Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 5.191
Filter
1.
Braz. j. biol ; 84: e250575, 2024. tab, graf
Article in English | 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 | 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.
Arq. Ciênc. Vet. Zool. UNIPAR (Online) ; 25(2): e8895, jul-dez. 2022. ilus
Article in Portuguese | LILACS, VETINDEX | ID: biblio-1399615

ABSTRACT

O hemangiossarcoma é uma neoplasia mesenquimal maligna agressiva com elevada taxa de morbidade e de mortalidade em cães e gatos; que se desenvolve mais frequentemente em baço, fígado, coração, ossos além de poder manifestar metástases regionais. O presente relato tem por objetivo descrever um caso de um canino diagnosticado com hemangiossarcoma hepático em lobo caudado submetido a uma lobectomia total. A técnica cirúrgica consistiu na utilização da sutura de guilhotina modificada na base do lobo acometido utilizando fio de polidioxanona e, com o auxílio de um bisturi elétrico unipolar, e respeitando o distanciamento de 0,5 cm da sutura, foi realizada a lobectomia. Após a remoção do lobo, foi fixada uma esponja hemostática de colágeno na região da incisão como forma de auxílio no controle hemorrágico. Foi indicado também a realização de tratamento quimioterápico adjuvante, entretanto o tutor do animal optou pela não realização da mesma. Ainda assim, o paciente do presente relato obteve uma boa resposta ao procedimento, e o tutor ficou muito satisfeito, relatando que houve uma grande melhora na qualidade de vida do animal e que ele não sentia mais dor, voltando a ter o seu comportamento habitual.(AU)


Hemangiosarcoma is an aggressive malignant mesenchymal neoplasm with a high rate of morbidity and mortality in dogs and cats; which develops more frequently in the spleen, liver, heart, bones, in addition to being able to manifest regional metastases. The present report aims to describe a case of a canine diagnosed with hepatic hemangiosarcoma in the caudate lobe submitted to a total lobectomy. The surgical technique consisted of using a modified guillotine suture at the base of the affected lobe using polydioxanone thread and, with the aid of a unipolar electric scalpel, and respecting the distance of 0.5 cm from the suture, lobectomy was performed. After removing the lobe, a hemostatic collagen sponge was fixed in the region of the incision as an aid in hemorrhagic control. Adjuvant chemotherapy treatment was also indicated, however the animal's tutor chose not to perform it. Even so, the patient in the present report had a good response to the procedure, and the tutor was very satisfied, reporting that there was a great improvement in the animal's quality of life and that he no longer felt pain, returning to his usual behavior.(AU)


El hemangiosarcoma es una neoplasia mesenquimatosa maligna agresiva con una alta tasa de morbilidad y mortalidad en perros y gatos; la cual se desarrolla con mayor frecuencia en bazo, hígado, corazón, huesos, además de poder manifestar metástasis regionales. El presente reporte tiene como objetivo describir un caso de un canino con diagnóstico de hemangiosarcoma hepático en el lóbulo caudado sometido a una lobectomía total. La técnica quirúrgica consistió en utilizar una sutura de guillotina modificada en la base del lóbulo afectado con hilo de polidioxanona y, con la ayuda de un bisturí eléctrico unipolar, y respetando la distancia de 0,5 cm de la sutura, se realizó la lobectomía. Después de retirar el lóbulo, se fijó una esponja hemostática de colágeno en la región de la incisión como ayuda para el control hemorrágico. También se indicó tratamiento de quimioterapia adyuvante, sin embargo el tutor del animal optó por no realizarlo. Aun así, el paciente del presente reporte tuvo una buena respuesta al procedimiento, y el tutor quedó muy satisfecho, informando que hubo una gran mejoría en la calidad de vida del animal y que ya no sintió dolor, volviendo a su comportamiento habitual.(AU)


Subject(s)
Animals , Female , Dogs , Anterior Temporal Lobectomy/methods , Hemangiosarcoma/surgery , Liver Neoplasms/surgery , Animal Welfare , Liver/surgery
4.
An. Fac. Cienc. Méd. (Asunción) ; 55(2): 82-87, 20220801.
Article in Spanish | LILACS | ID: biblio-1380442

