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1.
Thorac Cancer ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32162769

RESUMO

BACKGROUND: To develop a model of malignant risk prediction of solitary pulmonary nodules (SPNs) using metabolic characteristics of lesions. METHODS: A total of 362 patients who underwent PET/CT imaging from January 2013 to July 2017 were analyzed. Differences in the clinical and imaging characteristics were analyzed between patients with benign SPNs and those with malignant SPNs. Risk factors were screened by multivariate nonconditional logistic regression analysis. The self-verification of the model was performed by receiver operating characteristic (ROC) curve analysis, and out-of-group verification was performed by k-fold cross-validation. RESULTS: There were statistically significant differences in age, maximum standardized uptake value (SUVmax ), size, lobulation, spiculation, pleural traction, vessel connection, calcification, presence of vacuoles, and emphysema between patients with benign nodules and those with malignant nodules (all P < 0.05). The risk factors for malignant nodules included age, SUVmax , size, lobulation, calcification and vacuoles. The logistic regression model was as follows: P = l/(1 + e-x ), x = - 5.583 + 0.039 × age + 0.477 × SUVmax + 0.139 × size + 1.537 × lobulation - 1.532 × calcification + 1.113 × vacuole. The estimated area under the curve (AUC) for the model was 0.915 (95% CI: 0.883-0.947), the sensitivity was 89.7%, and the specificity was 78.9%. K-fold cross-validation showed that the training accuracy was 0.899 ± 0.011, and the predictive accuracy was 0.873 ± 0.053. CONCLUSIONS: The risk factors for malignant nodules included age, SUVmax , size, lobulation, calcification and vacuoles. After verification, the model has satisfactory accuracy, and it may assist clinics make appropriate treatment decisions.

2.
Expert Opin Ther Targets ; 24(4): 389-402, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32106726

RESUMO

Objectives: Cepharanthine exhibits a wide range of therapeutic effects against numerous cancers by virtue of its pleiotropic mechanisms. However, cepharanthine monotherapy has insufficient drug efficacy for cancers in animal models and clinical trials. The mechanism of its limited efficacy is unknown.Methods: We investigated the possible mechanism for the limited drug efficacy of cepharanthine in cancer therapy using both hepatocellular carcinoma (HCC) primary cells and cell lines, in vitro and in mouse xenograft models.Results: We found that cepharanthine hydrochloride (CH), a semi-synthetic derivative of cepharanthine, induced mitophagy independent of mTOR signaling, and played an AMPK-dependent protective role in the cell fate of HCC in vitro and in vivo. Mechanistically, we demonstrated that CH may bind to GPR30 receptor to activate the subsequent signal cascade involving mitochondrial fission, thus facilitating mitophagy. Therefore, we proposed a new therapeutic regimen for HCC involving CH combined with an autophagy inhibitor. This regimen exhibited remarkable anti-cancer effects in HCC xenograft mouse model.Conclusion: These results identify CH as a new mitophagy inducer targeting GPR30 receptor. The combination therapy of CH and an autophagy inhibitor may become a novel strategy for enhancing the anti-tumor potential of cepharanthine in HCC.

3.
Breast Cancer Res Treat ; 180(2): 379-384, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32034579

RESUMO

PURPOSE: Protease-activated receptor 1 (PAR1) is a signaling protein ubiquitously present on the surface of tumor cells, and its homologous protein fragment, PAR1-activating peptide (P1AP), can inhibit protein signal transduction of PAR1/G in tumor cells. pH (Low) insertion peptide (pHLIP) can target the acidic tumor microenvironment (TME) and can be used as an excellent carrier to deliver P1AP to tumor cells for therapeutic purposes. METHODS: PAR1 expression on the surface of MDA-MB-231 cells and human MCF10A mammary epithelial cells was observed. The binding between fluorescent-labeled pHLIP(Var7)-P1AP and MDA-MB-231 cells under different pH values was analyzed. The effect of pHLIP(Var7)-P1AP on the proliferation of MDA-MB-231 cells was analyzed under the conditions of pH 7.4 and 6.0. RESULTS: PAR1 was highly expressed on the surface of MDA-MB-231 cells. In an acidic environment (pH 6.0 and 5.0), fluorescent-labeled pHLIP(Var7)-P1AP and MDA-MB-231 cells had a high binding ability, and the binding ability increased with the decrease in pH. In an acidic environment (pH 6.0), pHLIP(Var7)-P1AP significantly inhibited MDA-MB-231 cell proliferation. With 0.5 µg, 1 µg, 2 µg, 4 µg, and 8 µg of pHLIP(Var7)-P1AP, the cell proliferation inhibition rates were 3.39%, 5.27%, 14.29%, 22.14%, and 35.69%, respectively. CONCLUSION: PAR1 was highly expressed on the surface of MDA-MB-231 cells. pHLIP(Var7)-P1AP can effectively target MDA-MB-231 cells in an acidic environment and inhibit the growth of MDA-MB-231 cells by inhibiting the signal transduction of PAR1/G protein.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31912582

