RESUMEN
Endoscopic optical coherence tomography (OCT) possesses the capability to non-invasively image internal lumens; however, it is susceptible to saturation artifacts arising from robust reflective structures. In this study, we introduce an innovative deep learning network, ATN-Res2Unet, designed to mitigate saturation artifacts in endoscopic OCT images. This is achieved through the integration of multi-scale perception, multi-attention mechanisms, and frequency domain filters. To address the challenge of obtaining ground truth in endoscopic OCT, we propose a method for constructing training data pairs. Experimental in vivo data substantiates the effectiveness of ATN-Res2Unet in reducing diverse artifacts while preserving structural information. Comparative analysis with prior studies reveals a notable enhancement, with average quantitative indicators increasing by 45.4-83.8%. Significantly, this study marks the inaugural exploration of leveraging deep learning to eradicate artifacts from endoscopic OCT images, presenting considerable potential for clinical applications.
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Artefactos , Aprendizaje Profundo , Endoscopía , Tomografía de Coherencia Óptica , Tomografía de Coherencia Óptica/métodos , Endoscopía/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
PURPOSE: The immediate plasma metabolism and development of chemo-resistance (single agent) severely hampers the clinical effectiveness of Sorafenib (SRF) in liver cancer therapy. MicroRNA27a inhibition is a promising biological strategy for breast cancer therapy. METHODS: In this study, we aimed to prepare SRF and anti-miRNA27a-loaded anti-GPC3 antibody targeted lipid nanoparticles to enhance the therapeutic efficacy against liver cancers. In this study, we have employed a unique cationic switchable lipid (CSL) as a mean to encapsulate miRNA as well as to confer pH-responsiveness to the nanocarrier system. RESULTS: The G-S27LN was nanosized and offered a pH-responsive release of SRF from the carrier system and we have demonstrated the specific affinity of G-S27LN towards the GPC3-overexpressed HepG2 cancer cells. Anti-microRNA27a significantly increased the protein expression of FOXO1 and PPAR-γ which are crucial components involved in proliferation and apoptosis of tumor cells. Combination of SRF and anti-miRNA27a (G-S27LN) resulted in significantly lower cell viability with a marked increase in the apoptosis cell proportion compared to that of free SRF indicating the synergistic anticancer effect. Animal studies in liver cancer xenograft model demonstrated significant suppression of tumor burden, reduced tumor cell and elevated TUNEL positive apoptosis with no toxicity concerns in animals treated with G-S27LN formulation. CONCLUSION: The CSL-based G-S27LN efficiently co-delivered anti-microRNA27a and SRF and therefore represents a promising therapy to treat liver cancer. This study also brings forth a platform strategy for the effective treatment of number of other advanced cancers.
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Antagomirs/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Glipicanos/inmunología , Lípidos/química , Neoplasias Hepáticas/tratamiento farmacológico , MicroARNs/inmunología , Nanopartículas/química , Sorafenib/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colesterol/química , Sinergismo Farmacológico , Proteína Forkhead Box O1/metabolismo , Células Hep G2 , Humanos , Concentración de Iones de Hidrógeno , Ratones Endogámicos BALB C , Ratones Desnudos , PPAR gamma/metabolismo , Fosforilcolina/química , Polietilenglicoles/químicaRESUMEN
BACKGROUND/AIMS: Ischemic postconditioning (iPoC) represents a promising strategy to mitigate ischemia/reperfusion (I/R) injury of the intestine, yet the mechanisms of this treatment remain to be elucidated. Circular RNAs (circRNAs), a novel class of endogenous non-coding RNAs, have recently been recognized as important regulators of gene expression and pathological processes. Here, we aimed to investigate the expression patterns of circRNAs after intestinal I/R with and without iPoC and, furthermore, to explore the potential mechanisms of iPoC in relation to the differentially expressed circRNAs. METHODS: The global circRNA and mRNA expression profiles in mouse intestinal mucosa were initially screened by microarray (n = 3 per group) and quantitative real-time PCR was used to validate the expression pattern of circRNAs and mRNAs. Bioinformatics analysis including Gene ontology, KEGG pathway analysis, microRNA binding sites identification and circRNA-miRNA-mRNA network construction were utilized for in-depth mechanism exploration. RESULTS: There were 4 up- and 58 downregulated circRNAs as well as 322 up- and 199 downregulated mRNAs in the intestinal I/R group compared with the sham group, whereas compared with I/R, iPoC treatment significantly upregulated 12 circRNAs and 129 mRNAs and downregulated 21 circRNAs and 174 mRNAs. The expression levels of a randomly selected set of 6 circRNAs and 5 mRNAs were successfully validated by qRT-PCR. Through a systematic comparison of the direction of circRNA expression changes in all groups, we identified two circRNAs, circRNA_012412 and circRNA_016863, that may be closely associated with the protective mechanisms of iPoC. Finally, four possible circRNA_012412/circRNA_016863-miRNA-mRNA pathways were predicted, which may play important roles in endogenous protective signaling in iPoC. CONCLUSIONS: This study was the first to comprehensively delineate the expression profiles of circRNAs in a mouse model of intestinal I/R and iPoC and provides novel clues for understanding the mechanisms of iPoC against intestinal I/R injury.