ABSTRACT

El Sarcoma Embrionario Indiferenciado, como tumor primario hepático es una patología que se presenta en la edad pediátrica, en adultos los casos son raros y representan aproximadamente el 0.2% de los tumores hepáticos primarios. Es una patología sumamente agresiva cuya presentación clínica es inespecífica destacándose el dolor en epigastrio e hipocondrio derecho y, en algunos casos, masa palpable en esta región del abdomen, así como síntomas de afectación sistémica como fiebre y pérdida de peso. El tratamiento curativo consiste en la resección quirúrgica del tumor y, en casos de irresecabilidad o afectación extrahepática, se justifica considerar radioquimioterapia paliativa y asociarla o no a cirugía. Pero a pesar de todo, el pronóstico es sombrío con una sobrevida menor a un año, por lo que el diagnóstico temprano es esencial. Se presenta el primer caso registrado de Sarcoma Embrionario Indiferenciado Hepático del Adulto en Paraguay


The primary hepatic sarcoma is a pathology characteristic of pediatric age, in adults are rare and account for approximately 0.2% of primary tumors. It is an extremely aggressive pathology whose clinical presentation is non-specific, highlighting the pain in epigastrium and right hypochondrium and in some cases, palpable mass in this region of the abdomen, as well as symptoms of systemic involvement such as fever and weight loss. The main treatment consists of surgical removal of the tumor and in cases of unresectableness or extrahepatic involvement it is justified to consider paliative radiochemotherapy and associate it or not with surgery. However, the prognosis is bleak with a survival of less than one year, so early diagnosis is essential. We present here the first registered case of Adult Primary Hepatic Sarcoma in Paraguay


Subject(s)
Sarcoma , Liver Neoplasms , Adult
5.
Arch. argent. pediatr ; 120(4): e187-e191, Agosto 2022. ilus
Article in Spanish | LILACS, BINACIS | ID: biblio-1379154

ABSTRACT

El hemangioendotelioma epiteloide hepático (HEHE) es un tumor vascular raro de menor malignidad que el hemangiosarcoma. En los poco frecuentes casos unilobulares, puede indicarse hepatectomía parcial con riesgo de recurrencia agresiva; en enfermedad hepática extensa, incluso con compromiso extrahepático, el trasplante hepático ha resultado efectivo. Las metástasis son más frecuentes en pulmón,peritoneo, ganglios linfáticos, bazo y sistema nervioso. Se presenta el caso de un adolescente asintomático con HEHE con metástasis pulmonares y compromiso ganglionar abdominal que recibió trasplante hepático con evolución favorable.


Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor of less malignancy than hemangiosarcoma. In the rare unilobar cases, partial hepatectomy may be indicated with risk of aggressive recurrence; in extensive liver disease, even with extrahepatic involvement, liver transplantation has been performed successfully. Metastases are more common in the lung, peritoneum, lymph nodes, spleen, and nervous system. We present the case of an asymptomatic adolescent with HEHE with lung metastases and abdominal lymph node involvement who received a liver transplant with a favorable outcome.


Subject(s)
Humans , Male , Adolescent , Liver Transplantation , Hemangioendothelioma, Epithelioid/surgery , Hemangioendothelioma, Epithelioid/diagnosis , Hemangioendothelioma, Epithelioid/pathology , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Lung Neoplasms/surgery , Treatment Outcome
6.
Rev. colomb. gastroenterol ; 37(2): 163-172, Jan.-June 2022. tab, graf
Article in English, Spanish | LILACS | ID: biblio-1394945

