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1.
Braz. j. biol ; 84: e250575, 2024. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1350309

ABSTRACT

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.


Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.


Subject(s)
Humans , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Liver Neoplasms , Prognosis , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Up-Regulation , DNA-Binding Proteins , DNA Copy Number Variations
2.
Braz. j. biol ; 84: e253183, 2024. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1355858

ABSTRACT

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.


Resumo Nanopartículas são consideradas opções viáveis ​​no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.


Subject(s)
Animals , Rats , Magnetite Nanoparticles , Liver Neoplasms , Ferric Compounds , Folic Acid
3.
Braz. j. biol ; 82: e256856, 2022. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1355846

ABSTRACT

Abstract The aim of the present study was to evaluate the in vitro antiproliferative activity of ethanolic extract of leaves and fruits Citrus paradisi plant on HepG-2 liver cell lines by MTT (3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-terazolium bromide) assay and to isolate and characterize the antiproliferative compounds by TLC (Thin layer chromatography) and FT-IR (Fourier transforms Infrared) spectroscopy. Qualitative phytochemical screening tests were performed to detect phytochemicals compounds from the crude extracts. Antioxidant activity of the plant extracts were characterized by using DPPH (2,2-Diphenyl-1-picrylhydrazyl) free radical scavenging method. The results showed that antioxidant activity using DPPH were found to be increased in a concentration dependent manner and decreased cell viability and cell growth inhibition in a dose dependent manner. The findings from this study indicated that fruit extract exhibited good antiproliferation and antioxidant potential. The seven functional groups of phytocompounds such as carboxylic acid, amine salt, aromatic compounds, cyclic alkene, aldehyde, fluoro compounds and alkene were detected by FT-IR which indicated that fruit extracts of Citrus paradisi possessed vast potential as a medicinal drug especially in liver cancer treatment.


Resumo O objetivo do presente estudo foi avaliar a atividade antiproliferativa in vitro do extrato etanólico de folhas e frutos da planta Citrus paradisi em linhagens de células hepáticas HepG-2 por MTT (3- (4, 5-dimetil-2-tiazolil) -2, Ensaio de brometo de 5-difenil-2H-terazólio) e isolar e caracterizar os compostos antiproliferativos por espectroscopia de TLC (cromatografia de camada fina) e FT-IR (infravermelho com transformadas de Fourier). Testes qualitativos de triagem fitoquímica foram realizados para detectar compostos fitoquímicos nos extratos brutos. A atividade antioxidante dos extratos vegetais foi caracterizada pelo método de eliminação de radicais livres DPPH (2,2-difenil-1-picrilhidrazil). Os resultados mostraram que a atividade antioxidante usando DPPH aumentou de uma maneira dependente da concentração e diminuiu a viabilidade celular e a inibição do crescimento celular de uma maneira dependente da dose. Os resultados deste estudo indicaram que o extrato de fruta exibiu bom potencial antiproliferação e antioxidante. Os sete grupos funcionais de fitocompostos, como ácido carboxílico, sal de amina, compostos aromáticos, alceno cíclico, aldeído, compostos de flúor e alceno, foram detectados por FT-IR, o que indicou que extratos de frutas de Citrus paradisi possuíam vasto potencial como medicamento, especialmente no tratamento de câncer do fígado.


Subject(s)
Humans , Citrus paradisi , Liver Neoplasms/drug therapy , Plant Extracts/pharmacology , Cell Line , Spectroscopy, Fourier Transform Infrared , Phytochemicals , Antioxidants
4.
Rev. ecuat. pediatr ; 22(3): 1-10, 30 de diciembre del 2021.
Article in Spanish | LILACS | ID: biblio-1352456