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Intestinos/patología , ARN/metabolismo , Daño por Reperfusión/patología , Animales , Biología Computacional , Modelos Animales de Enfermedad , Regulación hacia Abajo , Poscondicionamiento Isquémico , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Circular , ARN Mensajero/metabolismo , Daño por Reperfusión/genética , Factor de Necrosis Tumoral alfa/sangre , Regulación hacia ArribaRESUMEN
BACKGROUND/AIMS: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. METHODS: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. RESULTS: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. CONCLUSION: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.
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Proliferación Celular , Transición Epitelial-Mesenquimal , Janus Quinasa 2/metabolismo , ARN Largo no Codificante/metabolismo , Factor de Transcripción STAT3/metabolismo , Adulto , Anciano , Cadherinas/genética , Cadherinas/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular , Femenino , Humanos , Janus Quinasa 2/genética , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Interferencia de ARN , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo , Factor de Transcripción STAT3/genética , Transducción de Señal , Vimentina/genética , Vimentina/metabolismoRESUMEN
Mycotoxins produced by different species of fungi may coexist in cereals and feedstuffs, and could be highly toxic for humans and animals. For quantification of multiple mycotoxins in cereals, we developed a paper-based mycotoxin immune-affinity array. First, paper-based microzone arrays were fabricated by photolithography. Then, monoclonal mycotoxin antibodies were added in a copolymerization reaction with a cross-linker to form an immune-affinity monolith on the paper-based microzone array. With use of a competitive immune-response format, paper-based mycotoxin immune-affinity arrays were successfully applied to detect mycotoxins in samples. The detection limits for deoxynivalenol, zearalenone, T-2 toxin, and HT-2 toxin were 62.7, 10.8, 0.36, and 0.23 µg·kg-1, respectively, which meet relevant requirements for these compounds in food. The recovery rates were 81-86% for deoxynivalenol, 89-117% for zearalenone, 79-86% for T-2 toxin, and 78-83% for HT-2 toxin, and showed the paper-based immune-affinity arrays had good reproducibility. In summary, the paper-based mycotoxin immune-affinity array provides a sensitive, rapid, accurate, stable, and convenient platform for detection of multiple mycotoxins in agro-foods. Graphical abstract Paper-based immune-affinity monolithic array. DON deoxynivalenol, HT-2 HT-2 toxin, T-2 T-2 toxin, PEGDA polyethylene glycol diacrylate, ZEN zearalenone.
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Anticuerpos Inmovilizados/química , Grano Comestible/química , Análisis de los Alimentos/métodos , Contaminación de Alimentos/análisis , Inmunoensayo/métodos , Micotoxinas/análisis , Papel , Animales , Diseño de Equipo , Análisis de los Alimentos/instrumentación , Humanos , Inmunoensayo/instrumentación , Límite de Detección , Mediciones Luminiscentes/instrumentación , Mediciones Luminiscentes/métodos , Polimerizacion , Reproducibilidad de los Resultados , Toxina T-2/análogos & derivados , Toxina T-2/análisis , Tricotecenos/análisis , Zearalenona/análisisRESUMEN
Aberrant sialylation profiles on the cell surface have been recognized for their potential diagnostic value in identifying the regulation of tumor properties in several cancers, including hepatocellular carcinoma (HCC). Recently, increasing evidence has suggested that the deregulation of microRNA (miRNA) is a common feature in human cancers. In this study, we found obvious upregulation of sialyltransferase ST3GAL6 both in HCC cell lines and in tissue samples. The altered expression of ST3GAL6 was found to correlate with cell proliferation, migration, and invasion ability in HCC. Further investigation showed that miR-26a negatively regulated ST3GAL6, inducing the suppression of cell proliferation, migration, and invasion in vitro. Moreover, we identified the protein kinase B/mammalian target of rapamycin (Akt/mTOR) pathway as the target of ST3GAL6 based on Western blot analysis. Analysis of a xenograft mouse model showed that miR-26a significantly reduced tumor growth by suppressing activation of the Akt/mTOR pathway by directly targeting ST3GAL6. In conclusion, these data indicate that ST3GAL6 promotes cell growth, migration, and invasion and mediates the effect of miR-26a through the Akt/mTOR signaling pathway in HCC.