ABSTRACT

Abstract Introduction: Hepatocellular carcinoma (HCC) is the most frequent malignant primary liver tumor globally. In 2018, it ranked sixth and represented the fourth cause of death from cancer; the five-year overall survival is 18 %. Most cases of HCC develop in patients with cirrhosis of any etiology, especially because of hepatitis B and C viruses, alcohol, and recently nonalcoholic steatohepatitis (NASH). Aim: To analyze the clinical characteristics, diagnostic methods, treatments, prognostic variables, and survival. Materials and methods: This retrospective descriptive study was conducted on a cohort of patients diagnosed with cirrhosis and treated between January 2011 and December 2020 at a health care center in Bogotá. The diagnosis of HCC was confirmed radiologically or by biopsy. We analyzed the information descriptively with absolute frequency measures in the case of categorical variables. For continuous variables, the information was summarized with measures of central tendency (mean or median) and their relevant measures of dispersion. Results: We included 152 patients diagnosed with HCC, with a mean age of 69.4 years; 51.3 % were men. The leading cause of HCC was nonalcoholic fatty liver disease (NAFLD), which accounted for almost a third of cases (32 %); other causes were alcohol (15 %) and hepatitis C virus (14 %). The median manifestation of the tumor was two nodules with a size close to 4 cm. Besides, 35 % of patients had a BCLC (Barcelona Clinic Liver Cancer) stage with curative options, and 25 % received curative treatment options. The first-line systemic therapy used in this cohort was sorafenib®, used in 35 patients (33.7 %). Survival curves showed that women, Child-Pugh class A, and BCLC stage 0 had higher median survival. Multivariate analysis showed a higher risk of death for males (hazard ratio [HR]: 2.16; confidence interval [CI]: 1.24-3.76), Child-Pugh class B (HR: 2.14; CI 1.16-3.95), and Child-Pugh class C (HR: 7.52; CI 2.88-19.57). Conclusions: NAFLD is the leading cause of HCC in this cohort. A third of patients are diagnosed in early BCLC stages with a curative treatment option, and 25 % are treated with curative therapies. Sorafenib was the first-line therapy in advanced HCC. Overall survival after diagnosis of HCC remains low, being necessary to join forces in the follow-up of patients with cirrhosis to improve these outcomes.


Resumen Introducción: el hepatocarcinoma (HCC) es el tumor hepático primario maligno más frecuente en el mundo: en 2018 ocupó la sexta posición y representó la cuarta causa de muerte por cáncer; la supervivencia global a 5 años es del 18 %. La mayoría de los casos de HCC se desarrolla en pacientes con cirrosis de cualquier etiología, especialmente por virus de la hepatitis B y C, alcohol y, recientemente, por la esteatohepatitis no alcohólica (NASH). Objetivo: analizar las características clínicas, métodos de diagnóstico, tratamientos, variables pronósticas y supervivencia. Metodología: estudio descriptivo retrospectivo de una cohorte de pacientes con diagnóstico de cirrosis atendidos entre enero de 2011 y diciembre de 2020 en un centro de atención médica de Bogotá, con diagnóstico de HCC confirmado radiológicamente o por biopsia. La información se analizó de forma descriptiva con medidas de frecuencia absoluta en el caso de las variables categóricas; para las variables continuas se resumió la información con medidas de tendencia central (media o medianas) y su respectiva medida de dispersión. Resultados: se incluyeron 152 pacientes diagnosticados con HCC, con edad promedio de 69,4 años, 51,3 % eran hombres. La principal causa de HCC fue el hígado graso no alcohólico (NAFLD), que representó casi una tercera parte de los casos (32 %); otras causas fueron el alcohol (15 %) y el virus de la hepatitis C (14 %). La mediana de presentación del tumor fue de 2 nódulos con un tamaño cercano a 4 cm. El 35 % de los pacientes tenía un estadio BCLC (Barcelona Clinic Liver Cancer) con opciones curativas y el 25 % de los pacientes recibió opciones curativas de tratamiento. La terapia sistémica de primera línea utilizada en esta cohorte fue el sorafenib®, que se utilizó en 35 pacientes (33,7 %). Las curvas de supervivencia mostraron que las mujeres, el estadio Child-Pugh A y el estadio BCLC 0 presentaron mayores medianas de supervivencia. El análisis multivariado evidenció un mayor riesgo de muerte al ser hombre (Hazard ratio [HR]: 2,16; intervalo de confianza [IC]: 1,24 a 3,76), estar en los estadios Child-Pugh B (HR: 2,14; IC: 1,16 a 3,95) y Child-Pugh C (HR: 7,52; IC: 2,88 a 19,57). Conclusiones: el NAFLD es la principal causa de HCC en la presente cohorte, una tercera parte de los pacientes se diagnostica en estadios BCLC tempranos con opción curativa de tratamiento, y un 25 % se trata con terapias curativas. El sorafenib fue la terapia de primera línea en HCC avanzado. La supervivencia global luego del diagnóstico de HCC sigue siendo baja, y es necesario aunar esfuerzos en el seguimiento de los pacientes con cirrosis para mejorar estos resultados.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Therapeutics , Hepatitis B virus , Carcinoma, Hepatocellular , Diagnosis , Non-alcoholic Fatty Liver Disease , Sorafenib , Hepatitis B , Liver Neoplasms , Patients , Survival , Confidence Intervals , Causality , Multivariate Analysis , Central Trend Measures , Neoplasms
7.
Rev. cir. (Impr.) ; 74(1): 112-119, feb. 2022. ilus
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1388911