RESUMO

Sulfur is not normally considered a light-emitting material, even though there have been reports of a dim luminescence of this compound in the blue-to-green spectral region. Now, it is shown how to make red-emissive sulfur by a two-step oxidation approach using elemental sulfur and Na2 S as starting materials, with a high photoluminescence quantum yield of 7.2 %. Polysulfide is formed first and is partially transformed into Na2 S2 O3 in the first step, and then turns back to elemental S in the second step. The elevated temperature and relatively oxygen-deficient environment during the second step transforms Na2 S2 O3 into Na2 SO3 incorporated with oxygen vacancies, thus resulting in the formation of a solid-state powder consisting of elemental S embedded in Na2 SO3 . It shows aggregation-induced emission properties, attributed to the influence of oxygen vacancies on the emission dynamics of sulfur by providing additional lower energy states that facilitate the radiative relaxation of excitons.

5.
Eur Radiol ; 30(2): 1274-1284, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31506816

RESUMO

OBJECTIVES: To develop and validate a radiomics nomogram for preoperative differentiating renal angiomyolipoma without visible fat (AML.wovf) from homogeneous clear cell renal cell carcinoma (hm-ccRCC). METHODS: Ninety-nine patients with AML.wovf (n = 36) and hm-ccRCC (n = 63) were divided into a training set (n = 80) and a validation set (n = 19). Radiomics features were extracted from corticomedullary phase and nephrographic phase CT images. A radiomics signature was constructed and a radiomics score (Rad-score) was calculated. Demographics and CT findings were assessed to build a clinical factors model. Combined with the Rad-score and independent clinical factors, a radiomics nomogram was constructed. Nomogram performance was assessed with respect to calibration, discrimination, and clinical usefulness. RESULTS: Fourteen features were used to build the radiomics signature. The radiomics signature showed good discrimination in the training set (AUC [area under the curve], 0.879; 95%; confidence interval [CI], 0.793-0.966) and the validation set (AUC, 0.846; 95% CI, 0.643-1.000). The radiomics nomogram showed good calibration and discrimination in the training set (AUC, 0.896; 95% CI, 0.810-0.983) and the validation set (AUC, 0.949; 95% CI, 0.856-1.000) and showed better discrimination capability (p < 0.05) compared with the clinical factor model (AUC, 0.788; 95% CI, 0.683-0.893) in the training set. Decision curve analysis demonstrated the nomogram outperformed the clinical factors model and radiomics signature in terms of clinical usefulness. CONCLUSIONS: The CT-based radiomics nomogram, a noninvasive preoperative prediction tool that incorporates the Rad-score and clinical factors, shows favorable predictive efficacy for differentiating AML.wovf from hm-ccRCC, which might assist clinicians in tailoring precise therapy. KEY POINTS: • Differential diagnosis between AML.wovf and hm-ccRCC is rather difficult by conventional imaging modalities. • A radiomics nomogram integrated with the radiomics signature, demographics, and CT findings facilitates differentiation of AML.wovf from hm-ccRCC with improved diagnostic efficacy. • The CT-based radiomics nomogram might spare unnecessary surgery for AML.wovf.