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , MicroARNs/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sialiltransferasas/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundario , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Humanos , Neoplasias Hepáticas/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Transducción de Señal , Ensayo de Tumor de Célula Madre , Regulación hacia Arriba , beta-Galactosida alfa-2,3-SialiltransferasaRESUMEN
BACKGROUND: Mycotoxins are produced by fungi as secondary metabolites. They often multi-contaminate food and feed commodities posing a health risk to humans and animals. Fast and easy multiplex screening could be thought as a useful tool for detection of multi-contaminated food and feed commodities. RESULTS: A highly sensitive immune-affinity monolithic arrays for detecting the mycotoxins zearalenone, deoxynivalenol, T-2 toxin, HT-2 toxin, aflatoxins, ochratoxin A, and fumonisin B1 were fabricated using UV induced co-polymerisation. The mycotoxin antibodies firstly reacted with functional monomer to form antibody/functional monomer bio-conjugates. Subsequently, the antibody/functional monomer bio-conjugates co-polymerised with cross-linker to form mycotoxins immune-affinity arrays. With optimal fabrication conditions, all mycotoxin immune-affinity monolithic arrays exhibited a linear response spanning three orders of magnitude. And the immune-affinity monolithic array has a low detection limit and has a good uniformity (intra-assay CV, and inter-assay CV both <8%). CONCLUSION: The fabricated mycotoxin immune-affinity monolithic arrays were proved as a sensitive, stable and economical tool in real food samples detection. Moreover, the mycotoxin immune-affinity monolithic arrays would be able to minimise manipulation steps: add samples and enzyme labelled mycotoxins, and detect CL signals. © 2016 Society of Chemical Industry.
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Contaminación de Alimentos/análisis , Hordeum/química , Mediciones Luminiscentes/métodos , Micotoxinas/análisis , Análisis por Matrices de Proteínas/métodos , Anticuerpos Inmovilizados/química , Microbiología de Alimentos , Hordeum/microbiología , Inmunoensayo/métodosRESUMEN
To investigate whether the mitochondrial apoptotic pathway mediates myocardial cell injuries in rats under brain death (BD), and observe the effects and mechanisms of the c-Jun N-terminal kinase (JNK) inhibitor SP600125 on cell death in the heart. Forty healthy male Sprague-Dawley (SD) rats were randomized into four groups: sham group (dural external catheter with no BD); BD group (maintain the induced BD state for 6 hrs); BD + SP600125 group (intraperitoneal injection of SP600125 10 mg/kg 1 hr before inducing BD, and maintain BD for 6 hrs); and BD + Dimethyl Sulphoxide (DMSO) group (intraperitoneal injection of DMSO 1 hr before inducing BD, and maintain BD for 6 hrs). Real-time quantitative PCR was used to evaluate mRNA levels of Cyt-c and caspase-3. Western blot analysis was performed to examine the levels of mitochondrial apoptosis-related proteins p-JNK, Bcl-2, Bax, Cyt-c and Caspase-3. TUNEL assay was employed to evaluate myocardial apoptosis. Compared with the sham group, the BD group exhibited increased mitochondrial apoptosis-related gene expression, accompanied by the elevation of p-JNK expression and myocardial apoptosis. As the vehicle control, DMSO had no treatment effects. The BD + SP600125 group had decreased p-JNK expression, and reduced mitochondrial apoptosis-related gene expression. Furthermore, the apoptosis rate of myocardial cells was reduced. The JNK inhibitor SP600125 could protect myocardial cells under BD through the inhibition of mitochondrial apoptosis-related pathways.
