RESUMEN
Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.
Asunto(s)
Aprendizaje Profundo , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Lesiones Precancerosas , Humanos , Persona de Mediana Edad , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Estudios Prospectivos , Lesiones Precancerosas/patologíaRESUMEN
Autophagy is a highly conserved metabolic process with a cytoprotective function. Autophagy is involved in cancer, infection, immunity, and inflammation and may be a potential therapeutic target. Increasing evidence has revealed that autophagy has primary implications for esophageal cancer, including its initiation, progression, tumor microenvironment (TME) modification, diagnosis, and treatment. Notably, autophagy displayed excellent application potential in radiotherapy combined with immunotherapy. Radiotherapy combined with immunotherapy is a new potential therapeutic strategy for cancers, including esophageal cancer. Autophagy modulators can work as adjuvant enhancers in radiotherapy or immunotherapy of cancers. This review highlights the most recent data related to the role of autophagy regulation in esophageal cancer.
Asunto(s)
Neoplasias Esofágicas , Neoplasias , Autofagia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/terapia , Humanos , Factores Inmunológicos/uso terapéutico , Inmunoterapia , Neoplasias/tratamiento farmacológico , Microambiente TumoralRESUMEN
OBJECTIVE: Dysregulation of feline leukemia virus subgroup C receptor 1(FLVCR1) expression has been investigated in several tumors. However, the expression and role of FLVCR1 in esophageal squamous cell carcinoma (ESCC) remain largely unknown. METHODS: FLVCR1 expression in tissues was measured by immunohistochemical staining (IHC). Celigo assay, MTT assay, colony formation, caspase 3/7 activity analysis, wound healing assay, Transwell migration, and invasion assay were applied to assess the effects of FLVCR1 on ESCC tumorigenesis. Coimmunoprecipitation (Co-IP) and liquid chromatography-mass spectrometry (LC-MS) were used to identify protein interactions with FLVCR1. An in vivo imaging system (IVIS) was used to investigate the functions of FLVCR1 on the growth and metastatic capability of ESCC cells in a xenograft model and a tail vein metastasis model. RESULTS: Elevated expression of FLVCR1 was detected in ESCC tissues and predicted poor survival. Upregulated FLVCR1 was positively correlated with lymph node metastasis (N stage) and late tumor-node-metastasis (TNM) stage. FLVCR1 knockdown inhibited cell proliferation and colony formation ability, induced cell apoptosis, and repressed cell migration and invasion of ESCC in vitro. Inhibition of FLVCR1 markedly repressed tumorigenicity and metastasis of ESCC cells in vivo. Mechanistically, chromosome segregation 1-like (CSE1L) was identified to interact with FLVCR1 using a Co-IP assay. Moreover, the inhibitory effect of FLVCR1 knockdown on proliferation and migration was counteracted by the exogenous expression of CSE1L. CONCLUSION: FLVCR1 plays a pivotal role in ESCC cell survival, growth, and migration. These functions may be partially dependent upon the protein interaction between FLVCR1 and CSE1L. In addition, FLVCR1 can be applied as a clinical prognostic marker for patients with ESCC.
RESUMEN
Objective: Our previous study suggested cyclin-dependent kinase-like 3 (CDKL3) acts as a new oncogene in esophageal squamous cell carcinoma (ESCC) cell line TE-1. However, the molecular mechanisms and biological effects of CDKL3 in ESCC remain unknown. In the present study, we aimed to explore the clinical significance of CDKL3 in ESCC and how CDKL3 regulates the malignant behavior of ESCC. Methods: ESCC samples were stained by immunohistochemical staining (IHC) and analyzed for the expression of CDKL3. The functions of CDKL3 on proliferation, apoptosis, migration, invasion, and colony formation were investigated by celigo assay, MTT assay, colony formation, caspase 3/7 activity analysis, transwell migration and invasion assay, respectively. A transplanted tumor model was established to study the functions of FLVCR1 on the tumorigenesis of ESCC cells. Microarray analysis was utilized to identify the CDKL3-regulated genes in ESCC cells. Results: ESCC tumor tissues possessed a significantly higher expression of CDKL3 and autophagy-related gene 5 (ATG5) than matched adjacent normal tissues. The high expressions of CDKL3 were positively associated with the tumor-node-metastasis (TNM) stage and Ki67. Upregulated ATG5 expression was positively correlated with male, advanced tumor (T) stage, and TNM stage. Kaplan-Meier analysis showed that ESCC patients with higher expression of CDKL3 or ATG5 had a shorter overall survival. The worst prognosis was recognized in patients with both high manifestations of CDKL3 and ATG5. Time-dependent receiver operating characteristic (ROC) curve was established to reveal that the combination of CDKL3, ATG5, and TNM stage-based model had better prognostic accuracy than TNM stage. Moreover, CDKL3 knockdown markedly repressed cell growth and aggressivity in vitro and in vivo. Mechanistically, ATG5 was confirmed as a downstream gene involved in the pro-oncogenic function of CDKL3. Conclusion: CDKL3 can be utilized as an independent poor prognostic marker in ESCC patients. Furthermore, CDKL3 may promote tumor profession, invasion, metastasis, and prohibit tumor apoptosis partly by ATG5 activation.
