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Aim To investigate whether salvianolic acid B ( Sal B) has inhibitory effect on hepatoma HuH- 7 cells and explore whether it works via Hippo/YAP signaling pathway. Methods HuH-7 cells were induced by TGF-β1 (9 pmol · L
摘要
Hepatitis C virus infection (HCV) is the foremost reason of progressive hepatic fibrosis and cirrhosis, with an elevated risk of hepatocellular carcinoma (HCC) development. Medicinal plants have been used for human health benefits for several years, but their therapeutic potential needs to be explored. The main objective of this study was to figure out the in vitro antiviral and anticancer characteristics of total crude protein of Iberis gibraltarica against HCV and HCC. Total crude protein of Iberis gibraltarica was isolated and quantified. The level of cytotoxicity was measured against the HepG2 cell line and it shows no significant cytotoxicity at the concentration of 504µg/ml. The anti-HCV effect was determined by absolute quantification via real time RT-PCR method and viral titer was reduced up to 66% in a dose dependent manner against the total protein of Iberis gibraltarica. The anticancer potential of Iberis gibraltarica was also examined through mRNA expression studies of AFP and GPC3 genes against the total protein of Iberis gibraltarica-treated HepG2 cells. The results show up to 90% of the down-regulation expression of AFP and GPC3. The obtained results indicate the therapeutic potential of total protein of Iberis gibraltarica against HCV and hepatocellular carcinoma in vitro.
A infecção pelo vírus da hepatite C (HCV) é a principal causa de fibrose hepática progressiva e cirrose, com risco elevado de desenvolvimento de carcinoma hepatocelular (HCC). As plantas medicinais vêm sendo utilizadas para benefícios à saúde humana há vários anos, mas seu potencial terapêutico precisa ser explorado. O principal objetivo deste estudo foi descobrir as características antivirais e anticancerígenas in vitro da proteína bruta total de Iberis gibraltarica contra HCV e HCC. A proteína bruta total de Iberis gibraltarica foi isolada e quantificada. O nível de citotoxicidade foi medido contra a linha celular HepG2 e não apresenta citotoxicidade significativa na concentração de 504µg/ml. O efeito anti-HCV foi determinado por quantificação absoluta através do método RT-PCR em tempo real e o título viral foi reduzido em até 66% de forma dose-dependente contra a proteína total de Iberis gibraltarica. O potencial anticancerígeno de Iberis gibraltarica também foi examinado através de estudos de expressão de mRNA dos genes AFP e GPC3 contra a proteína total de células HepG2 tratadas com Iberis gibraltarica. Os resultados mostram até 90% da expressão de regulação negativa de AFP e GPC3. Os resultados obtidos indicam o potencial terapêutico da proteína total de Iberis gibraltarica contra HCV e carcinoma hepatocelular in vitro.
Subject(s)
Plants, Medicinal , Therapeutics , Carcinoma, Hepatocellular/drug therapy , Liver Cirrhosis/drug therapy摘要
Annona muricata Linn. (Annonaceae) is a tropical plant with multiple beneficial health effects including anticancer properties. In breast cancer patients, overexpression of the HER2 oncoprotein corresponds to a poor prognosis, thus the main purpose of this study was to evaluate the cytotoxicity of ethanolic extracts from dried and fresh leaf of A. muricata on HER2+ breast cancer cells. MTT assays were performed and IC50 determined in HCC1954 (HER2+) cells, as well as in MCF7 (HER-) and peripheral blood mononuclear cells (PBMC) used as controls. Total polyphenol content evaluation and phytochemical screening were also performed. The cytotoxic effect of A. muricata extracts (125-1000 µg/mL) was dose-dependent and cell-type specific. The extracts exhibited higher cytotoxicity against HCC1954 than MCF7 cells, but weak toxicity against PBMC. This is the first report of the cytotoxic effect of A. muricata on HCC1954 cells, highlighting its potential for treating anti-estrogen-resistant breast cancers and low toxicity against PBMC.