ABSTRACT

Introducción: La resección hepática sigue siendo el método más efectivo de tratamiento de tumores hepáticos. Actualmente, el abordaje laparoscópico se considera como el estándar de oro frente al abordaje abierto; sin embargo, el surgimiento de la cirugía robótica brinda una nueva opción de abordaje mínimamente invasiva con aparentes mejores resultados. El objeti-vo de esta revisión sistemática es valorar los beneficios de la hepatectomía robótica frente a la hepatectomía laparoscópica en la resección de tumores hepáticos. Metodología: En esta revisión sistemática se incluirán estudios comparativos, de cohorte, de casos y controles, con recolección de datos prospectivos o retrospectivos. Los participantes de los estudios serán pacientes diagnosticados con tumores hepáticos benignos o malignos, in-cluidos niños y adolescentes, no cirróticos o cirróticos compensados sometidos a intervencio-nes de hepatectomía robótica y hepatectomía laparoscópica. Las medidas de resultado pri-marias son: 1. Pérdida de sangre estimada durante el acto quirúrgico, 2. Tiempo operatorio, 3. Tasa de conversión a laparotomía, 4. Tasa de mortalidad intraoperatoria, 5. Tasa de morbili-dad (complicaciones postquirúrgicas), 6. Estancia hospitalaria postquirúrgica. Las búsquedas electrónicas se realizarán en PUBMED, MEDLINE, SCIENCEDIRECT (2010 hasta el presente). Se usará la evaluación del riesgo de sesgo de estudios de Cochrane. Como medidas de efecto del tratamiento se utilizarán las diferencias de medias (DM) y los intervalos de confianza (IC) del 95. La evaluación de heterogeneidad se realizará mediante la inspección visual del diagrama de embudo. La evaluación de la calidad de la evidencia y tablas de 'Resumen de hallazgos' se usará el test GRADE.


Introduction: Liver resection remains the most effective method of treating liver tumors. Currently, the laparoscopic approach is considered the gold standard compared to the open approach; however, the emergence of robotic surgery offers a new minimally invasive approach option with apparently better re-sults. The objective of this systematic review is to assess the benefits of robotic hepatectomy versus laparo-scopic hepatectomy in the resection of liver tumors. Methodology: This systematic review will include comparative, cohort, case-control studies with prospec-tive or retrospective data collection. Study participants will be patients diagnosed with benign or malignant liver tumors, including children and adolescents, noncirrhotic or compensated cirrhotic, undergoing robotic hepatectomy and laparoscopic hepatectomy procedures. The primary outcome measures are: 1. Estimated blood loss during surgery, 2. Operative time, 3. Laparotomy conversion rate, 4. Intraoperative mortality rate, 5. Morbidity rate (postoperative complications), 6. Post-surgical hospital stay. Electronic searches will be conducted on PubMed, Medline, and ScienceDirect (2010 to present). The Cochrane study risk of bias as-sessment will be used. The mean differences (MD) and the 95 confidence intervals (CI) will be used as measures of the treatment effect. The evaluation of heterogeneity will be carried out by visual inspection of the funnel diagram. The evaluation of the quality of the evidence and 'Summary of findings' tables will be used by the GRADE test.


Subject(s)
Humans , Child , Adolescent , Adult , Robotic Surgical Procedures , Hepatectomy , Treatment Outcome , Laparoscopy , Liver Neoplasms
5.
Rev. baiana saúde pública ; 45(3,supl.n.esp): 130-140, 28 dec. 2021.
Article in Portuguese | LILACS | ID: biblio-1352343

ABSTRACT

O angiossarcoma primário hepático é o tumor mesenquimal mais comum do fígado, representando cerca de 2% das neoplasias malignas primárias do órgão. Esse raro tumor tem sintomas inespecíficos, evolução agressiva e diagnóstico usualmente tardio, com prognóstico reservado mesmo quando tratado. Este trabalho consiste em um relato de caso de um paciente do sexo masculino, de 44 anos, que foi encaminhado à emergência do Hospital Geral Roberto Santos para investigação de quadro de anemia grave sintomática, síndrome consumptiva e hepatoesplenomegalia. Durante investigação laboratorial, evidenciou-se anemia com provável componente microangiopático associado à anemia da doença crônica. As sorologias para doenças virais e baciloscopia do escarro foram negativas. Foram detectados em exames de imagem dois nódulos hepáticos de grandes dimensões, adenomegalias retroperitonais, esplenomegalia de grande monta, volumoso derrame pleural à direita, além de alterações do esqueleto axial e apendicular. Evoluiu com síndrome da lise tumoral após tratamento clínico com corticoterapia por suspeita de linfoma, com óbito. A biópsia guiada por uma tomografia realizada previamente teve como conclusão perfil imuno-histoquímico compatível com angiossarcoma hepático. O angiossarcoma é um raro tumor, de difícil diagnóstico e tratamento, com evolução agressiva e achados clínico-laboratoriais pouco elucidativos, devendo a hipótese desta doença ser considerada no diagnóstico diferencial das neoplasias hepáticas. As opções terapêuticas são limitadas. Relatos de casos como este são de suma importância para o aumento do grau de suspeição clínica e um diagnóstico mais precoce dessa entidade de costumeira evolução catastrófica.