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Antracenos/farmacología , Muerte Encefálica/patología , Cardiotónicos/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Miocardio/patología , Inhibidores de Proteínas Quinasas/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Caspasa 3/metabolismo , Citocromos c/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Mitocondrias/genética , Miocardio/metabolismo , Fosforilación/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Altered sialylation is closely associated with tumor progression and invasiveness. Micro-RNAs endogenous regulators of gene expression have been implicated in human thyroid carcinoma invasiveness. The objective of this study is to examine the alterations of miR-4299 and ST6GALNAC family in human follicular thyroid carcinoma during metastatic process. qRT-PCR showed the differential expressional profiles of miR-4299 and ST6GALNAC family in three kinds of thyroid cell lines (FTC-133,FTC-238, Nthy-ori 3-1) and clinical tissue specimens(malignant and borderline). The altered expression levels of ST6GALNAC4 were corresponding to invasive phenotypes of FTC-133 and FTC-238 cells both in vitro and in vivo. Further date indicated that miR-4299 regulated tumor progression and invasiveness by directly targeting ST6GALNAC4. This study implies the potential therapeutic application of miR-4299 and ST6GALNAC4 in modulating the invasion and tumorigenicity of follicular thyroid carcinoma cell.
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Adenocarcinoma Folicular/genética , Carcinogénesis/genética , MicroARNs/biosíntesis , Sialiltransferasas/biosíntesis , Adenocarcinoma Folicular/patología , Animales , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , MicroARNs/genética , Invasividad Neoplásica/genética , Metástasis de la Neoplasia , Sialiltransferasas/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Carbohydrate sulfotransferases 11-13 (CHST11-13), that catalyze the transfer of sulfate to position 4 of the GalNAc residue of chondroitin, have been implicated in various diseases. AIM: This study aimed to clarify the association of CHST11-13 expression with metastasis and drug sensitivity in hepatocellular carcinoma (HCC) cells. METHODS: We measured the levels of CHST11 and CHST13 in a series of HCC cells using real-time PCR and Western blotting. After RNAi and forced expression treatment of CHST11 and CHST13 in MHCC97L and MHCC97H cells, metastatic potential and drug sensitivity of the two cells were investigated with ECM invasion assay, drug sensitivity assay, and in vivo antitumor activity assay. By real-time PCR and Western blotting, we explored the possible impacts of these two genes on mitogen-activated protein kinase (MAPK) signal pathway. MAPK pathway was blocked by PD98059 or SP600125 to elucidate the effects of MAPK pathway on metastasis and chemosensitivity. RESULTS: Significantly reduced levels of CHST11 and CHST13 were observed in highly invasive MHCC97H cells compared with those of MHCC97L cell line with low metastatic potential. Decreased or forced expression of CHST11 and CHST13 altered metastatic potential and drug sensitivity of MHCC97L and MHCC97H cells. Remarkable alteration of MAPK activity was shown in two HCC cells with genetic manipulation. Conversely, pharmacologic inhibition of the MAPK pathway suppressed invasive potential and rescued drug sensitivity of MHCC97H cells. CONCLUSIONS: Our results have demonstrated that CHST11 and CHST13 negatively modulate metastasis and drug resistance of HCC cells probably via oncogenic MAPK signal pathway.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Metástasis de la Neoplasia/fisiopatología , Sulfotransferasas/metabolismo , Línea Celular Tumoral , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/fisiología , Técnicas de Silenciamiento del Gen , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Persona de Mediana Edad , ARN Interferente Pequeño/metabolismo , Sulfotransferasas/genéticaRESUMEN
Aberrant sialylation is closely associated with malignant phenotypes of tumor cells, including invasiveness and metastasis. This study investigated sialylation with regard to the modification of invasive properties and chemosensitivity in human hepatocellular carcinoma (HCC) cell lines and the association between the sialyltransferase gene family and clinicopathological characteristics in HCC patients. Using mass spectrometry analysis, we found that the composition profiling of sialylated N-glycans differed between MHCC97H and MHCC97L cells with different metastatic potential. The expressional profiles of 20 sialyltransferase genes showed differential expression in two cell lines, transitional and tumor tissues, from the same patients. Two genes, ST6GAL1 and ST8SIA2, were detected as overexpressed in MHCC97H and MHCC97L cells. The altered expression levels of ST6GAL1 and ST8SIA2 corresponded to a changed invasive phenotype and chemosensitivity of MHCC97H and MHCC97L cells both in vitro and in vivo. Further data indicated that manipulation of the expression of the two genes led to altered activity of the phosphoinositide-3 kinase (PI3K)/Akt signaling pathway. Targeting the PI3K/Akt pathway by its specific inhibitor wortmannin or by Akt RNA interference resulted in a reduced capacity for invasion and chemoresistance of MHCC97H cells. Our results imply that sialylation may function as an internal factor, regulating the invasion and chemosensitivity of HCC, probably through ST6GAL1 or ST8SIA2 regulation of the activity of the PI3K/Akt pathway.