Annona muricata Linn. (Annonaceae) es una planta tropical con múltiples efectos benéficos en la salud incluyendo propiedades antitumorales. En pacientes con cáncer de mama la sobreexpresión del oncogen HER2 corresponde a un mal pronóstico, por lo que el objetivo principal de este estudio fue evaluar la citotoxicidad de extractos etanólicos de hojas secas y frescas de A. muricata en células tumorales de mama HER2+. Se aplicaron pruebas de MTT y se determinaron IC50en células HCC1954 (HER2+); se utilizaron células MCF7 (HER-) y células mononucleares de sangre periférica (PBMC) como control. Se valoró también el contenido en polifenoles totales, y se realizó un tamizaje fitoquímico. El efecto citotóxico de los extractos de A. muricata (125-1000 µg/mL) fue dosis-dependiente y específico para cada tipo celular. Los extractos presentaron mayor actividad citotóxica contra HCC1954 en comparación con MCF7 y baja toxicidad contra PBMC. Este es el primer reporte del efecto citotóxico de A. muricata en HCC1954 y destaca su potencial terapéutico para tratamiento de cáncer de mama resistentes a antiestrógeno y baja citotoxicidad contra PBMC.
Subject(s)
Breast Neoplasms/prevention & control , Annona/chemistry , Antineoplastic Agents/therapeutic use , Plants, Medicinal , Breast Neoplasms/drug therapy , Cytotoxins/pharmacology摘要
Mitochondrial dynamics are a contraversal issue in hepatocellular carcinoma. The present study tries to illustrate the role of mitochondrial dynamics proteins (mitofusin-2 (Mfn2) and YME1L) in hepatocarcinogenesis. Five groups were used: the control group and three HCC groups (after 8, 16, and 24 weeks from DENA induction). The last group was treated with Sorafenib (SP) (10 mg/kg), via oral gavage for 4 weeks after cancer induction. This study revealed that Mfn-2 was downregulated and YME1l was overexpressed in different HCC groups. This dysregulation of mitochondrial dynamics proteins was associated with high hepatic levels of cyclin D1, MMP-9, and MDA and overexpression of ki67 as well as decreasing the hepatic expression of tissue inhibitor of matrix metalloproteinase-3 (Timp-3) and Bax. To confirm the possible role of Mfn2 and YME1L in HCC, we assessed the effect of sorafenib on these parameters and its related HCC characteristics. Sorafenib corrected the level of Mfn2 and YME1L and decreased tumor cell proliferation as well. We also elucidated that mitochondrial dynamics proteins (Mfn2 and YME1L) could be a good therapeutic target for HCC.
摘要
Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.
Subject(s)
Humans , Carcinoma, Hepatocellular/pathology , Cell Hypoxia , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Liver Neoplasms/pathology , Signal Transduction/genetics , tRNA Methyltransferases/metabolism摘要
Objective:To investigate the efficacy and safety of different transcatheter arterial chemoembolization(TACE)-based regimens in patients with unresectable hepatocellular carcinoma(uHCC)and explore the optimal timing for combining TACE with tyrosine kinase inhibit-ors(TKIs)and immune checkpoint inhibitors(ICIs).Methods:A retrospective analysis was conducted on data from 555 patients with uHCC who underwent TACE-based treatment between April 2016 and December 2021 in Nanfang Hospital,Southern Medical University.The pa-tients were assigned into the following four groups according to different treatment regimens:TACE group(n=317),TACE combined with TKIs group(TACE+TKIs,n=66),TACE combined with ICIs group(TACE+ICIs,n=33),and TACE combined with TKIs+ICIs group(TACE+TKIs+ICIs,n=139).Subgroup analysis was performed within the TACE+TKIs+ICIs group,with patients being assigned into"pre-TACE"and"post-TACE"groups based on the timing of the combination therapy.Univariate and multivariate Cox regression analyses were conducted to identify pro-gnostic factors influencing overall survival(OS).Results:The TACE+TKIs+ICIs group showed the longest OS(21.9 months,95%confidence in-terval[CI]:17.2-26.6,P=0.030)and progression-free survival(PFS)(8.3 months,95%CI:7.3-9.3,P=0.004)compared to those in the other three groups.In the subgroup analysis,the"post-TACE"group had longer OS than the"pre-TACE"group(26.8 months vs.19.2 months,P = 0.011).The objective response rate(ORR)was 32.8%,41.1%,42.4%,and 52.5%(P=0.001)and the disease control rate(DCR)was 59.6%,71.2%,69.7%,and 82.7%(P<0.001)in the TACE,TACE+TKIs,TACE+ICIs,and TACE+TKIs+ICIs groups,respectively.The adverse events were similar to those reported in previous studies.Cox regression analysis revealed that tumor number,extrahepatic metastasis,and treatment regimen were independent factors influencing OS in patients(all P<0.05).Conclusions:TKIs or ICIs can improve OS and PFS in patients with uHCC receiving TACE,and the combination of TKIs+ICIs with TACE achieves better beneficial outcomes.The greatest OS was observed when the combination therapy TKIs+ICIs was initiated within 3 months after the first TACE procedure.