ABSTRACT

Resumen El trasplante hepático con donante vivo (THDV) es un procedimiento complejo y desafiante para el cirujano, ya que exige garantizar tanto la máxima seguridad para el donante, así como también, la mejor calidad del injerto para el receptor. Debido a lo anterior, la implementación de la cirugía mini-invasiva ha sido lenta en esta área. Sin embargo, en los últimos 10 años, gracias a los avances que ha experimentado la cirugía hepática laparoscópica, ha aumentado el interés de algunos grupos altamente especializados por incorporar la cirugía mini-invasiva a la cirugía del donante, principalmente en trasplante hepático donante vivo adulto-pediátrico (THDVA-P). Los favorables resultados obtenidos en esta área incluso han llevado a los expertos en el tema, a categorizar el abordaje laparoscópico para la cirugía del donante como el procedimiento estándar en THDVA-P. Contrario a lo anterior, la implementación de la laparoscopía para trasplante hepático donante vivo adulto-adulto (THDVA-A), es más compleja y requiere en su mayoría, una hepatectomía de lóbulo derecho o izquierdo para cumplir con las necesidades volumétricas del receptor. Esta cirugía es de mayor dificultad y riesgo para el donante, por lo que su indicación por vía mini-invasiva está limitada a centros de alto volumen y preparación, tanto en laparoscopía, como en trasplante hepático. En este trabajo, se busca dar a conocer la técnica quirúrgica y nuestra experiencia inicial con la primera hepatectomía derecha totalmente laparoscópica (HDTL) para THDVA-A realizada en Chile.


Living donor liver transplantation is a complex and challenging procedure. The surgeon needs to guarantee maximum safety for the donor, as well as the best quality of the graft for the recipient. For this reason, the implementation of mini-invasive surgery has been slow in this area. However, in the last 10 years, due to the advances in laparoscopic liver surgery, the interest of some highly specialized groups has increased in incorporating mini-invasive surgery into donor surgery, mainly in pediatric living donor liver transplantation. The favorable results obtained in this field, have even led to turn this procedure, into the technique of choice for pediatric living donor liver transplantation. Nevertheless, this procedure is even more challenging for adult-to-adult living donor transplantation. To meet the volumetric criteria of an adult, a complete hepatectomy of right or left lobe is mostly required. This surgery is of greater complexity and risk for the donor, so its indication by minimally invasive approach is limited to high-volume centers with preparation, both in laparoscopy and liver transplants. In this report we seek to present our surgical technique and initial experience with the first pure laparoscopic right hepatectomy for adult-to-adult living donor liver transplantation carried out in Chile.


Subject(s)
Humans , Female , Adult , Laparoscopy , Living Donors , Liver Neoplasms/surgery , Tomography, X-Ray Computed/methods , Chile , Liver Transplantation/methods , Imaging, Three-Dimensional , Abdomen/diagnostic imaging , Hepatectomy
8.
Bol. latinoam. Caribe plantas med. aromát ; 21(1): 108-122, ene. 2022. ilus, tab
Article in English | LILACS | ID: biblio-1372494

ABSTRACT

Cota tinctoria is a medicinal plant which has been used for management of cancer in folk medicine of various regions. The aim of present study is to investigate cytotoxic activity of different concentrations of hydroalcoholic extract of C. tinctoria flowers on gastric (AGS) and liver (Hep-G2) cancer cell lines as well as Human Natural GUM fibroblast (HUGU) cells. Cell mortality rates were examined after 24, 48 and 72 h incubations using the MTT assay. IC50of extract on AGS cells after 24, 48 and 72h was 1.46, 1.29 and 1.14 µg/mL respectively. The extract demonstrated IC50 of 5.15, 3.92 and 2.89 µg/mL on Hep-G2 cells after 24, 48 and 72 h respectively. No cytotoxic effect was detected on HUGU (Human Natural GUM fibroblast) cells. C. tinctoria seems to have a promising potential to be considered as a source for anticancer drug discovery. However, more experimental and clinical studies are required.