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Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Resistencia a Antineoplásicos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Ácido N-Acetilneuramínico/metabolismo , Sialiltransferasas/metabolismo , Adulto , Anciano , Metabolismo de los Hidratos de Carbono/genética , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Resistencia a Antineoplásicos/genética , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Procesamiento Proteico-Postraduccional/genética , Sialiltransferasas/genética , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to evaluate the clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC). METHODS: Data from 117 patients with HCC who underwent hepatectomy between December 2010 and February 2014 were retrospectively reviewed. In total, 55 patients underwent surgical resection only (group A), and 62 patients underwent surgical resection with adjuvant TACE (group B). The perioperative clinical indicators, postoperative sequential treatment, and follow-up were compared between the two groups of patients. The Kaplan-Meier method was used to compare survival between the groups, and prognostic factors were evaluated by a Cox proportional hazard model. RESULTS: The two groups showed no significant difference in age, gender, preoperative A-fetoprotein (AFP) values, preoperative Child-Pugh score, hepatitis B virus(HBV) DNA levels, duration of surgery, hepatectomy technique, albumin values 1-week postoperative, postoperative complications, duration of postoperative hospital stay, cirrhosis, tumor size, tumor differentiation, tumor encapsulation, satellite nodules, or microvascular infiltration. Cox regression analysis revealed that tumor size, satellite nodules, and microvascular infiltration were significantly independent prognostic factors (P = 0.001, 0.002, and 0.001). Of the 117 patients, the 1-, 2-, and 3-year disease-free survival rates were 64.5, 50.0, and 41.9%, respectively, for group B (62 patients) and 45.5, 36.4, and 30.9%, respectively, for group A (55 patients). Although improving trends of disease-free survival were observed in the adjuvant TACE group, there was a significant difference in postoperative 1-year survival between the two groups (P = 0.04) but no significant difference in postoperative 2- and 3-year survival. In patients with tumor size >5 cm, the 1-, 2-, and 3-year disease-free survival rates were 41.7, 25.0, and 12.5%, respectively, for group B and 11.8, 0, and 0%, respectively, for group A. There was a significant difference in postoperative 1- and 2-year survival between the two groups (P = 0.04 and 0.03, respectively) but no significant difference in postoperative 3-year survival. In patients with microvascular infiltration, the 1-, 2-, and 3-year disease-free survival rates were 42.3, 26.9, and 15.4%, respectively, for group B and 12.5, 4.2, and 0%, respectively, for group A. There was a significant difference between the two groups (P = 0.02, 0.03, and 0.045, respectively). In patients with satellite nodules, the 1-, 2-, and 3-year disease-free survival rates were 50.0, 50, and 40%, respectively, for group B and 17.6, 0, and 0%, respectively, for group A. There was a significant difference between the two groups (P = 0.04, 0.01, and 0.03, respectively). In patients with tumor size ≤5 cm, without satellite nodules, or without microvascular infiltration, there was no significant difference between the two groups in the 1-, 2-, or 3-year disease-free survival rates. Of 117 patients overall, 18 (15.4%) developed hepatitis B virus reactivation: 2 (3.6%) patients in group A and 16 (25.8%) patients in group B. There was a significant difference between the two groups (P = 0.000). Of these patients, one (1.8 %) patient in group A and five (8.1 %) patients in group B developed hepatitis due to hepatitis B virus reactivation. There was a significant difference between the two groups (P = 0.000). CONCLUSIONS: Postoperative adjuvant TACE can improve the 1-year disease-free survival rate of HCC patients. Postoperative adjuvant TACE may improve 2- and 3-year disease-free survival rates, but no statistical significance was found. For patients with tumor size >5 cm, postoperative adjuvant TACE can improve 1- and 2-year disease-free survival rates, and postoperative adjuvant TACE may improve the 3-year disease-free survival rate. For HCC patients with tumor size ≤5 cm, postoperative adjuvant TACE may improve the 1-, 2-, and 3-year disease-free survival rates, but no statistical significance was found. For patients with microvascular infiltration or satellite nodules, postoperative adjuvant TACE can improve the 1-, 2-, and 3-year disease-free survival rates. For patients without microvascular infiltration or without satellite nodules, postoperative adjuvant TACE cannot improve 1-, 2-, or 3-year disease-free survival rates. For patients with tumor size >5 cm with microvascular infiltration or with satellite nodules, postoperative adjuvant TACE was suggested. Hepatitis B virus reactivation can occur in patients with postoperative adjuvant TACE; thus, antiviral treatment was suggested for these patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica , Hepatectomía , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/terapia , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Periodo Posoperatorio , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The invasion and chemoresistance are crucial causes of morbidity and death for cancer patients. Axl is closely associated with malignant phenotype of breast tumor cells, including invasiveness and metastasis. Both breast cancer cell line and tissue displayed increased expression of Axl, especially in highly metastatic breast cancer. On the contrary, experimental inhibition of Axl or transforming growth factor beta 1 (TGF-ß1) by RNAi assay could suppress cell invasion ability and chemoresistance. Moreover, the up-regulation of Axl was induced by TGF-ß1, further activated phosphatidylinositol 3-kinase (PI3K)/Akt and PAK1 translocation, and resulted in greater cell motility, invasion, and chemoresistance in vitro and in vivo. After the detection and statistics in human breast cancer specimens, we found that the Axl expression was closely correlated with TGF-ß1 level, tumor differentiation, lymph node metastasis, and clinical stage (p < 0.01). Our findings support the possibility that Axl is a significant regulator of invasion and chemosensitivity, and it means by targeting Axl or its related signaling pathways, we can reduce the invasion and chemosensitivity of breast tumor.