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Liver diseases constitute a major healthcare burden globally, including acute hepatic injury resulted from acetaminophen overdose, ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Attainable treatment strategies for most liver diseases remain inadequate, highlighting the importance of substantial pathogenesis. The transient receptor potential (TRP) channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver. It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels. Here, we discuss recent findings revealing TRP functions across the fundamental pathological course from early hepatocellular injury caused by various insults, to inflammation, subsequent fibrosis and hepatoma. We also explore expression levels of TRPs in liver tissues of ALD, NAFLD and HCC patients from Gene Expression Omnibus (GEO) or The Cancer Genome Atlas (TCGA) database and survival analysis estimated by Kaplan-Meier Plotter. At last, we address the therapeutical potential and challenges by pharmacologically targeting TRPs to treat liver diseases. The aim is to provide a better understanding of the implications of TRP channels in liver diseases, contributing to the discovery of novel therapeutic targets and efficient drugs.
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Aim To investigate the molecular mechanisms of alcohol extracts of Euphorbia fischeriana steud. against hepatocellular carcinoma (HCC) through a combination of network pharmacology analysis and experimental validation. Methods The active ingredients and targets of alcohol extracts of Euphorbia fischeriana steud. were determined through TCMSP, Swiss ADME, Swiss Target Prediction database and references. The databases DisGeNET and GeneCards were employed to screen potential HCC-related genes. Venny platform, STRING platform and Cytoscape software were applied to construct active ingredient-target-disease and protein-protein interaction (PPI) network maps. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed using the DAVID database. To assess the effects of Euphorbia fischeriana steud. alcohol extracts on BEL-7402 cells, the proliferation and apoptosis were detected by CCK-8, EdU and flow cytometry assays, and the related protein levels of JAK2/STAT3 pathway were analyzed by Western blot. Additionally, H22 hepatocellular carcinoma mouse model was used to evaluate the in vivo efficacy of Euphorbia fischeriana steud. alcohol extracts. Results A total of 916 HCC targeted genes, 30 active ingredients containing the related 567 potential targeted genes, and 115 intersection targets of disease and compounds were obtained. KEGG enrichment analysis identified JAK2/STAT3 signaling as a critical pathway. In vitro experiments showed the alcohol extracts of Euphorbia fischeriana steud. could inhibit proliferation, promote apoptosis and suppress JAK2/STAT3 signaling pathway in a dose-dependent manner in BEL-7402 cells. In addition, the alcohol extracts of Euphorbia fischeriana steud., either alone or in combination with sorafenib, dramatically blocked tumor growth in in vivo tests. Conclusions Euphorbia fischeriana steud. alcohol extracts have anti-cancer effects in HCC, and the molecular mechanisms may be connected to the regulation of JAK2/STAT3 signaling pathway.