Primary hepatic angiosarcoma is the most common mesenchymal tumor of the liver, representing about 2% of primary hepatic malignancies. This rare tumor has nonspecific symptoms, delayed diagnosis, and aggressive evolution, with a poor prognosis even when treated. This study reports the case of a 44-year-old male patient referred to the emergency department of the Hospital Geral Roberto Santos with symptomatic severe anemia, consumptive syndrome, and hepatosplenomegaly. Laboratory investigation indicated anemia with a probable microangiopathic component and chronic disease anemia. Serology tests for viral diseases returned negative results, as well as sputum smear microscopy for tuberculosis. Imaging exams revealed two large hepatic nodules, retroperitoneal adenomegaly, large splenomegaly, large pleural effusion in the right lung, and bone involvement. After clinical treatment with corticosteroids for suspected lymphoma, the patient evolved with tumor lysis syndrome and died. Tomography-guided liver biopsy was previously performed, indicating an immunohistochemical profile compatible with hepatic angiosarcoma ­ a rare tumor of difficult diagnosis and treatments due to its aggressive evolution and poor clinical and laboratory findings. Considering the nonspecificity of imaging exams, this disease should be considered in the differential diagnosis of liver neoplasms investigation. Case reports such as the one described in this study are important for increasing the degree of clinical suspicion and earlier diagnosis of this malignancy.


El angiosarcoma hepático primario es el tumor mesenquimatoso del hígado más común y representa el 2% de las neoplasias malignas primarias del hígado. Este raro tumor presenta una sintomatología inespecífica, diagnóstico tardío y evolución agresiva, con mal pronóstico incluso en tratamiento. Este es un reporte de caso de un hombre de 44 años de edad, que fue remitido al servicio de urgencias del Hospital Geral Roberto Santos para investigar anemia severa sintomática, síndrome de consunción y hepatoesplenomegalia. Durante la investigación de laboratorio, se evidenció anemia con un probable componente microangiopático asociado a anemia por enfermedad crónica. La serología para enfermedades virales resultó negativa, así como la microscopía de frotis de esputo para tuberculosis. Las imágenes revelaron dos grandes nódulos hepáticos, adenomegalia retroperitoneal, gran esplenomegalia, gran derrame pleural en el pulmón derecho, así como afectación del esqueleto axial y apendicular. El paciente evolucionó con síndrome de lisis tumoral tras el tratamiento clínico con corticoides por sospecha de linfoma, y no se resistió. Previamente se realizó biopsia hepática guiada por tomografía con perfil inmunohistoquímico compatible con angiosarcoma hepático. El angiosarcoma es un tumor raro, de difícil diagnóstico y tratamiento por su evolución agresiva y deficientes hallazgos clínicos y de laboratorio. Los exámenes por imágenes son inespecíficos y la posibilidad de esta enfermedad debe considerarse en el diagnóstico diferencial de la investigación de neoplasias hepáticas. Las opciones terapéuticas son limitadas. Reportes de casos como este son importantes para incrementar el grado de sospecha clínica y el diagnóstico precoz de este tipo de evolución catastrófica habitual.


Subject(s)
Humans , Male , Tumor Lysis Syndrome , Research Report , Anemia , Hemangiosarcoma , Liver , Liver Neoplasms
6.
Braz. j. biol ; 81(3): 714-718, July-Sept. 2021. tab
Article in English | LILACS | ID: biblio-1153405