6.
Mikrochim Acta ; 187(1): 38, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823079

RESUMO

Luminescent copper nanoclusters (Cu NCs) are chosen to functionalize Ti3C2Tx MXene flakes to form a new kind of nanohybrid. It was applied to the determination of glutathione (GSH) via photoluminescence (PL). The Cu NCs and MXene flakes are in close contact, and the blue PL of the Cu NCs (with excitation/emission peaks at 380/425 nm) is quenched. The addition of GSH triggers the separation of the nanohybrid. This results in the recovery of PL. GSH also promotes the PL of Cu NCs via host-guest interactions. Thus, target recognition, corresponding signal output and further magnification are accomplished in a single step. Under optimum conditions, the nanohybrid can detect GSH in the 5.0 to 100 µM concentration range and with a 3.0 µM detection limit. The assay is very specific and shows high selectivity towards metal ions, small biomolecules, amino acids, and thiol containing molecules. Graphical abstractLuminescent copper nanoclusters are used to functionalize Ti3C2Tx MXene flakes, forming a nanohybrid, which is applied to detect glutathione. Target recognition, signal output and magnification are accomplished in a single step, resulting in high selectivity.

7.
BMC Genomics ; 20(1): 825, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703618

RESUMO

BACKGROUND: 5-Azacytidine (5-azaC) promotes the development of 'Kyoho' grape berry but the associated changes in gene expression have not been reported. In this study, we performed transcriptome analysis of grape berry at five developmental stages after 5-azaC treatment to elucidate the gene expression networks controlling berry ripening. RESULTS: The expression patterns of most genes across the time series were similar between the 5-azaC treatment and control groups. The number of differentially expressed genes (DEGs) at a given developmental stage ranged from 9 (A3_C3) to 690 (A5_C5). The results indicated that 5-azaC treatment had not very great influences on the expressions of most genes. Functional annotation of the DEGs revealed that they were mainly related to fruit softening, photosynthesis, protein phosphorylation, and heat stress. Eight modules showed high correlation with specific developmental stages and hub genes such as PEROXIDASE 4, CAFFEIC ACID 3-O-METHYLTRANSFERASE 1, and HISTONE-LYSINE N-METHYLTRANSFERASE EZA1 were identified by weighted gene correlation network analysis. CONCLUSIONS: 5-AzaC treatment alters the transcriptional profile of grape berry at different stages of development, which may involve changes in DNA methylation.

8.
Mol Imaging ; 18: 1536012119883161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31625454

RESUMO

OBJECTIVE: To evaluate the value of 2-dimensional (2D) and 3-dimensional (3D) computed tomography texture analysis (CTTA) models in distinguishing fat-poor angiomyolipoma (fpAML) from chromophobe renal cell carcinoma (chRCC). METHODS: We retrospectively enrolled 32 fpAMLs and 24 chRCCs. Texture features were extracted from 2D and 3D regions of interest in triphasic CT images. The 2D and 3D CTTA models were constructed with the least absolute shrinkage and selection operator algorithm and texture scores were calculated. The diagnostic performance of the 2D and 3D CTTA models was evaluated with respect to calibration, discrimination, and clinical usefulness. RESULTS: Of the 177 and 183 texture features extracted from 2D and 3D regions of interest, respectively, 5 2D features and 8 3D features were selected to build 2D and 3D CTTA models. The 2D CTTA model (area under the curve [AUC], 0.811; 95% confidence interval [CI], 0.695-0.927) and the 3D CTTA model (AUC, 0.915; 95% CI, 0.838-0.993) showed good discrimination and calibration (P > .05). There was no significant difference in AUC between the 2 models (P = .093). Decision curve analysis showed the 3D model outperformed the 2D model in terms of clinical usefulness. CONCLUSIONS: The CTTA models based on contrast-enhanced CT images had a high value in differentiating fpAML from chRCC.

9.
Chem Commun (Camb) ; 55(86): 13004-13007, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31608907

RESUMO

An ultrasonication-promoted strategy was proposed to synthesize luminescent S-dots, which reduced the synthesis time from the commonly used 5 days to several hours. The as-synthesized S-dots show a high photostability and low cytotoxicity, and are then successfully applied for cellular imaging.