Cota tinctoria es una planta medicinal que se ha utilizado para el tratamiento del cáncer en la medicina popular de varias regiones. El objetivo del presente estudio es investigar la actividad citotóxica de diferentes concentraciones de extracto hidroalcohólico de flores de C. tinctoria en líneas celulares de cáncer gástrico (AGS) e hígado (Hep-G2), así como en células de fibroblasto GUM humano natural (HUGU). Se examinaron las tasas de mortalidad celular después de incubaciones de 24, 48 y 72 h utilizando el ensayo MTT. La CI50 del extracto en células AGS después de 24, 48 y 72 h fue de 1,46; 1,29 y 1,14 µg respectivamente. El extracto demostró una CI50 de 5,15, 3,92 y 2,89 µg/mL en células Hep-G2 después de 24, 48 y 72 h, respectivamente. No se detectó ningún efecto citotóxico en las células HUGU (fibroblasto GUM humano natural). C. tinctoria parece tener un potencial prometedor para ser considerada como una fuente de descubrimiento de fármacos contra el cáncer. Sin embargo, se requieren más estudios experimentales y clínicos.


Subject(s)
Plant Extracts/administration & dosage , Asteraceae/chemistry , Cell Line, Tumor/drug effects , Liver Neoplasms/drug therapy , Antineoplastic Agents, Phytogenic/administration & dosage , Stomach Neoplasms/drug therapy , Flavonoids/analysis , Plant Extracts/pharmacology , Plant Extracts/chemistry , Cell Culture Techniques , Anthemis/chemistry , Phenolic Compounds/analysis , Hep G2 Cells/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry
9.
Article in Chinese | WPRIM | ID: wpr-941028

ABSTRACT

OBJECTIVE@#To explore the transcriptional regulation mechanism and biological function of low expression of vasoactive intestinal peptide receptor 1 (VIPR1) in hepatocellular carcinoma (HCC).@*METHODS@#We constructed plasmids carrying wild-type VIPR1 promoter or two mutant VIPR1 promoter sequences for transfection of the HCC cell lines Hep3B and Huh7, and examined the effect of AP-2α expression on VIPR1 promoter activity using dual-luciferase reporter assay. Pyrosequencing was performed to detect the changes in VIPR1 promoter methylation level in HCC cells treated with a DNA methyltransferase inhibitor (DAC). Chromatin immunoprecipitation was used to evaluate the binding ability of AP-2α to VIPR1 promoter. Western blotting was used to assess the effect of AP-2α knockdown on VIPR1 expression and examine the differential expression of VIPR1 in the two cell lines. The effects of VIPR1 overexpression and knockdown on the proliferation, cell cycle and apoptosis of HCC cells were analyzed using CCK8 assay and flow cytometry. We also observed the growth of HCC xenograft with lentivirus-mediated over-expression of VIPR1 in nude mice.@*RESULTS@#Compared with the wild-type VIPR1 promoter group, co-transfection with the vector carrying two promoter mutations and the AP-2α-over-expressing plasmid obviously restored the luciferase activity in HCC cells (P < 0.05). DAC treatment of the cells significantly decreased the methylation level of VIPR1 promoter and inhibited the binding of AP-2α to VIPR1 promoter (P < 0.01). The HCC cells with AP-2α knockdown showed increased VIPR1 expression, which was lower in Huh7 cells than in Hep3B cells. VIPR1 overexpression in HCC cells caused significant cell cycle arrest in G2/M phase (P < 0.01), promoted cell apoptosis (P < 0.001), and inhibited cell proliferation (P < 0.001), while VIPR1 knockdown produced the opposite effects. In the tumor-bearing nude mice, VIPR1 overexpression in the HCC cells significantly suppressed the increase of tumor volume (P < 0.001) and weight (P < 0.05).@*CONCLUSION@#VIPR1 promoter methylation in HCC promotes the binding of AP-2α and inhibits VIPR1 expression, while VIPR1 overexpression causes cell cycle arrest, promotes cell apoptosis, and inhibits cell proliferation and tumor growth.


