C. Objetivo: Avaliar o risco de recorrência de hepatocarcinoma após uso de AAD em pacientes com infecção por HCV. Método: Realizou-se um levantamento nas bases de dados PubMed, MEDLINE e LILACS de acordo com os descritores DeCS/MeSH ((hepatocellular carcinoma) AND recurrence) AND Direct-acting antiviral. A revisão obedeceu ao protocolo PRISMA e está cadastrada na plataforma PROSPERO. A análise estatística dos dados foi realizada no software RStudio. Resultados: Sete artigos foram selecionados resultando em 847 pacientes. Entre os tratados com AAD, a taxa de recorrência variou entre 11,1% e 42,1% e, no grupo controle, ocorreu em 5% a 65,6% dos pacientes. O risco relativo (RR) de recorrência do CHC no grupo de pacientes que recebeu AAD foi menor do que o risco evidenciado no grupo controle, apesar de não haver significância estatística (RR 0,71 95% IC [0,55;0,93] I²=38%, p=0,14). O tempo até o diagnóstico da recorrência teve uma média de 9,35 meses no grupo exposto à terapia e 13,42 meses no grupo controle. Conclusão: Sugere-se que a terapia com AAD não aumenta o risco de recorrência do CHC em comparação com grupos controle. Nos pacientes que desenvolveram recorrência, ocorreu com maior frequência dentro do primeiro ano após introdução dos AAD.


Introduction: Hepatitis C is associated with the development of hepatocellular carcinoma (HCC). The interferon-based therapeutic regimen has been replaced by direct-acting antivirals (AAD) to treat HCV virus infection. However, recent studies have shown an unexpected increase in HCC recurrence in patients treated with AAD to resolve hepatitis C. Objective: To assess the risk of hepatocarcinoma recurrence after using AAD in patients with HCV infection. Method: A survey was carried out in PubMed, MEDLINE, and LILACS databases according to the descriptors DeCS/MeSH ((hepatocellular carcinoma) AND recurrence) AND Direct-acting antiviral. The review followed the PRISMA protocol and is registered on the PROSPERO platform. The data statistical analysis was performed through RStudio software. Results: Seven articles were selected resulting in 847 patients. Among those treated with AAD, the recurrence rate varied between 11.1% to 42.1% and, in the control group, it occurred in 5% to 65.6% of the patients. The relative risk (RR) of recurrence of HCC in the group of patients who received AAD was less than the risk evidenced in the control group, although there is no statistical significance (RR 0.71 95% CI [0.55; 0.93] I²=38%, p=0.14). The mean time until the diagnosis of recurrence was 9.35 months in the group exposed to therapy and 13.42 months in the control group. Conclusion: It is suggested that therapy with AAD does not increase the risk of HCC recurrence compared to control groups. In patients who developed recurrence, it occurred more frequently within the first year after the introduction of AAD.


Introducción: La hepatitis C está asociada con el desarrollo de carcinoma hepatocelular (CHC). El régimen terapéutico basado en interferón ha sido reemplazado por antivirales de acción directa (AAD) para tratar la infección por VHC. Sin embargo, estudios recientes han mostrado un incremento inesperado en la recurrencia del CHC en pacientes tratados con AAD para resolución de la hepatitis C. Objetivo: Evaluar el riesgo de recurrencia del hepatocarcinoma después de usar AAD en pacientes con infección por VHC. Método: Se realizó una pesquisa en las bases de datos PubMed, MEDLINE y LILACS según los descriptores DeCS/MeSH ((carcinoma hepatocelular) AND recurrencia) AND antiviral de acción directa. La revisión siguió el protocolo PRISMA y está registrada en la plataforma PROSPERO. El análisis estadístico de los datos se realizó mediante el software RStudio. Resultados: Fueron seleccionados 7 artículos resultando en 847 pacientes. Entre los tratados con AAD, la tasa de recurrencia varió entre el 11,1% y el 42,1% y, en el grupo de control, ocurrió entre el 5% y el 65,6% de los pacientes. El riesgo relativo (RR) de recurrencia del CHC en el grupo de pacientes que recibieron AAD fue inferior que el riesgo evidenciado en el grupo control, aunque no hay significación estadística (RR 0,71; IC del 95% [0,55; 0,93] I²=38%, p=0,14). El tiempo hasta el diagnóstico de recidiva fue de 9,35 meses en el grupo expuesto a terapia y de 13,42 meses en el grupo control. Conclusión: Se sugiere que la terapia con AAD no aumenta el riesgo de recurrencia del CHC en comparación con los grupos control. En los pacientes que desarrollaron recurrencia, esta ocurrió con mayor frecuencia durante el primer año después de la introducción de los AAD.