Asunto(s)
Neoplasias de la Mama/genética , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Tirosina Quinasas Receptoras/biosíntesis , Factor de Crecimiento Transformador beta/biosíntesis , Quinasas p21 Activadas/biosíntesis , Animales , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Células MCF-7 , Ratones , Invasividad Neoplásica/genética , Fosfatidilinositol 3-Quinasas/biosíntesis , Fosfatidilinositol 3-Quinasas/genética , Transducción de Señal , Factor de Crecimiento Transformador beta/genética , Tirosina Quinasa del Receptor AxlRESUMEN
PURPOSE: Increasing investigations have been performed on the association of -607C/A polymorphism in Interleukin-18 (IL-18) gene promoter with cancer risk and have yielded conflicting results. To derive a more precise estimation of the association, we performed an updated meta-analysis of all eligible studies. METHODS: We searched all eligible studies by using PubMed, MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases. The odds ratios (ORs) were pooled by the fixed-effects/random-effects model in STATA 12.0 software. RESULTS: This meta-analysis included 29 studies with 6,026 cases and 6,476 controls. Overall, significantly increased cancer risk was observed (A vs C: OR=1.10, 95% CI: 1.01,1.19, Pheterogeneity=0.001; AA vs CC: OR=1.17, 95% CI: 1.01,1.37, Pheterogeneity=0.007; CA vs CC: OR=1.15, 95% CI: 1.05,1.25, Pheterogeneity=0.152; AA/CA vs CC: OR=1.17, 95% CI: 1.06,1.31, Pheterogeneity=0.042). In subgroup analyses based on ethnicity, the results suggested a significantly increased risk of cancer in Asian population (CA vs CC: OR=1.11, 95% CI: 1.00-1.24, Pheterogeneity=0.353; AA/CA vs CC: OR=1.14, 95% CI: 1.02-1.29, Pheterogeneity=0.081) and in Mixed population (A vs C: OR=1.72, 95% CI: 1.22-2.43, Pheterogeneity=NA; AA vs CC: OR=2.84, 95% CI: 1.43-5.64, Pheterogeneity=NA; AA vs CC/CA: OR=2.43, 95% CI: 1.34-4.42, Pheterogeneity=NA; AA/CA vs CC: OR=1.69, 95% CI: 1.00-2.85, Pheterogeneity=NA); however, no significant association was found in Caucasian or African populations. In the subgroup analysis by cancer type we found a significantly increased susceptibility to breast cancer (A vs C: OR=1.33, 95% CI: 1.00-1.75,Pheterogeneity=0.155; AA vs CC: OR=1.80, 95% CI: 1.02-3.21,Pheterogeneity=0.162; AA7sol;CA vs CC: OR=1.33, 95% CI: 1.00-1.78,Pheterogeneity=0.546), nasopharyngeal carcinoma (A vs C: OR=1.16, 95% CI: 1.01-1.32, Pheterogeneity=0.921; AA vs CC: OR=1.34, 95% CI: 1.02-1.75, Pheterogeneity=0.863; CA vs. CC: OR=1.36, 95% CI: 1.08-1.70, Pheterogeneity=0.824; AA/CA vs CC: OR=1.35, 95% CI: 1.09-1.68,Pheterogeneity=0.904), and esophageal cancer (CA vs CC: OR=1.37, 95% CI: 1.04-1.80, Pheterogeneity=0.528; AA/CA vs CC: OR =1.29, 95% CI: 1.00-1.66, Pheterogeneity=0.700). CONCLUSIONS: The current meta-analysis suggests that the -607C/A polymorphism in IL-18 gene promoter is associated with a significantly increased risk of cancer, especially of breast cancer, nasopharyngeal carcinoma and esophageal cancer and in Asian and Mixed populations. More studies with diverse ethnic groups, larger sample size, and well controlled confounding factors are warranted to further investigate the association.