Subject(s)
Animals , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/pathology , Luciferases/genetics , Methylation , Mice , Mice, Nude , Receptors, Vasoactive Intestinal Polypeptide, Type I/metabolism , Transcription Factor AP-2/metabolism
10.
Article in Chinese | WPRIM | ID: wpr-941009

ABSTRACT

OBJECTIVE@#To explore the marker genes correlated with the prognosis, progression and clinical diagnosis of hepatocellular carcinoma (HCC) based on bioinformatics methods.@*METHODS@#The TCGA-LIHC, GSE84432, GSE143233 and GSE63898 datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed. The differentially expressed genes (DEGs) shared by different disease types were obtained using GEO2R and edge R packages, and Gene Ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) enrichment analyses of the DEGs were performed. The expression levels of these DEGs in normal and cancerous tissues were verified in TCGA-LIHC to identify the upregulated genes in HCC. Survival analysis, receiver-operating characteristic (ROC) curve analysis, and correlation analysis between the key genes and the clinical features of the patients were carried out using the R language. The differential expressions of 15 key genes were verified in clinical samples of HCC and adjacent tissues using RT-qPCR.@*RESULTS@#A total of 118 common DEGs were obtained in the database, and among them two genes, namely ATPase Na +/K + transport subunit beta 3 (ATP1B3) and actin regulator (ENAH), showed increased expressions with disease progression. Survival analysis combined with the TCGA-LIHC dataset suggested that high expressions of ATP1B3 and ENAH were both significantly correlated with a poor prognosis of HCC patients (P < 0.05), and their AUC values were 0.821 and 0.933, respectively. A high expression of ATP1B3 was correlated with T stage, pathological stage and pathological grade of the tumors (P < 0.05), while that of ENAH was associated only with an advanced tumor grade (P < 0.05). The results of RT-qPCR showed that ATP1B3 and ENAH were both significantly upregulated in clinical HCC tissues (P < 0.05).@*CONCLUSION@#ATPIB3 and ENAH are both upregulated in HCC, and their high expressions may serve as biomarkers of progression of liver diseases and a poor prognosis of HCC.


Subject(s)
Carcinoma, Hepatocellular/pathology , Data Mining , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/pathology , Microfilament Proteins/metabolism , Sodium-Potassium-Exchanging ATPase/metabolism
11.
Article in Chinese | WPRIM | ID: wpr-941008

ABSTRACT

OBJECTIVE@#To explore the effective components of Yiqi Jiedu recipe and the main biological processes and signal pathways involved in the therapeutic mechanism of the recipe in treatment of primary liver cancer through network pharmacology and molecular docking approaches.@*METHODS@#TCMSP, Uniport, Genecards and String databases were searched to obtain the target genes of drugs and disease using Cytoscape 3.8.2 software. GO and KEGG enrichment analyses were performed to identify the common genes in the target genes of the drugs and disease. Using Pubcham, RCSB and Autoduck, the effective components of the drugs were connected with the final core genes. The effects of different concentrations of Yiqi Jiedu recipe on the expressions of the core genes DHX9, HNRNPK, NCL and PABPC1 in HepG2 cells were analyzed with Western blotting and real- time fluorescence quantitative PCR.@*RESULTS@#We finally identified 8 core genes from the drug and disease targets, including DDX5, HNRNPK, PABPC1, DHX9, RPS3A, RPS3, RPL13, and NCL. GO analysis showed that these core genes were involved mainly in the biological processes of adrenaline receptor signal communication, movement of cellular or subcellular components, blood particles, adhesion class and iron ion binding. KEGG analysis showed that the Ras signaling pathway had the greatest gene enrichment. The results of molecular docking suggested that the effective components of the recipe were capable of docking with the core genes under natural conditions, and PABPC1 and stigmasterol had the highest binding energy. In HepG2 cells, treatment with 10% medicated serum for 48 h had the strongest effect on the expression of DHX9, HNRNPK, NCL and PABPC1 (P < 0.05).@*CONCLUSION@#Yiqi Jiedu recipe is capable of regulating viral expression of primary liver cancer multiple effective components that bind to DHX9, HNRNPK, NCL and PABPC1.