ABSTRACT

Abstract Pathogenic strains of Escherichia coli may invade the subcutaneous tissue of poultry and cause cellulitis, whilst the pathogen may also cause lesions in internal organs such as the liver. Current paper co-relates Escherichia coli and virulence genes characteristic of Avian Pathogenic Escherichia coli (APEC) in broilers´ cellulitis and liver lesions. One hundred carcasses were retrieved from the production chain in an avian abattoir in the state of Bahia, Brazil, between August 2013 and January 2014, due to detection of cellulitis lesions. Cellulitis and liver samples were retrieved aseptically to quantify E. coli by Petrifilm™ count fast method (3M Company) (AOAC 998.8). Virulent genes iss and iutA were removed from E. coli isolates by Polymerase Chain Reaction (PCR). Escherichia coli was isolated from 82.0% of broilers removed from the production chain and the bacterium was concomitantly detected in cellulitis and liver lesions in 40.0% of broilers. E. coli counts ranged between 1.00 and 4.73 log CFU/g in liver lesions and between 2.00 and 9.00 log UFC/g in cellulitis lesions. Virulent genes iutA and iss were detected in 97.56% and 89.02% of E. coli isolates, respectively. Genotype analysis demonstrated the concomitant amplification of genes iutA and iss in 60.0% (n=40) of samples of cellulitis and liver lesions in which the simultaneous isolation of E. coli occurred. There was a positive and significant co-relationship (r=0.22; p<0.05) between the variables occurrence of E. coli isolated from liver samples and the occurrence of E. coli isolated from cellulitis lesions. There were also positive and significant co-relationships between populations of E. coli from liver isolates and cellulitis lesions (r=0.46; p<0.05) when E. coli isolated in the liver and in cellulitis lesions was detected. Since results showed a relationship between E. coli in cellulitis and liver lesions and possible systemic infection, the occurrence of cellulitis lesions as a criterion for total discarding of carcass may be suggested.


Resumo Cepas patogênicas de Escherichia coli podem invadir o tecido subcutâneo das aves e provocar celulite aviária e este patógeno pode provocar lesões nos órgãos internos, como o fígado. Desta forma, objetivou-se correlacionar a presença de Escherichia coli e os genes de virulência característicos de Escherichia coli Patogênica para Aves (APEC) nas lesões de celulite e nos fígados dos frangos. Entre agosto de 2013 a janeiro de 2014, foram retiradas 100 carcaças da linha de produção por apresentarem lesões de celulite em um matadouro avícola da Bahia (Brasil). Foram coletadas amostras de celulite e fígados de frango assepticamente para quantificação de E. coli pelo método rápido de contagem Petrifilm™ (3M Company) (AOAC 998.8). Em seguida foi realizada a pesquisa dos genes de virulência iss e iutA nos isolados de E. coli utilizando a Reação em Cadeia da Polimerase (PCR). Escherichia coli foi isolada em 82,00% das aves retiradas da linha de produção e a bactéria foi detectada concomitantemente nas lesões de celulite e fígado em 40,00% das aves. As contagens de E. coli variaram de 1,00 a 4,73 log UFC/g nos fígados e de 2,00 a 9,00 log UFC/g nas lesões de celulite. Os genes de virulência iutA e iss foram encontrados em 97,56% e 89,02% dos isolados de E. coli, respectivamente. A análise genotípica revelou a amplificação concomitante dos genes iutA e iss em 60,00% (n=40) das amostras de lesões de celulite e fígado nas quais houve o isolamento simultâneo de E. coli. Foi observada correlação positiva e significativa (r=0,22; p<0,05) entre as variáveis ocorrência de E. coli isolada das amostras dos fígados e ocorrência E. coli isolada das lesões de celulite e, nos casos em que foi detectada a ocorrência de E. coli isolada em fígado e lesões de celulite, correlações positivas e significativas também foram evidenciadas entre as populações de E. coli dos isolados dos fígados e das lesões de celulite, (r=0,46; p<0,05). Assim ficou evidenciada a relação entre E. coli presente nas lesões de celulite e no fígado e uma possível infecção sistêmica, desta forma, sugere-se que a presença de lesões de celulite seja utilizada como critério para o descarte total da carcaça.


Subject(s)
Animals , Poultry Diseases , Escherichia coli Infections/veterinary , Liver Neoplasms , Brazil , Cellulitis , Chickens , Escherichia coli/genetics
7.
Prensa méd. argent ; 107(6): 307-311, 20210000. fig
Article in Spanish | LILACS, BINACIS | ID: biblio-1359098

ABSTRACT

Objetivo: Presentar metodología diagnostica y resección atípica, con fines curativos de hepatocarcinoma. Caso clínico: Femenina de 82 años, con múltiples antecedentes entre el que se destaca, hepatitis a virus C de 15 años de evolución, que presenta por estudios complementarios alta sospecha de hepatocarcinoma, se realiza laparotomía exploradora con resección atípica de tumor en segmento 5 y 6 con radiofrecuencia quirúrgica y colecistectomía con colangiografía intraoperatoria. Cursa post operatorio sin complicaciones con alta sanatorial al 8vo dia. Conclusion: Hay que sospechar esta patología en pacientes con antecedentes de hepatopatía viral, plantear screening adecuado para un diagnóstico temprano y la mejor resolución adaptada a cada paciente. Dentro de las opciones terapéuticas encontramos la radiofrecuencia quirúrgica como una buena herramienta, con índice bajo de complicaciones