Asunto(s)
Interleucina-18/genética , Neoplasias/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Estudios de Casos y Controles , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Neoplasias/diagnóstico , Neoplasias/etnología , Neoplasias/inmunología , Oportunidad Relativa , Fenotipo , Medición de Riesgo , Factores de RiesgoRESUMEN
Metastasis of tumor cells is the most deadly attribute of breast cancer patients. Aberrant sialylation is closely associated with malignant phenotype of tumor cells, including invasiveness and metastasis. The objective of this study is to clarify the possible role and mechanism of ST6GalNAcII in the metastasis process of breast carcinoma. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAc II in breast carcinoma cell lines and tissue specimens. PI3K/AKt signaling pathway was also analyzed. The high expression level of ST6GalNAcII was corresponding to invasive phenotype of breast cancer cells both in vitro and in vivo. Further data indicated that manipulation of ST6GalNAcII gene expression led to alter the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway. Blocking the PI3K/Akt pathway resulted in reduced capacity in invasion of MDA-MB-231 cells. ST6GalNAcII elucidated the unusual properties of invasion in breast cancer cell via modulating the PI3K/AKt signaling pathway.
Asunto(s)
Neoplasias de la Mama/patología , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sialiltransferasas/metabolismo , Transducción de Señal , Animales , Western Blotting , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Proliferación Celular , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Femenino , Humanos , Técnicas para Inmunoenzimas , Ratones , Ratones Desnudos , FN-kappa B/genética , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Fosfatidilinositol 3-Quinasas/genética , Pronóstico , Proteínas Proto-Oncogénicas c-akt/genética , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sialiltransferasas/antagonistas & inhibidores , Sialiltransferasas/genética , Células Tumorales CultivadasRESUMEN
The invasion and chemoresistance are crucial causes of morbidity and relapse for cancer patients. Axl is implicated in the modulation of cell invasion, cancer metastasis, and chemosensitivity in human breast carcinoma cell lines. Both breast cancer cell lines and tissues displayed increased expression of Axl, and it over expressed in highly metastatic breast cancer. The altered expression level of Axl was corresponding to the changed invasive phenotype and chemosensitivity of MDA-MB-231 cells both in vitro and in vivo. Further data indicated that experimental inhibition of Axl by RNAi assay inhibited phosphatidylinositol 3-kinase (PI3K)/Akt/GSK3ß signaling pathway, resulted in the decrease of Slug expression, and further suppressed cell invasion properties and chemosensitivity. What is more, after the detection and statistics in human breast cancer specimens, we found the Axl expression was closely correlated with histological grade, lymph node metastasis, and clinical stage (P < 0.01). Taken together, these findings indicate that Axl exerts the role of tumor metastasis and chemosensitivity through activation of the PI3K/Akt/GSK3ß signaling pathway, which is transcriptionally regulated by Slug. Our findings support the possibility that Axl is a novel regulator. It means by targeting Axl or its related signaling pathways, we can reduce the invasion and chemosensitivity of breast tumor.
Asunto(s)
Neoplasias de la Mama/enzimología , Resistencia a Antineoplásicos , Proteínas Proto-Oncogénicas/fisiología , Proteínas Tirosina Quinasas Receptoras/fisiología , Factores de Transcripción/fisiología , Animales , Antimetabolitos Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Fluorouracilo/farmacología , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Factores de Transcripción de la Familia Snail , Transcripción Genética , Ensayos Antitumor por Modelo de Xenoinjerto , Tirosina Quinasa del Receptor AxlRESUMEN
The objective of this study is to clarify the possible role and mechanism of Axl in the tumorigenicity and metastasis process of hepatocellular carcinoma. The mRNA and protein expression levels of Axl in MHCC97-H and MHCC97-L cell lines were evaluated by real-time PCR and Western blot analysis. The key factor of phosphatidylinositol-3-kinase (PI3K)/Akt-p21-activated kinases-1 (PAK1) signaling pathway was studied after Axl expression was downregulated by shRNA. Finally, we analyzed the expression status of Axl protein expression in hepatocellular carcinoma tissues and its relationship with the prognosis of hepatocellular carcinoma. Axl was observed to be higher expressed in MHCC97-H cell lines compared to MHCC97-L cell lines. The downregulation of Axl in MHCC97-H cell lines resulted in the inhibition of the invasion ability of MHCC97-H cells both in vitro and in vivo. Interestingly, blocking PI3K/Akt signaling pathway by LY294002 or Akt siRNA could remarkably inhibit the PAK1 activation and cell invasion. Finally, the Axl protein expression was positively correlated with differentiation, lymph node metastasis, and clinical stage in patients with hepatocellular carcinoma patients (all P < 0.01). These findings suggest that Axl can also regulate the metastasis process of hepatocellular carcinoma and may serve as a new prognostic marker and therapeutic target for treating hepatocellular carcinoma metastasis.