Subject(s)
Humans , Liver Neoplasms/etiology , Antiviral Agents/therapeutic use , Hepatitis C/complications , Carcinoma, Hepatocellular/etiology , Neoplasm Recurrence, Local
11.
Rev. bras. cancerol ; 67(2): e-121220, 2021.
Article in Portuguese | LILACS | ID: biblio-1254542

ABSTRACT

Introdução: A hepatite C está associada ao desenvolvimento do carcinoma hepatocelular (CHC). O regime terapêutico baseado em interferon vem sendo substituído pelos antivirais de ação direta (AAD) para tratamento da infecção pelo vírus da hepatite C (HCV). Contudo, estudos recentes evidenciaram um aumento inesperado da recorrência do CHC em pacientes tratados com AAD para resolução da hepatite C. Objetivo: Avaliar o risco de recorrência de hepatocarcinoma após uso de AAD em pacientes com infecção por HCV. Método: Realizou-se um levantamento nas bases de dados PubMed, MEDLINE e LILACS de acordo com os descritores DeCS/MeSH ((hepatocellular carcinoma) AND recurrence) AND Direct-acting antiviral. A revisão obedeceu ao protocolo PRISMA e está cadastrada na plataforma PROSPERO. A análise estatística dos dados foi realizada no software RStudio. Resultados: Sete artigos foram selecionados resultando em 847 pacientes. Entre os tratados com AAD, a taxa de recorrência variou entre 11,1% e 42,1% e, no grupo controle, ocorreu em 5% a 65,6% dos pacientes. O risco relativo (RR) de recorrência do CHC no grupo de pacientes que recebeu AAD foi menor do que o risco evidenciado no grupo controle, apesar de não haver significância estatística (RR 0,71 95% IC [0,55;0,93] I²=38%, p=0,14). O tempo até o diagnóstico da recorrência teve uma média de 9,35 meses no grupo exposto à terapia e 13,42 meses no grupo controle. Conclusão: Sugere-se que a terapia com AAD não aumenta o risco de recorrência do CHC em comparação com grupos controle. Nos pacientes que desenvolveram recorrência, ocorreu com maior frequência dentro do primeiro ano após introdução dos AAD.


Introduction: Hepatitis C is associated with the development of hepatocellular carcinoma (HCC). The interferon-based therapeutic regimen has been replaced by direct-acting antivirals (AAD) to treat HCV virus infection. However, recent studies have shown an unexpected increase in HCC recurrence in patients treated with AAD to resolve hepatitis C. Objective: To assess the risk of hepatocarcinoma recurrence after using AAD in patients with HCV infection. Method: A survey was carried out in PubMed, MEDLINE, and LILACS databases according to the descriptors DeCS/MeSH ((hepatocellular carcinoma) AND recurrence) AND Direct-acting antiviral. The review followed the PRISMA protocol and is registered on the PROSPERO platform. The data statistical analysis was performed through RStudio software. Results: Seven articles were selected resulting in 847 patients. Among those treated with AAD, the recurrence rate varied between 11.1% to 42.1% and, in the control group, it occurred in 5% to 65.6% of the patients. The relative risk (RR) of recurrence of HCC in the group of patients who received AAD was less than the risk evidenced in the control group, although there is no statistical significance (RR 0.71 95% CI [0.55; 0.93] I²=38%, p=0.14). The mean time until the diagnosis of recurrence was 9.35 months in the group exposed to therapy and 13.42 months in the control group. Conclusion: It is suggested that therapy with AAD does not increase the risk of HCC recurrence compared to control groups. In patients who developed recurrence, it occurred more frequently within the first year after the introduction of AAD.