Objective: To present diagnostic methodology and atypical resection, for curative purposes of hepatocarcinoma. Clinical case: An 82-year-old female, with multiple history factors, among them, hepatitis C virus of 15 years of evolution, which presents high suspicion of hepatocarcinoma due to complementary studies, exploratory laparotomy is performed with atypical resection of tumor in segments 5 and 6 with surgical radiofrequency and cholecystectomy with intraoperative cholangiography. Post-operative course without complications with sanatorial discharge on the 8th day. Conclusion: This pathology must be suspected in patients with history of viral liver disease. We suggest an adequate screening for an early diagnosis and the best resolution adapted to each patient. Among the therapeutic options we find surgical radiofrequency as a good tool, with a low rate of complications


Subject(s)
Humans , Female , Aged, 80 and over , Cholecystectomy/rehabilitation , Incidence , Aftercare/methods , Evaluation Studies as Topic , Early Detection of Cancer/methods , Laparotomy , Liver Neoplasms/therapy
8.
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
9.
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
10.
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
11.
Article in Spanish | LILACS, BNUY, UY-BNMED | ID: biblio-1248722

ABSTRACT

La mitad de los pacientes con cáncer de origen colorrectal desarrollan metástasis hepáticas durante el curso de su enfermedad y de esas el 80% son irresecables. La resecabilidad se define no por la extensión de la hepatectomía, sino por la función del hígado remanente, por lo que para pacientes con ciertos factores favorables se pueden realizar técnicas de remodelación hepática para aumentar el volumen del hígado remanente para que este sea suficiente. La hepatectomía en dos tiempos se basa en procedimientos secuenciales que buscan tratar metástasis hepáticas colorrectales consideradas inicialmente irresecables, logrando la resección completa de las mismas dejando un remanente hepático funcionante suficiente, lo cual no sería posible en un solo acto quirúrgico. El objetivo de este trabajo es presentar el caso clínico de un paciente portador de metástasis hepáticas sincrónicas de origen colorrectal irresecables, que luego de una quimioterapia de conversión, con el fin de aumentar el futuro remanente hepático y evitar falla hepática postoperatoria y realizar una resección oncológica, fue sometido a una hepatectomía en dos tiempos, técnica utilizada con baja frecuencia en nuestro medio, destacando una evolución favorable, con marcadores tumorales en valores normales y sin evidencia imagenológica de recaída local ni sistémica.


Half of colorectal cancer patients develop liver metastases during the course of their disease, 80% of which are unresectable. Resectability is defined not by the extent of the hepatectomy, but by the function of the liver remnant. Therefore, for patients with certain factors, liver remodeling techniques can be performed to increase volume of the remaining liver so that it is sufficient. Two-stage hepatectomy is performed on colorectal liver metastases which are initially considered unresectable in one stage resection procedures, in which sequential procedures are performed in order to achieve complete resection and preserve a sufficient functioning liver remnant. The objective of this paper is to present the case of a patient with unresectable synchronous colorectal liver metastases, in which after conversion chemotherapy, in order to increase the future liver remnant, avoid postoperative liver failure and perform an oncological resection underwent a two-stage hepatectomy, a technique used with low frequency in our setting, highlighting a favorable evolution, with tumor markers in normal values and without imaging evidence of local or systemic relapse.


Metade dos pacientes com câncer colorretal desenvolve metástases hepáticas durante o curso da doença e, desses, 80% são irressecáveis. A ressecabilidade é definida não pela extensão da hepatectomia, mas pela função do fígado remanescente; portanto, para pacientes com certos fatores favoráveis, técnicas de remodelação hepática podem ser realizadas para aumentar o volume do fígado remanescente de forma que seja suficiente. A hepatectomia em dois estágios é baseada em procedimentos sequenciais que buscam tratar metástases hepáticas colorretais inicialmente consideradas irressecáveis, obtendo ressecção completa, deixando um remanescente hepático funcional suficiente, o que não seria possível em um único ato cirúrgico. O objetivo deste trabalho é apresentar o caso clínico de um paciente com metástases hepáticas sincrônicas irressecáveis ​​de origem colorretal, que após quimioterapia de conversão, com o objetivo de aumentar o futuro remanescente hepático e evitar insuficiência hepática pós-operatória e realizar uma ressecção oncológica, foi submetido a dois Hepatectomia em estágio, técnica utilizada com baixa frequência em nosso meio, evidenciando evolução favorável, com marcadores tumorais em valores normais e sem evidências de imagem de recidiva local ou sistêmica.