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Tripartite motif containing protein 7 (TRIM7), as a member of the E3 ubiquitin ligase TRIM family, plays an important regulatory role in immune regulation, metabolism and other physiological processes. The aberrant expression of TRIM7 is closely related to the development and progression of hepatocellular carcinoma (HCC) and it shows a complex regulatory role. However, the regulatory mechanism for the expression of TRIM7 in HCC remains unknown. In this study, multiple online databases were used to analyze the expression of TRIM7 in HCC and data indicated that TRIM7 expression was upregulated in HCC and correlated to poor prognosis. Subsequently, the transcription factor binding sites in the TRIM7 promoter region were analyzed using UCSC and JASPAR databases, and the results showed that TRIM7 promoter contains four SP1 binding sites. In this work, we demonstrated that SP1 could directly bind to its binding sites in TRIM7 promoter and positively regulate the transcriptional activity driven by the TRIM7 promoter using dual luciferase reporter experiments and the ChIP-PCR method. Moreover, our results also showed SP1 overexpression upregulated the expression of TRIM7 at both mRNA and protein levels (P<0. 01),and SP1 inhibitor, mithramycin A, could reverse the activated effect of SP1 on TRIM7 expression (P<0. 01). In conclusion, this study preliminarily reveals the regulatory mechanism of TRIM7 upregulation in HCC, which provides an important theoretical basis for further study of the gene function, early diagnosis and targeted therapy.
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A variety of full 2ʹ-F/OMe-modified siRNAs were designed and synthesized, and the activity against hepatocellular carcinoma Huh-7 and HepG2 cells was evaluated. K&A DNA/RNA H-8 synthesizer was used to synthesize siRNAs, and neutral cytidinyl lipid DNCA mixed with cationic lipid CLD were used to transfect siRNA. By RT-qPCR and CCK-8 assay, the target gene silence and the proliferation of Huh-7 and HepG2 cells were detected. The siRNAs loading into Ago2 protein was detected by RNA-binding protein immunoprecipitation. Drug uptake and cell apoptosis were detected by flow cytometry, and the expression of PLK1 protein was detected by Western blot. Partial full 2ʹ-F/OMe modified siRNAs, especial siPLK1A3, increased the uptake of Huh-7 cells, enhanced their binding to Ago2 and gene silencing activity, down-regulated PLK1 protein, as well as induced more Huh-7 cell apoptosis and proliferation inhibition activity. It provides important data for the development of novel siRNA modification patterns and anti-HCC formulations.
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@#[摘 要] 肝细胞癌（HCC）的发病率和病死率正在逐年增长，严重威胁人类的健康和生命。近年来，以PD-1/PD-L1抑制剂为代表的免疫治疗迅速发展，但对晚期HCC疗效有限。治疗中实时监测循环肿瘤细胞（CTC）PD-L1表达，是评估免疫治疗有效性的重要指标之一。本案例通过TumorFisher检测技术实时监测1例HCC患者免疫治疗前后总CTC数及PD-L1+ CTC个数，结合影像学和血清学检查结果进一步评估患者免疫治疗疗效。患者治疗前总CTC数为5个/2 mL，PD-L1+ CTC为5个/2 mL，PD-L1+ CTC/总CTC为100%。用PD-1/PD-L1抑制剂行3周期免疫治疗后，PD-L1+ CTC/总CTC逐渐降低，肿瘤缩小，血清AFP及PIVKA-Ⅱ逐渐下降，PD-L1+ CTC/总CTC变化与肿瘤标志物、MRI检查结果一致。PD-L1+ CTC/总CTC可作为HCC免疫治疗疗效评估的辅助指标。
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Being the most common solid malignant tumor in the digestive system and the third leading cause of cancer-related death worldwide， hepatocellular carcinoma （HCC） is characterized by insidious onset， early recurrence/metastasis and poor prognosis. With the advantages of targeted precision， high specificity， minimal drug resistance， remarkable therapeutic efficacy and fewer side effects， molecular targeted drugs have become the hotspot and focus of tumor therapy research in recent years. As more is learned about the mechanism and clinical efficacy， some molecular targeted drugs have been recommended by HCC treatment guidelines. This paper reviewed the mechanism of HCC targeted therapy， molecular targeted drugs， relevant therapeutic protocols and outcomes so as to provide reference and evidence for subsequent research.
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Liver cancer is the second leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) being the most common form of primary liver cancer. Glypican-3 (GPC3) is a cell membrane proteoglycan which is rarely expressed in normal adult tissues but is specifically upregulated in HCC, which makes GPC3 a reliable target for the diagnosis and treatment of HCC. The role of GPC3 in the regulation of cancer development through Wnt, YAP, hedgehog and other signaling pathways were reviewed in this article. GPC3-targeted therapies, such as monoclonal antibodies, bispecific antibodies, tumor vaccines, immunotoxins, CAR-T cells, and photosensitizer therapy were also summarized. These treatment methods offered promising approaches for HCC treatment and future treatment strategies for HCC based on GPC3 were prospected in this paper.