Introducción: La hepatitis C está asociada con el desarrollo de carcinoma hepatocelular (CHC). El régimen terapéutico basado en interferón ha sido reemplazado por antivirales de acción directa (AAD) para tratar la infección por VHC. Sin embargo, estudios recientes han mostrado un incremento inesperado en la recurrencia del CHC en pacientes tratados con AAD para resolución de la hepatitis C. Objetivo: Evaluar el riesgo de recurrencia del hepatocarcinoma después de usar AAD en pacientes con infección por VHC. Método: Se realizó una pesquisa en las bases de datos PubMed, MEDLINE y LILACS según los descriptores DeCS/MeSH ((carcinoma hepatocelular) AND recurrencia) AND antiviral de acción directa. La revisión siguió el protocolo PRISMA y está registrada en la plataforma PROSPERO. El análisis estadístico de los datos se realizó mediante el software RStudio. Resultados: Fueron seleccionados 7 artículos resultando en 847 pacientes. Entre los tratados con AAD, la tasa de recurrencia varió entre el 11,1% y el 42,1% y, en el grupo de control, ocurrió entre el 5% y el 65,6% de los pacientes. El riesgo relativo (RR) de recurrencia del CHC en el grupo de pacientes que recibieron AAD fue inferior que el riesgo evidenciado en el grupo control, aunque no hay significación estadística (RR 0,71; IC del 95% [0,55; 0,93] I²=38%, p=0,14). El tiempo hasta el diagnóstico de recidiva fue de 9,35 meses en el grupo expuesto a terapia y de 13,42 meses en el grupo control. Conclusión: Se sugiere que la terapia con AAD no aumenta el riesgo de recurrencia del CHC en comparación con los grupos control. En los pacientes que desarrollaron recurrencia, esta ocurrió con mayor frecuencia durante el primer año después de la introducción de los AAD.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C/complications , Carcinoma, Hepatocellular/etiology , Liver Neoplasms/etiology , Neoplasm Recurrence, Local
12.
J. venom. anim. toxins incl. trop. dis ; 27: e20210039, 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1351021

ABSTRACT

Background Hepatitis C virus (HCV) infection is a major worldwide health problem that can cause liver fibrosis and hepatocellular carcinoma (HCC). The clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) that are usually expensive and have side effects. Therefore, achieving the discovery of more successful agents is always urgent. In this context, antiviral compounds that inhibit viral infections and disease progression with important therapeutic activities have been identified in animal venoms including arthropod toxins. This indicates that arthropod venoms represent a good natural source of promising candidates for new antivirals. Methods The antiviral activity of the wasp venom (WV), isolated from the Oriental hornet (Vespa orientalis), was assessed using cell culture technique with human hepatocellular carcinoma-derived cell line (Huh7it-1) and the recombinant strain of HCV genotype 2a (JFH1). Results The results revealed that WV inhibited HCV infectivity with 50% inhibitory concentration (IC50) of 10 ng/mL, while the 50% cytotoxic concentration (CC50) was 11,000 ng/mL. Time of addition experiment showed that the WV blocked HCV attachment/entry to the cells probably through virucidal effect. On the other hand, the venom showed no inhibitory effect on HCV replication. Conclusion WV can inhibit the entry stage of HCV infection at non-cytotoxic concentrations. Therefore, it could be considered a potential candidate for characterization of natural anti-HCV agents targeting the entry step.(AU)


Subject(s)
Antiviral Agents , Wasp Venoms , Carcinoma, Hepatocellular
13.
Chinese Journal of Oncology ; (12): 60-77, 2021.
Article in Chinese | WPRIM | ID: wpr-877498

ABSTRACT

The age-adjusted incidence of primary liver cancer (PLC) has been declining in China. However, PLC cases in China account for 55% globally. The disease burden is still high and the 5-year survival rate was not improved significantly in the past two decades. This guideline outlines PLC screening in the risk populations, both in hospital and community. Liver cirrhosis and chronic hepatitis B are the main causes of PLC in China. For better PLC surveillance and screening in clinical practices, it is recommended to stratify population at the risk into 4 risk levels, namely, low-risk, intermediate-risk, high-risk, and extremely high-risk. The lifelong surveillance is suggested for those at the risk of PLC. The intervals and tools for surveillance and screening are recommended based on the risk levels. Abdominal ultrasonography combined with serum alpha-fetoprotein examination (routine surveillance) every 6 months is recommended for those at a high risk of PLC. Routine surveillance every 3 months and enhanced CT/MRI examination every 6-12 months are recommended for those at an extremely high risk of PLC. The surveillance interval can be extended every 1 year or longer for those at a low-risk or at an intermediate-risk of PLC, because their annual incidence of PLC is very low. The cost-effectiveness of these recommendations remains to be evaluated.