Subject(s)
Humans , Male , Aged , Chemotherapy, Adjuvant , Induction Chemotherapy , Hepatectomy/methods , Liver Neoplasms/surgery , Liver Neoplasms/drug therapy , Follow-Up Studies , Treatment Outcome , Capecitabine/therapeutic use , Bevacizumab/therapeutic use , Oxaliplatin/therapeutic use
12.
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
13.
Rev. cuba. cir ; 60(1): e1018, ene.-mar. 2021. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1289380

ABSTRACT

Introducción: Los hemangiomas hepáticos son lesiones no epiteliales que se observan con mucha frecuencia en piezas quirúrgicas resecadas por otras razones. Los hemangiomas que miden 10 cm o más, denominados "hemangiomas gigantes", pueden producir síntomas, como dolor y manifestaciones de un síndrome de reacción inflamatoria y coagulopatía. Los hemangiomas hepáticos son los tumores hepáticos primarios más frecuentes y están presentes en un 0,4-20 por ciento de la población general y es característico que se detecten de manera accidental durante la evaluación de síntomas abdominales inespecíficos. Objetivo: Presentar a una paciente portadora de un hemangioma gigante y características anatómicas peculiares intervenida quirúrgicamente con buenos resultados y evolución excelente. Caso clínico: Paciente de sexo femenino de 24 años de edad, portadora de un Hemangioma hepático gigante en segmento lateral, con variante anatómica vascular que dificultó la embolización y facilitó la cirugía. Se realizó una lobectomía hepática izquierda con una evolución clínica satisfactoria y sin complicaciones. Conclusiones: Las resecciones quirúrgicas de hemangiomas gigantes sintomáticos son una opción terapéutica segura y muy válida ante el fracaso de la embolización(AU)


Introduction: Hepatic hemangiomas are nonepithelial lesions much frequently observed in surgical specimens resected for other reasons. Hemangiomas ten centimeters or more, called "giant hemangiomas," can cause symptoms such as pain, as well as manifestations of an inflammatory reaction syndrome and coagulopathy. Hepatic hemangiomas are the commonest primary hepatic tumors, are present in 0.4-20 percent of the general population, and are typically accidentally detected during the evaluation of nonspecific abdominal symptoms. Objective: To present the case of a patient with a giant hemangioma and unusual anatomical characteristics, who underwent surgery with good outcome and excellent evolution. Clinical case: 24-year-old female patient with a giant hepatic hemangioma in the lateral segment, with a vascular anatomical variant that made embolization difficult and facilitated surgery. A left hepatic lobectomy was performed with satisfactory and uncomplicated clinical evolution. Conclusions: Surgical resections of symptomatic giant hemangiomas are a safe and very valid therapeutic option in case of embolization failure(AU)


Subject(s)
Humans , Female , Young Adult , Hemangioma/epidemiology , Hemangioma, Cavernous/diagnostic imaging , Laparotomy/methods , Liver Neoplasms/pathology
15.
Rev. cuba. cir ; 60(1): e1034, ene.-mar. 2021. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1289372

ABSTRACT

Introducción: La historia de la cirugía del hígado abarca 28 siglos, lo que ha permitido su evolución desde considerar al hígado como un órgano intocable hasta realizar hepatectomías complejas y trasplante hepático. Esta investigación representa el balance de 10 años en la actividad de un grupo de cirugía hepatobiliar. Objetivo: Caracterizar el tratamiento quirúrgico de los tumores hepáticos sólidos en el Centro de Investigaciones Médico-Quirúrgicas entre los años 2009 y 2019. Métodos: Se realizó un estudio de tipo observacional, descriptivo, longitudinal y retrospectivo en el que se analizaron 129 pacientes que fueron tributarios de tratamiento quirúrgico. Resultados: Los tumores malignos representaron el 73 por ciento del total, dentro de este grupo se destacan los metastásicos con 50 casos. La morbilidad de esta cirugía fue del 13 por ciento y la mortalidad operatoria del 2 por ciento. La causa de muerte identificada fue el shock séptico por peritonitis generalizada. Conclusiones: Los tumores malignos fueron los más frecuentes. Se presentó una baja morbilidad encontrándose el derrame pleural como la complicación más usual. Existe una mortalidad acorde a los valores reportados para este tipo de cirugía(AU)