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The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr990 to enhance its activity. Mutation of SERCA2-Tyr990 disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca2+ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca2+ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr990 in HCC.
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Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.
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【Objective】 To investigate the cell death-inducing effect of methyl rosmarinate (MR) on human hepatoma Hep-3B and SK-Hep1 cells and their potential mechanisms. 【Methods】 The effects of MR on the viability of Hep-3B, SK-Hep1 and MIHA cells were determined by cell counting kit-8 (CCK-8) assay. The morphological changes of three kinds of cells treated with different concentrations of MR were observed by optical microscopy. EdU assay and flow cytometry were used to detect the proliferation and apoptosis of Hep-3B and SK-Hep1 cells. Transwell assay was used to study the effects of MR on the migration and invasion of Hep-3B and SK-Hep1 cells. Western blotting was used to evaluate the protein expression levels of apoptosis, EMT and Akt/mTOR signaling pathways. 【Results】 After treated with different concentrations of MR (0~200 μmol/L) for 48 h, Hep-3B and SK-Hep1 cells activities were significantly decreased in a concentration-dependent manner (P<0.01), while there was no significant effect on MIHA cell activity (P>0.05), and the IC50 of Hep-3B and SK-Hep1 cells were 102.5 and 99.3 μmol/L, respectively. MR treatment (0-150 μmol/L) significantly inhibited the proliferation of Hep-3B and SK-Hep1 cells (P<0.05), while cell detachment and shrinkage were observed by optical microscopy on the Hep-3B and SK-Hep1 cells, while the morphology of MIHA cells was not changed. Compared with the control group, MR (100, 150 μmol/L) induced apoptosis in Hep-3B and SK-Hep1 cells, the expression levels of the pro-apoptotic proteins Bax and cleaved PARP were significantly increased (P<0.05), while the expression level of the anti-apoptotic protein Bcl-2 was significantly decreased (P<0.05). MR (100, 150 μmol/L) also inhibited the migration and invasion of HCC cells, significantly increased the expression of E-cadherin and decreased the expression of N-cadherin and Vimentin compared with the control group (P<0.05). Finally, Western blotting results showed that the expressions of p-Akt and p-mTOR in Hep-3B and SK-Hep1 treated by MR were significantly reduced in a dose-dependent manner, suggesting that MR may play an anti-cancer role by inhibiting Akt/mTOR signaling pathway. 【Conclusion】 MR can promote apoptosis in Hep-3B and SK-Hep1 cells, which may be closely related to the inhibition of Akt/mTOR signaling pathway.
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Background: Hepatocellular carcinoma (HCC) is considered one of the foremost cancers worldwide. Although the hepatic resection of HCC has a high existence in the clinical scenarios, locoregional management is preferred owing to the preservation of hepatic parenchyma with lower morbidity and mortality. Dynamic contrast-enhanced MR with subtraction imaging improves the evaluation of managed HCC with easy detection of residual or recurrent viable lesions. Patients and methods: This study was designed in a retrospective pattern from December 2020 to December 2022. Forty patients were referred to our radiology department with solitary HCC, underwent therapeutic intervention, then underwent follow-up by dynamic MRI study. Results: Forty patients with solitary HCC were conducted during our study; all underwent locoregional therapy with follow-up by dynamic MRI with subtraction technique one month later. The subtraction image has a sensitivity of 100%, specificity of 100%, PPV of 100%, NPV of 100%, and 100% accuracy, compared to 90.91%, 77.78%, 83.33%, 87.5%, and 85% for conventional dynamic images, 45.45%, 100%, 100%, 60% and 70% for diffusion-weighted images. Analysis of those results exhibited a considerable additive value of the subtraction technique to the dynamic MRI to detect the response of HCC after management. Conclusions: Subtraction MRI is a pivotal tool to assess the interventional treatment of HCC, particularly in lesions having pre-contrast high signal intensity with distinguished radiologists' confidence
Subject(s)
Humans , Male , Female , Magnetic Resonance Imaging , Sensitivity and Specificity , Liver Neoplasms , Treatment Outcome , Diagnosis摘要