Subject(s)
DEAD-box RNA Helicases , Drugs, Chinese Herbal/therapeutic use , Humans , Liver Neoplasms/drug therapy , Molecular Docking Simulation , Neoplasm Proteins , Network Pharmacology , Ribosomal Proteins , Signal Transduction
12.
Frontiers of Medicine ; (4): 467-482, 2022.
Article in English | WPRIM | ID: wpr-939878

ABSTRACT

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.


Subject(s)
Anilides/pharmacology , Animals , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Cell Proliferation , Endothelial Cells/metabolism , Humans , Liver Neoplasms/drug therapy , Pyridines/pharmacology , Sirolimus/pharmacology , Xenograft Model Antitumor Assays
13.
Article in English | WPRIM | ID: wpr-939776

ABSTRACT

OBJECTIVE@#To identify specific Chinese medicines (CM) that may benefit patients with primary liver cancer (PLC), and to explore the mechanism of action of these medicines.@*METHODS@#In this retrospective, singlecenter study, prescription information from PLC patients was used in combination with Traditional Chinese Medicine Inheritance Supports System to identify the specific core drugs. A system pharmacology approach was employed to explore the mechanism of action of these medicines.@*RESULTS@#Taking CM more than 6 months was significantly associated with improved survival outcomes. In total, 77 putative targets and 116 bioactive ingredients of the core drugs were identified and included in the analysis (P<0.05). A total of 1,036 gene ontology terms were found to be enriched in PLC. A total of 75 pathways identified from Kyoto Encyclopedia of Genes and Genomes were also enriched in this disease, including fluid shear stress, interleukin-17 signaling, signaling between advanced glycan end products and their receptors, cellular senescence, tumor necrosis factor signaling, p53 signaling, cell cycle signaling, steroid hormone biosynthesis, T-helper 17 cell differentiation, and metabolism of xenobiotics by cytochrome. Docking studies suggested that the ingredients in the core drugs exert therapeutic effects in PLC by modulating c-Jun and interleukin-6.@*CONCLUSIONS@#Receiving CM for 6 months or more improves survival for the patients with PLC. The core drugs that really benefit for PLC patients likely regulates the tumor microenvironment and tumor itself.


Subject(s)
Data Mining , Drugs, Chinese Herbal/therapeutic use , Humans , Liver Neoplasms/drug therapy , Medicine, Chinese Traditional , Network Pharmacology , Retrospective Studies , Tumor Microenvironment
14.
Article in English | WPRIM | ID: wpr-939601

ABSTRACT

Objective@#To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( PPP2R3A) and hexokinase 1 ( HK1) in glycolysis of hepatocellular carcinoma (HCC).@*Methods@#In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A-related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1. Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A.@*Results@#RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1. PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells.@*Conclusion@#Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer.


Subject(s)
Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glycolysis , Hexokinase/metabolism , Humans , Liver Neoplasms/pathology , Protein Phosphatase 2/metabolism , RNA, Small Interfering/metabolism
15.
Article in Chinese | WPRIM | ID: wpr-936046

ABSTRACT

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/therapeutic use , Case-Control Studies , Colorectal Neoplasms/drug therapy , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Liver Neoplasms/drug therapy , Prognosis , Retrospective Studies
16.
Chinese Journal of Hepatology ; (12): 443-446, 2022.
Article in Chinese | WPRIM | ID: wpr-935964

ABSTRACT

Artificial intelligence (AI) refers to the use of computer programs to simulate and extend human intelligence, and has application prospects in the diagnosis and treatment of diseases. This review focuses on the research status of the screening and diagnosis of NAFLD and nonalcoholic steatohepatitis using artificial intelligence technology, electronic health record data, multi-omics prediction models, image recognition technology based on liver imaging and pathological biopsy, and new drugs research and development, with a view to provide new ideas for the diagnosis and treatment.


Subject(s)
Artificial Intelligence , Biopsy/methods , Humans , Liver/pathology , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Non-alcoholic Fatty Liver Disease/pathology
17.
Chinese Journal of Hepatology ; (12): 340-344, 2022.
Article in Chinese | WPRIM | ID: wpr-935950

ABSTRACT

Transcatheter arterial chemoembolization (TACE) is the most commonly used method for non-surgical treatment of liver cancer, and it is usually used as an adjuvant therapy in patients who have not developed intrahepatic metastases after surgical resection. Postoperative adjuvant TACE therapy may provide a prognostic benefit in liver cancer patients with high recurrence risk. This article reviews the research progress of adjuvant TACE therapy for liver cancer after radical resection.