Introduction: The history of liver surgery covers twenty-eight centuries, which has allowed its evolution from considering the liver as an untouchable organ to performing complex hepatectomies and hepatic transplantation. This research describes the ten years' balance in the activity developed by a hepatobiliary surgery team. Objective: To characterize the surgical management of solid hepatic tumors in the Center for Medical-Surgical Research between 2009 and 2019. Methods: An observational, descriptive, longitudinal and retrospective study was carried out, for which 129 patients who underwent surgical treatment were analyzed. Results: Malignant tumors accounted for 73 percent of the total; within this group, metastatic tumors stand out, accounting for fifty cases. Morbidity of this surgery type was 13 percent, while operative mortality was 2 percent. The cause of death identified was septic shock due to generalized peritonitis. Conclusions: Malignant tumors were the most frequent. There was low morbidity, with pleural effusion as the most common complication. Mortality is consistent with the values reported for this type of surgery(AU)


Subject(s)
Humans , Peritonitis/mortality , Shock, Septic/mortality , Liver Transplantation/methods , Hepatectomy/methods , Liver Neoplasms/epidemiology , Epidemiology, Descriptive , Retrospective Studies , Observational Studies as Topic
16.
Arch. argent. pediatr ; 119(1): e65-e69, feb. 2021. tab, ilus
Article in Spanish | LILACS, BINACIS | ID: biblio-1147269

ABSTRACT

El hemangioma hepático es el tumor benigno de hígado más frecuente. Puede ser congénito o infantil, con diferentes evoluciones y complicaciones. La evolución clínica es muy variable, desde pacientes asintomáticos hasta cuadros de gravedad con insuficiencia cardíaca, síndrome de Kasabach-Merritt o síndrome compartimental. El diagnóstico se basa en la historia clínica y los estudios por imágenes, especialmente, la ecografía y el examen doppler en manos experimentadas. Resulta fundamental el diagnóstico diferencial con otras lesiones hepáticas, sobre todo, el hepatoblastoma. En los pacientes sintomáticos, el propranolol surge como primera línea terapéutica con buenos resultados y baja frecuencia de efectos adversos. Se presenta el caso de un recién nacido con hemangioma hepático asociado a síndrome de Kasabach-Merritt, con excelente respuesta y tolerancia al propranolol


Hepatic hemangioma is the most common benign liver tumor. It can be congenital or infantile with different outcomes and complications. The clinical manifestation varies from asymptomatic to severe conditions with heart failure, Kasabach-Merritt syndrome or compartment syndrome. Diagnosis depends on medical history and imaging studies, especially ultrasound and Doppler examination in experienced hands. Differential diagnosis is essential with other hepatic lesions, mainly hepatoblastoma. In symptomatic patients, propranolol emerges as the first line treatment with good results and low frequency of adverse effects. We present the case of a newborn with a hepatic hemangioma and Kasabach-Merritt syndrome with an excellent response and tolerance to propranolol.


Subject(s)
Humans , Male , Infant, Newborn , Kasabach-Merritt Syndrome , Hemangioma/congenital , Prenatal Diagnosis , Propranolol/therapeutic use , Liver Neoplasms
17.
Braz. j. med. biol. res ; 54(9): e10390, 2021. graf
Article in English | LILACS | ID: biblio-1249337

ABSTRACT

Sorafenib (SOR) resistance is still a significant challenge for the effective treatment of hepatocellular carcinoma (HCC). The mechanism of sorafenib resistance remains unclear. Several microRNAs (miRNAs) have been identified as playing a role in impairing the sensitivity of tumor cells to treatment. We examined the mechanism behind the role of miR-92b in mediating sorafenib resistance in HCC cells. We detected that miR-92b expression was significantly upregulated in SOR-resistant HepG2/SOR cells compared to parental HepG2/WT cells. After transfection with miR-92b inhibitor, the proliferation of HepG2/SOR cells was remarkably weakened and rates of apoptosis significantly increased. PTEN was considered to be a functional target of miR-92b according to a luciferase reporter assay. Knockdown of PTEN significantly impaired the ability of miR-92b inhibitor on increasing sorafenib sensitivity of HepG2/SOR cells. Furthermore, we confirmed by western blotting and immunofluorescence that miR-92b can mediate sorafenib resistance by activating the PI3K/AKT/mTOR pathway in HCC cells by directly targeting PTEN. These findings further validate the mechanism of miR-92b in SOR resistance in HCC treatment.