Asunto(s)
Carcinoma Hepatocelular/secundario , Neoplasias Hepáticas/patología , Fosfatidilinositol 3-Quinasas/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Proteínas Proto-Oncogénicas/fisiología , Proteínas Tirosina Quinasas Receptoras/fisiología , Quinasas p21 Activadas/fisiología , Adulto , Anciano , Línea Celular Tumoral , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/análisis , Proteínas Tirosina Quinasas Receptoras/genética , Transducción de Señal , Tirosina Quinasa del Receptor AxlRESUMEN
Phyllodes tumor exhibits an aggressive growth. The expression of many biological markers has been explored to discriminate between different grades of phyllodes tumor and to predict their behavior. The purpose of this study was to evaluate the implications of Axl and ST6GalNAcII in phyllodes tumors. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAcII and Axl in phyllodes tumor (PT) cell lines and tissue specimens. RNAi assay, ECM invasion assay, and tumorigenicity assay were used to analyze the altered expression of ST6GalNAcII gene effects on the expression of Axl and invasive ability of phyllodes tumor cells in vitro and in vivo. Compared to benign tumors, borderline and malignant ones showed a remarkable increase in mRNA levels of Axl and ST6GalNAcII gene, and it was higher in malignant tumor cells than in borderline tumor cells. When ST6GalNAcII was silenced, compared to the control, the expression level of Axl was significantly reduced in malignant tumor cell transfectants and knockdown of ST6GalNAcII gene significantly inhibited invasive activity in malignant tumor cells. The high expression of ST6GalNAcII and Axl was significantly correlated with tumor grade and distance metastasis by immunohistochemical analysis. Axl and ST6GalNAcII expression increases with increasing tumor grade in mammary phyllodes tumors. ST6GalNAc II might be participated in the glycosylation of Axl, and this Axl glycosylation may mediate the tumorigenicity, invasion, and distant metastasis of PT cells.
Asunto(s)
Neoplasias de la Mama/metabolismo , Tumor Filoide/metabolismo , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Tirosina Quinasas Receptoras/biosíntesis , Sialiltransferasas/biosíntesis , Adulto , Anciano , Animales , Western Blotting , Neoplasias de la Mama/patología , Femenino , Xenoinjertos , Humanos , Inmunohistoquímica , Ratones , Persona de Mediana Edad , Invasividad Neoplásica , Tumor Filoide/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Matrices Tisulares , Transcriptoma , Tirosina Quinasa del Receptor AxlRESUMEN
Objective.The high-precision segmentation of retinal vessels in fundus images is important for the early diagnosis of ophthalmic diseases. However, the extraction for microvessels is challenging due to their characteristics of low contrast and high structural complexity. Although some works have been developed to improve the segmentation ability in thin vessels, they have only been successful in recognizing small vessels with relatively high contrast.Approach.Therefore, we develop a deep learning (DL) framework with a multi-stage and dual-channel network model (MSDC_NET) to further improve the thin-vessel segmentation with low contrast. Specifically, an adaptive image enhancement strategy combining multiple preprocessing and the DL method is firstly proposed to elevate the contrast of thin vessels; then, a two-channel model with multi-scale perception is developed to implement whole- and thin-vessel segmentation; and finally, a series of post-processing operations are designed to extract more small vessels in the predicted maps from thin-vessel channels.Main results.Experiments on DRIVE, STARE and CHASE_DB1 demonstrate the superiorities of the proposed MSDC_NET in extracting more thin vessels in fundus images, and quantitative evaluations on several parameters based on the advanced ground truth further verify the advantages of our proposed DL model. Compared with the previous multi-branch method, the specificity and F1score are improved by about 2.18%, 0.68%, 1.73% and 2.91%, 0.24%, 8.38% on the three datasets, respectively.Significance.This work may provide richer information to ophthalmologists for the diagnosis and treatment of vascular-related ophthalmic diseases.