Assuntos
Pontos Quânticos/química , Enxofre/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Microscopia Confocal , Polietilenoglicóis/química , Pontos Quânticos/toxicidade , Sonicação
10.
Fish Shellfish Immunol ; 94: 346-354, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499205

RESUMO

Nk-lysin is an effector protein of cytotoxic T lymphocytes and natural killer cells. It is known to possess anti-bacterial, anti-fungal, anti-viral, and anti-tumor activity. Here we describe five Nk-lysin genes (PbNkla, PbNklb, PbNklc, PbNkld, and PbNkle) from Pseudocrossocheilus bamaensis, a rare indigenous species distributed in Guangxi, China. The open reading frames (ORFs) consisted of 426 (PbNkla), 435 (PbNklb), 369 (PbNklc), 366 (PbNkld), and 339 (PbNkle) bp nucleic acids. The surfactant-associated protein B (SapB) domain and six conserved cysteine residues were identified in each PbNkl gene. Phylogenetic analysis revealed similar results to homology comparison that PbNkla and PbNklb consist of five exons and four introns and grouped together, whereas PbNklc and PbNkld each contain four exons and three introns and formed a separate clade. PbNkle had three exons and two introns and formed an independent clade separate from the four other PbNkls. qPCR analysis demonstrated that PbNkla, PbNklc, PbNkld, and PbNkle were ubiquitously expressed in all tissues examined, whereas PbNklb was expressed only after bacterial infection. Aeromonas hydrophila challenge significantly up- and down-regulated PbNkls at different time points post-injection and in different immune-related tissues. These results suggested that PbNkls were conserved immune molecules that may be involved in the immune response to pathogen invasion.


Assuntos
Cyprinidae/genética , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Proteolipídeos/genética , Proteolipídeos/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Filogenia , Proteolipídeos/química , Alinhamento de Sequência/veterinária
11.
Genes (Basel) ; 10(7)2019 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-31284601

RESUMO

Previous study has demonstrated that the riboflavin treatment promoted the early ripening of the 'Kyoho' grape berry. However, the molecular mechanism causing this was unclear. In order to reveal the regulation mechanism of riboflavin treatment on grape berry development and ripening, the different berry developmental stages of the 'Kyoho' berry treated with 0.5 mmol/L of riboflavin was sampled for transcriptome profiling. RNA-seq revealed that 1526 and 430 genes were up-regulated and down-regulated, respectively, for the comparisons of the treatment to the control. TCseq analysis showed that the expression patterns of most of the genes were similar between the treatment and the control, except for some genes that were related to the chlorophyll metabolism, photosynthesis-antenna proteins, and photosynthesis, which were revealed by the enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The differentially expressed genes and weighted gene co-expression network analysis (WGCNA) analysis identified some significantly differentially expressed genes and some hub genes, including up-regulation of the photosynthesis-related ELIP1 and growth and development-related GDSL; and down-regulation of the oxidative stress-related ATHSP22 and berry softening-related XTH32 and GH9B15. The results suggested that the riboflavin treatment resulted in the variations of the expression levels of these genes, and then led to the early ripening of the 'Kyoho' berry.


Assuntos
Frutas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Riboflavina/farmacologia , Vitis/efeitos dos fármacos , Frutas/genética , Vitis/genética
12.
Sci Rep ; 9(1): 9820, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285444

RESUMO

MicroRNA-212-3p inhibits several human cancers but its effects on hepatocellular carcinoma (HCC) remain unclear. In this study, we show that miR-212-3p is down-regulated in HCC cell lines and tissues, and correlates with vascular invasion (p = 0.001), and the absence of capsule formation (p = 0.009). We found that miR-212-3p influenced the epithelial to mesenchymal transition (EMT) of HCCLM3 and Huh7 cells. Mechanistically, miR-212-3p repressed cell invasion through the suppression of connective tissue growth factor (CTGF). We therefore validate the anti-HCC effects of miR-212-3p through its ability to suppress CTGF and subsequent EMT.

13.
Mol Carcinog ; 58(10): 1897-1907, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31313392

RESUMO

The mechanism of hepatocellular carcinoma (HCC) metastasis remains poorly understood. Tropomodulin 3 (TMOD3) is a member of the pointed end capping protein family that contributes to invasion and metastasis in several types of malignancies. It has been found to be crucial for the membranous skeleton and embryonic development, although, its role in HCC progression remains largely unclear. We observed increased levels of Tmod3 in HCCs, especially in extrahepatic metastasis. High Tmod3 expression correlated with aggressive carcinoma and poor patient with HCC survival. Loss-of-function studies conducted by us determined Tmod3 as an oncogene that promoted HCC growth and metastasis. Mechanistically, Tmod3 increases transcription of matrix metalloproteinase-2, -7, and -9 which required PI3K-AKT. Interaction between Tmod3 and epidermal growth factor receptor (EGFR) that supports the activation of EGFR phosphorylation, is essential for signaling activation of PI3K-AKT viral oncogene homolog. These findings reveal that Tmod3 enhances aggressive behavior of HCC both in vitro and in vivo by interacting with EFGR and by activating the PI3K-AKT signaling pathway.