Background: Chronic HBV (CH) infection and its consequences including cirrhosis (C) and Hepatocellular Carcinoma (HCC) still represent a major Global health. The relationship between HCC and various mutations of HBx gene has been reported. In the present study, we aimed to determine the sequence variation of HBx gene in patients with Chronic HBV infection or C/HCC. Materials and Methods : In this cross-sectional study, 15 patients with HBV chronic infection and 13 with C/HCC were included. After viral DNA extraction using commercial kit HBX gene was amplified using an in-house nestedPCR. Then, bi-directional sequencing was performed on the PCR product. The data resulting from sequencing were aligned with reference HBV sequence to identify the mutations. Results : The mean age of CH and C/HCC groups was 38.23�.46 and 50.67�.22 years old, respectively. We found 43 and 20 Amino acid substitutions inside the region of 88�4 from HBx protein in CH and C/HCC groups, respectively. In addition, K130M+V131I mutation was found in 13.34% (2/15) and 30.7% (4/13) of patients in the CH and C/HCC groups, respectively (P=0.36). Furthermore, 10 deletion mutations were observed in both groups with no significant difference (P=0.8). Conclusion : The results of the present study indicated the relatively high frequency of Amino acid substitutions and deletion, especially in part of region 88-154 from HBx Protein in patients with CH and C/HCC. The findings should be considered in a larger population
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RESUMEN La presencia de tejido hepático ectópico es una situación inusual que se corresponde con alteraciones en la embriogénesis hepática. Suelen encontrarse de manera incidental y cobran particular importancia por su mayor potencial carcinogénico. El tratamiento de este tipo de patología es habitualmente quirúrgico. Se presenta el caso de una paciente femenina de 27 años que manifestó dolor torácico dorsal; por presentar además una formación evidenciable en la tomografía computarizada se decidió conducta quirúrgica. Asimismo se realiza una revisión bibliográfica del tema.
ABSTRACT Ectopic liver tissue is a rare finding due to aberrant migration of hepatic cells during embryonic development that is mostly found incidentally and has particular relevance because of its significant carcinogenic potential. Surgical management is usually indicated. We report the case of a 27-year-old female patient with thoracic back pain and a mass in the computed tomography scan who underwent surgery. A bibliographic review is also presented.
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SUMMARY OBJECTIVE: Hepatocellular carcinoma is the most common primary malignant liver tumor. Mitochondrial DNA copy number has been shown to be associated with various malignancies. However, there has not been any study on the absolute quantification of mtDNA copy number in hepatocellular carcinoma. The aim of this study was to develop a new method for absolute quantification of mtDNA copy number and to relatively quantify the variations in the mtDNA copy number in hepatocellular carcinoma patients in comparison with healthy individuals. METHODS: Venous blood samples were collected from both hepatocellular carcinoma patients (34) and healthy individuals (34). Circulating cell-free DNAs were isolated and the relative quantification of mtDNA copy number variation was determined using quantitative polymerase chain reaction and digital polymerase chain reaction. RESULTS: It was found that the relative mtDNA copy number was significantly decreased in hepatocellular carcinoma patients in comparison with the control group (p<0.05). The median (range) and average of relative mtDNA/β-actin gene of the patients were determined as 42.8 cp/μL (11.1-88.5) and 45.1 cp/μL, respectively, while the median (range) and average relative mtDNA/β-actin gene of the control group were determined as 102.8 cp/μL (55.1-291.8) and 138.7 cp/μL, respectively (p<0.05). When quantitative polymerase chain reaction and digital polymerase chain reaction were compared, mtDNA/β-actin gene copy number ratio of digital polymerase chain reaction results was found to be 1.76-fold more than that of quantitative polymerase chain reaction results. CONCLUSION: Circulating mtDNA copy number was decreased in hepatocellular carcinoma patients in comparison with healthy individuals, and we suggest that it can be used as a noninvasive biomarker for hepatocellular carcinoma diagnosis in the future.