Subject(s)
Carcinoma, Hepatocellular , China/epidemiology , Early Detection of Cancer , Hepatitis B, Chronic , Humans , Liver Cirrhosis , Liver Neoplasms/epidemiology , Ultrasonography
14.
Chinese Journal of Biotechnology ; (12): 2719-2736, 2021.
Article in Chinese | WPRIM | ID: wpr-887836

ABSTRACT

Primary liver cancer (PLC) is an aggressive tumor and prone to metastasize and recur. According to pathological features, PLC are mainly categorized into hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed hepatocellular cholangiocarcinoma, and fibrolamelic hepatocellular carcinoma, etc. At present, surgical resection, radiotherapy and chemotherapy are still the main treatments for PLC, but the specificities are poor and the clinical effects are limited with a 5-year overall survival rate of 18%. Liver cancer stem cells (LCSCs) are a specific cell subset existing in liver cancer tissues. They harbor the capabilities of self-renewal and strong tumorigenicity, driving tumor initiation, metastasis, drug resistance and recurrence of PLC. Therefore, the identification of molecular markers and the illustration of mechanisms for stemness maintenance of LCSCs can not only reveal the molecular mechanisms of PLC tumorigenesis, but also lay a theoretical foundation for the molecular classification, prognosis evaluation and targeted therapy of PLC. The latest research showed that the combination of 5-fluorouracil and CD13 inhibitors could inhibit the proliferation of CD13+ LCSCs, thereby reducing overall tumor burden. Taken together, LCSCs could be the promising therapeutic targets of PLC in the future. This review summarizes the latest progress in molecular markers, mechanisms for stemness maintenance and targeted therapies of LCSCs.


Subject(s)
Carcinoma, Hepatocellular/genetics , Humans , Liver Neoplasms/genetics , Neoplastic Stem Cells , Prognosis
15.
Frontiers of Medicine ; (4): 155-169, 2021.
Article in English | WPRIM | ID: wpr-880972

ABSTRACT

Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.


Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Chemotherapy, Adjuvant , Hepatectomy , Humans , Liver Neoplasms/therapy , Neoplasm Recurrence, Local , Treatment Outcome
16.
Frontiers of Medicine ; (4): 170-177, 2021.
Article in English | WPRIM | ID: wpr-880966

ABSTRACT

Nanosecond pulsed electric field (nsPEF) is a novel, nonthermal, and minimally invasive modality that can ablate solid tumors by inducing apoptosis. Recent animal experiments show that nsPEF can induce the immunogenic cell death of hepatocellular carcinoma (HCC) and stimulate the host's immune response to kill residual tumor cells and decrease distant metastatic tumors. nsPEF-induced immunity is of great clinical importance because the nonthermal ablation may enhance the immune memory, which can prevent HCC recurrence and metastasis. This review summarized the most advanced research on the effect of nsPEF. The possible mechanisms of how locoregional nsPEF ablation enhances the systemic anticancer immune responses were illustrated. nsPEF stimulates the host immune system to boost stimulation and prevail suppression. Also, nsPEF increases the dendritic cell loading and inhibits the regulatory responses, thereby improving immune stimulation and limiting immunosuppression in HCC-bearing hosts. Therefore, nsPEF has excellent potential for HCC treatment.


Subject(s)
Animals , Carcinoma, Hepatocellular/therapy , Cell Line, Tumor , Immunity , Liver Neoplasms/therapy , Neoplasm Recurrence, Local
17.
Journal of Integrative Medicine ; (12): 469-477, 2021.
Article in English | WPRIM | ID: wpr-922522

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant cancers worldwide. Epithelial-mesenchymal transition (EMT), which endows epithelial cells with mesenchymal properties, plays an important role in the early stages of metastasis. Conventional cancer therapies have promising effects, but issues remain, such as high rates of metastasis and drug resistance. Thus, exploring and evaluating new therapies is an urgent need. Traditional Chinese medicines (TCMs) have been acknowledged for their multi-target and coordinated intervention effects against HCC. Accumulating evidence indicates that TCM can inhibit the malignancy of cells and the progression of EMT in HCC. However, studies on the effects of TCM on EMT in HCC are scarce. In this review, we summarized recent developments in anti-EMT TCMs and formulae, focusing on their underlying pharmacological mechanisms, to provide a foundation for further research on the exact mechanisms through which TCM affects EMT in HCC.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Epithelial-Mesenchymal Transition , Humans , Liver Neoplasms/drug therapy , Medicine, Chinese Traditional
18.
Protein & Cell ; (12): 788-809, 2021.
Article in English | WPRIM | ID: wpr-922475

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.