Subject(s)
Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/drug therapy , Drug Resistance, Neoplasm , MicroRNAs/genetics , Sorafenib/pharmacology , Liver Neoplasms/genetics , Liver Neoplasms/drug therapy , Signal Transduction , Gene Expression Regulation, Neoplastic , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Cell Proliferation , PTEN Phosphohydrolase/genetics , TOR Serine-Threonine Kinases
18.
Braz. j. med. biol. res ; 54(7): e10213, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249312

ABSTRACT

Sevoflurane (SEVO) is widely applied as an anesthetic, which exerts antitumor capacity in various cancers, including hepatocellular carcinoma (HCC). Previous studies indicated that long non-coding RNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) was upregulated, while microRNA-29a-3p (miR-29a-3p) was downregulated in HCC. Thus, we aimed to explore the roles of KCNQ1OT1 and miR-29a-3p in HCC cells exposed to SEVO. Cell proliferation, apoptosis, migration, and invasion were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and transwell assays, respectively. The levels of genes were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Furthermore, the interaction between miR-29a-3p and KCNQ1OT1 or chromebox protein homolog 3 (CBX3) was predicted by Starbase or Targetscan, and then confirmed by dual-luciferase reporter assay. We found that the levels of KCNQ1OT1 and CBX3 were decreased, while miR-29a-3p was increased in SEVO-treated HCC cells. KCNQ1OT1 overexpression weakened the inhibitory effects of SEVO on HCC cell proliferation, apoptosis, migration, and invasion. Interestingly, KCNQ1OT1 bound to miR-29a-3p, and miR-29a-3p targeted CBX3. KCNQ1OT1 upregulated CBX3 level by repressing miR-29a-3p expression. Furthermore, KCNQ1OT1 exerted tumor promotion in HCC cells via suppressing miR-29a-3p to regulate CBX3 expression. Collectively, our findings demonstrated that KCNQ1OT1 regulated the antitumor effects of SEVO on HCC cells through modulating the miR-29a-3p/CBX3 axis, providing a theoretical basis for the treatment of HCC.


Subject(s)
Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/drug therapy , Potassium Channels, Voltage-Gated , MicroRNAs/genetics , Liver Neoplasms/genetics , Liver Neoplasms/drug therapy , Chromosomal Proteins, Non-Histone , RNA, Long Noncoding/genetics , Sevoflurane/pharmacology
19.
Braz. j. med. biol. res ; 54(4): e10273, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153542

ABSTRACT

Vascular invasion and systemic immune-inflammation index (SII) are risk factors for the prognosis of patients with hepatocellular carcinoma. At present, the correlation between the two is not clear. This meta-analysis explored the relationship between preoperative SII and vascular invasion in patients with hepatocellular carcinoma. According to the search formula, the Pubmed, Embase, Cochrane, Web of Science, and CNKI databases were searched for the relevant research until March 2020. After the quality evaluation of the included literature, the odds ratio (OR) and its corresponding 95% confidence interval (CI) were used as the effect measure. Stata 15. 0 software was used for statistical analysis. The meta-analysis eventually included seven retrospective cohort studies of 3583 patients with hepatocellular carcinoma. The results showed that the choice of SII cut-off value affects SII's efficiency in predicting the risk of vascular invasion. In the cohort of studies with appropriate SII cut-off value, the high SII preoperative group had a higher risk of vascular invasion (OR=2.62; 95%CI: 2.07-3.32; P=0.000) and microvascular invasion (OR=1.82; 95%CI: 1.01-3.25; P=0.045) than the low SII group. The tumor diameter (OR=2.88; 95%CI: 1.73-4. 80; P=0.000) of the high SII group was larger than that of the low SII group. There was no publication bias in this study (Begg's test, P=0.368). As a routine, cheap, and easily available index, SII can provide a certain reference value for clinicians to evaluate vascular invasion before operation.


Subject(s)
Humans , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Retrospective Studies , Risk Factors , Inflammation
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