Subject(s)
Carcinoma, Hepatocellular/pathology , Chemoembolization, Therapeutic/methods , Hepatectomy , Humans , Liver Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Retrospective Studies
18.
Chinese Journal of Hepatology ; (12): 213-219, 2022.
Article in Chinese | WPRIM | ID: wpr-935929

ABSTRACT

Objective: To investigate the effects of glucose-6-phosphatase catalytic subunit (G6PC) recombinant adenovirus on proliferation and cell cycle regulation of liver cancer cells. Methods: Recombinant adenovirus AdG6PC was constructed. Huh7 cells and SK-Hep1 cells were set as Mock, AdGFP and AdG6PC group. Cell proliferation and clone formation assay were used to observe the proliferation of liver cancer cells. Transwell and scratch assay were used to observe the invasion and migration of liver cancer cells. Cell cycle flow cytometry assay was used to analyze the effect of G6PC overexpression on the proliferation cycle of liver cancer cells. Western blot was used to detect the effect of G6PC overexpression on the cell-cycle protein expression in liver cancer cells. Results: The recombinant adenovirus AdG6PC was successfully constructed. Huh7 and SK-Hep1 cells proliferation assay showed that the number of proliferating cells in the AdG6PC group was significantly lower than the other two groups (P < 0.05). Clone formation assay showed that the number of clones was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression could significantly inhibit the proliferation of liver cancer cells. Transwell assay showed that the number of cell migration was significantly lower in AdG6PC than the other two groups (P < 0.05). Scratch repair rate was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression can significantly inhibit the invasion and migration of liver cancer cells. Cell cycle flow cytometry showed that G6PC overexpression had significantly inhibited the Huh7 cells G(1)/S phase transition. Western blot result showed that G6PC overexpression had down-regulated the proliferation in cell-cycle related proteins expression. Conclusion: G6PC inhibits the proliferation, cell-cycle related expression, and migration of liver cancer cells by inhibiting the G(1)/S phase transition.


Subject(s)
Catalytic Domain , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glucose-6-Phosphatase/metabolism , Humans , Liver Neoplasms/genetics
19.
Chinese Journal of Hepatology ; (12): 117-120, 2022.
Article in Chinese | WPRIM | ID: wpr-935921

ABSTRACT

Primary hepatocellular carcinoma is one of the most common high-grade malignant tumors in the world. Its incidence ranks fifth among malignant tumors in China, and various therapeutic measures have poor curative effect. Pyruvate kinase type M2 is a key enzyme in the glycolytic pathway, and its abnormal expression in liver cancer is closely related to the proliferation, metastasis, diagnosis, treatment, prognosis, as well as drug and radiation resistance. Therefore, multi-pathway targeted regulation of pyruvate kinase type M2 use is expected to become a new direction for the treatment of primary liver cancer.


Subject(s)
Carcinoma, Hepatocellular , China , Humans , Liver Neoplasms , Prognosis , Pyruvate Kinase
20.
Chinese Journal of Hepatology ; (12): 103-106, 2022.
Article in Chinese | WPRIM | ID: wpr-935917

ABSTRACT

Hepatitis C virus (HCV) RNA can be cleared from the blood circulation by direct antiviral treatment to achieve sustained virologic response (SVR). Studies have shown that SVR after direct antiviral therapy can reduce the incidence of hepatocellular carcinoma; however, monitoring for hepatocellular carcinoma is still needed. This review briefly summarizes and discusses the existing studies on the possible causes of hepatitis C secondary to HCC after antiviral therapy, which is mainly divided into epigenetic alterations and abnormal DNA methylation, HCV-related cirrhosis and abnormal DNA amplification, HBV reactivation, several aspects of occult HCV infection, and the effect of direct antiviral treatment on hepatocellular carcinoma recurrence. In few cases, direct antiviral treatment cannot completely prevent the occurrence and recurrence of hepatitis C-related hepatocellular carcinoma. Therefore, its mechanism needs to be studied and explored, and clinicians should also approach it with caution.


Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Humans , Liver Neoplasms/etiology , Sustained Virologic Response
SELECTION OF CITATIONS
SEARCH DETAIL