Subject(s)
Adult , Aged , Animals , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Intracellular Signaling Peptides and Proteins/metabolism , /metabolism , Liver Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Middle Aged , Neoplasm Staging , Prognosis , Protein Binding , RNA, Small Interfering/metabolism , Survival Analysis , Tumor Burden , Wnt Signaling Pathway , Xenograft Model Antitumor Assays , beta Catenin/metabolism
19.
Article in English | WPRIM | ID: wpr-921867

ABSTRACT

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the fourth leading cause of cancer related death worldwide. China covers over half of cases, leading HCC to be a vital threaten to public health. Despite advances in diagnosis and treatments, high recurrence rate remains a major obstacle in HCC management. Multi-omics currently facilitates surveillance, precise diagnosis, and personalized treatment decision making in clinical setting. Non-invasive radiomics utilizes preoperative radiological imaging to reflect subtle pixel-level pattern changes that correlate to specific clinical outcomes. Radiomics has been widely used in histopathological diagnosis prediction, treatment response evaluation, and prognosis prediction. High-throughput sequencing and gene expression profiling enabled genomics and proteomics to identify distinct transcriptomic subclasses and recurrent genetic alterations in HCC, which would reveal the complex multistep process of the pathophysiology. The accumulation of big medical data and the development of artificial intelligence techniques are providing new insights for our better understanding of the mechanism of HCC via multi-omics, and show potential to convert surgical/intervention treatment into an antitumorigenic one, which would greatly advance precision medicine in HCC management.


Subject(s)
Artificial Intelligence , Carcinoma, Hepatocellular/therapy , Gene Expression Profiling , Humans , Liver Neoplasms/genetics , Prognosis
20.
Chinese Journal of Biotechnology ; (12): 4124-4133, 2021.
Article in Chinese | WPRIM | ID: wpr-921493

ABSTRACT

The existence of cancer stem cells is regarded as the major cause for therapeutic resistance and relapse of a variety of cancer types including hepatocellular carcinoma (HCC). However, the tracing of such a subpopulation in vivo has been challenging. We have previously demonstrated that the isoform 5 of the voltage-gated calcium channel α2δ1 subunit, which can be recognized specifically by a monoclonal antibody 1B50-1, is a bona fide surface marker for HCC stem cells. Here we developed a strategy for optical imaging of α2δ1-positive cells by using a fusion protein containing the single chain variable fragment (scFv) of Mab1B50-1 and the luciferase NanoLuc which was tagged with Flag in the C-terminal. The scFv of Mab1B50-1 was fused to the N-terminal of NanoLucFlag using overlap PCR, and the recombinant fragment, which was named as 1B50-1scFv-NanoLucFlag, was subsequently cloned into a eukaryotic expression vector. The resulting construct was transfected into FreeStyle 293F cells in suspension using PEI reagent. The expression of the fusion protein was identified as a protein with molecular weight about 50 kDa by Western blotting. After purification by ANTI-FLAG® M2 affinity chromatography, 1B50-1scFv-NanoLucFlag was demonstrated to bind to α2δ1 positive cells specifically with a Kd value of (18.62±1.84) nmol/L. Furthermore, a strong luciferase activity of 1B50-1scFv-NanoLucFlag was detected in α2δ1 positive cells following incubation with the fusion protein, indicating that the presence of α2δ1 could be quantified using this fusion protein. Hence, 1B50-1scFv-NanoLucFlag provides a potential tool for optical imaging of α2δ1 positive cancer stem cells both in vitro and in vivo.


Subject(s)
Carcinoma, Hepatocellular , Humans , Liver Neoplasms , Neoplastic Stem Cells , Recombinant Proteins/genetics , Single-Chain Antibodies/genetics
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