Assuntos
Carcinoma Hepatocelular/genética , Proliferação de Células/genética , Neoplasias Hepáticas/genética , Tropomodulina/genética , Animais , Carcinoma Hepatocelular/patologia , Progressão da Doença , Intervalo Livre de Doença , Transição Epitelial-Mesenquimal/genética , Receptores ErbB/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Proteína Oncogênica v-akt/genética , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais/genética
14.
J Hematol Oncol ; 12(1): 57, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182121

RESUMO

BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy simultaneously against CD19 and CD22 is an attractive strategy to address the antigen escape relapse after CD19-directed CAR-T cell therapies. However, the potential of optimizing the durability of remission by this approach in patients with B cell acute lymphoblastic leukemia (B-ALL) remains a critical unanswered question so far. CASE PRESENTATION: We treated an adult patient with relapsed and refractory B-ALL after haploidentical hematopoietic stem cell transplantation (HSCT) by administering haploidentical CAR-T cells targeting both CD19 and CD22 following preparative lymphodepleting chemotherapy. This patient has remained in minimal residual disease-negative remission for more than 14 months and has been tapered off graft versus host disease prophylaxis. CONCLUSIONS: CAR simultaneously targeting CD19 and CD22 has the potential of inducing long-term remission in patients with B-ALL.

15.
Analyst ; 144(14): 4425-4431, 2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31215573

RESUMO

Electrochemiluminescence (ECL) sensors are useful for the detection of heavy metal pollutants, in particular mercury(ii) ions, in water samples. We demonstrate the superior sensing performance of Hg2+ using a nanocomposite material based on carbon nitride nanosheets (CNNSs) and copper nanoclusters functionalized by dithiothreitol, which not only stabilizes the clusters, but also improves the sensitivity of Hg2+ detection. The ECL mechanism is related to the reaction of the nanocomposite with K2S2O8 in the electrochemical system, while the presence of Hg2+ leads to quenching of its excited state, and the suppression of the formation of anion-radicals. The Hg(ii) sensor presented here is cheap and fast, and shows high selectivity for the detection of Hg2+ on the background of other mono-, di-, and trivalent ions, with a linear range of 0.5-10 nM and the detection limit as low as 0.01 nM.

16.
Angew Chem Int Ed Engl ; 58(21): 7040-7044, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-30924228

RESUMO

An H2 O2 -assisted top-down approach is used to synthesize brightly luminescent, color-tunable sulfur quantum dots (SQDs), with a photoluminescence quantum yield of up to 23 %. The formation of SQDs involves dissolution of bulk sulfur powder into small particles in an alkaline environment in the presence of polyethylene glycol, followed by H2 O2 -assisted etching of polysulfide species, which has the advantage of the passivation of surface states. This synthetic strategy allows us to simultaneously control the final size of SQDs, to tune their emission color, and to improve their emission quantum yield by eliminating surface traps. Down-conversion white light emitting diodes were also fabricated using blue emissive SQDs and orange emissive copper nanoclusters, with CIE color coordinates of (0.33, 0.32) and a high color rendering index of 91. The water-soluble, highly luminescent SQDs are promising luminescent materials that can be produced from abundant precursor materials.

17.
Zhongguo Fei Ai Za Zhi ; 22(3): 167-172, 2019 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-30909997

RESUMO

Tumor-node-metastasis (TNM) staging system is the most important basis for making therapeutic decisions and predicting prognosis of lung cancer patients. The metabolic parameters including standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured by ¹8F-fluorodeoxyglucose-positron emission tomography (¹8F-FDG PET/CT) associate with tumor aggressiveness and can provide additional prognostic information. A new staging methodology combines the conventional cTNM with the metabolic tumor burden quantified from the PET images is a better predictor of overall survival with superior stratifying power may help oncologists to make better treatment plans. ¹8F-FDG PET/CT image texture analysis, as an emerging research tool, is used to quantify the spatial heterogeneity of radioactive uptake in tumors, thereby to explore the biological characteristics of the tumor. This article reviews developments in evaluating the ¹8F-FDG PET/CT metabolic parameters and its role as a prognostic factor for non-small cell lung cancer.
.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Humanos , Processamento de Imagem Assistida por Computador , Prognóstico
18.
Clin Nucl Med ; 44(4): 299-300, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30688747

RESUMO

Kimura's disease is a clinically rare, chronic, benign lymphoproliferative disorder of unknown etiology. A 36-year-old man presented with painless axillary swelling, which was suspected as lymphoma. PET/CT was performed for staging. The images showed multiple foci of increased activity in bilateral axillary and right inguinal lymph nodes. Laboratory tests revealed an increased eosinophil ratio and eosinophil count. Pathological examination from dissected axillary lymph nodes was consistent with Kimura's disease.


Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/complicações , Fluordesoxiglucose F18 , Linfadenopatia/diagnóstico por imagem , Linfadenopatia/etiologia , Linfoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Diagnóstico Diferencial , Humanos , Masculino
19.
J Hepatol ; 70(5): 904-917, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30654066

RESUMO

BACKGROUND & AIMS: Genetic variability in the hepatitis B virus X gene (HBx) is frequently observed and is associated with hepatocellular carcinoma (HCC) progression. However, a genotype classification based on the full-length HBx sequence and the impact of genotypes on hepatitis B virus (HBV)-related HCC prognosis remain unclear. We therefore aimed to perform this genotype classification and assess its clinical impact. METHODS: We classified the genotypes of the full-length HBx gene through sequencing and a cluster analysis of HBx DNA from a cohort of patients with HBV-related HCC, which served as the primary cohort (n = 284). Two independent HBV-related HCC cohorts, a validation cohort (n = 171) and a serum cohort (n = 168), were used to verify the results. Protein microarray assay analysis was performed to explore the underlying mechanism. RESULTS: In the primary cohort, the HBx DNA was classified into 3 genotypes: HBx-EHBH1, HBx-EHBH2, and HBx-EHBH3. HBx-EHBH2 (HBx-E2) indicated better recurrence-free survival and overall survival for patients with HCC. HBx-E2 was significantly correlated with the absence of liver cirrhosis, a small tumor size, a solitary tumor, complete encapsulation and Barcelona Clinic Liver Cancer (BCLC) stage A-0 tumors. Additionally, HBx-E2 served as a significant prognostic factor for patients with BCLC stage B HCC after hepatectomy. Mechanistically, HBx-E2 is unable to promote proliferation in HCC cells and normal hepatocytes. It also fails to activate the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3)/STAT5 pathway. CONCLUSION: Our study identifies a novel HBx genotype that is unable to promote the proliferation of HCC cells and suggests a potential marker to preoperatively predict the prognosis of patients with BCLC stage B, HBV-associated, HCC. LAY SUMMARY: We classified a novel genotype of the full-length hepatitis B virus X gene (HBx), HBx-E2. This genotype was identified in tumor and nontumor tissues from patients with hepatitis B virus-related hepatocellular carcinoma. HBx-E2 could preoperatively predict the prognosis of patients with intermediate stage hepatocellular carcinoma, after resection.

20.
Oncol Lett ; 17(2): 2317-2327, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30675297

RESUMO

MicroRNAs (miRNAs) serve an important regulatory role in carcinogenesis and cancer progression. Aberrant expression of miR-197-3p has been reported in various human malignancies. However, the role of miR-197-3p in the progression and prognosis of hepatocellular carcinoma (HCC) remains unknown. The present study demonstrated that miR-197-3p was downregulated in HCC tissues and that the low level of miR-197-3p expression in HCC tumours correlated with aggressive clinicopathological characteristics; thus, miR-197-3p may serve as a predictor for poor prognosis in patients with HCC. Additionally, miR-197-3p markedly inhibited the metastasis of HCC cells in vitro and in vivo. Bioinformatics analysis further identified zinc finger protein interacted with K protein 1 (ZIK1) as a novel target of miR-197-3p in HCC cells. These findings suggest that miR-197-3p may regulate the survival of HCC cells, partially through the downregulation of ZIK1. Therefore, the miR-197-3p/ZIK1 axis may serve as a novel therapeutic target in patients with HCC.

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