RESUMEN
Three-dimensional (3D) printing continuous carbon fiber-reinforced polylactic acid (PLA) composites offer excellent tensile mechanical properties. The present study aimed to research the effect of process parameters on the tensile mechanical properties of 3D printing composite specimens through a series of mechanical experiments. The main printing parameters, including layer height, extrusion width, printing temperature, and printing speed are changed to manufacture specimens based on the modified fused filament fabrication 3D printer, and the tensile mechanical properties of 3D printing continuous carbon fiber-reinforced PLA composites are presented. By comparing the outcomes of experiments, the results show that relative fiber content has a significant impact on mechanical properties and the ratio of carbon fibers in composites is influenced by layer height and extrusion width. The tensile mechanical properties of continuous carbon fiber-reinforced composites gradually decrease with an increase of layer height and extrusion width. In addition, printing temperature and speed also affect the fiber matrix interface, i.e., tensile mechanical properties increase as the printing temperature rises, while the tensile mechanical properties decrease when the printing speed increases. Furthermore, the strengthening mechanism on the tensile mechanical properties is that external loads subjected to the components can be transferred to the carbon fibers through the fiber-matrix interface. Additionally, SEM images suggest that the main weakness of continuous carbon fiber-reinforced 3D printing composites exists in the fiber-matrix interface, and the main failure is the pull-out of the fiber caused by the interface destruction.
RESUMEN
Cancer patients with different stages can benefit from radiotherapy, but there are still limited due to inherent or acquired radioresistance. The epithelial-mesenchymal transition (EMT) is a complex biological process that is implicated in malignant characteristics of cancer, such as radioresistance. Although the possible mechanisms of EMT-dependent radioresistance are being extensively studied, there is a lack of a clear picture of the overall signaling of EMT-mediated radioresistance. In this review, we highlight the role and possible molecular mechanisms of EMT in cancer radioresistance, in particular to EMT-associated signaling pathway, EMT-inducing transcription factors (EMT-TFs), EMT-related non-coding RNAs. The knowledge of EMT-associated mechanisms of radioresistance will offer more potent therapy targets to improve the radiotherapy responses.
Asunto(s)
Transición Epitelial-Mesenquimal/fisiología , Neoplasias/patología , Tolerancia a Radiación , Humanos , Transducción de Señal , Factores de TranscripciónRESUMEN
[This corrects the article .].
RESUMEN
BACKGROUND: Cyclin-dependent kinase-like 3 (CDKL3) is a putative protein serine kinase and plays an important role in the regulation of cell growth and/or differentiation. However, studies on the function of CDKL3 in esophageal squamous cell carcinoma (ESCC) is limited. In our study, we explored the role and prognosis of CDKL3 in ESCC and underlying mechanism. MATERIALS AND METHODS: The expression of CDKL3 was investigated by quantitative reverse transcription polymerase chain reaction and immunohistochemical staining. CDKL3 expression was downregulated by the RNAi-mediated knockdown. The functions of CDKL3 on cell growth were assessed by Celigo image cytometry, MTT assay, cell-cycle analysis, Annexin V assay, and caspase-3/7 activity analysis. The effect of CDKL3 on cellular invasive was investigated by the Transwell assay. Pathscan Stress Signaling Antibody Array was used to study the underlying mechanism. Additionally, the association between the survival and CDKL3 expression in ESCC were evaluated based on the TCGA data. RESULTS: CDKL3 was highly expressed in ESCC tissues and cell lines. TE-1 cells transfected with CDKL3-shRNA-lentivirus significantly decreased CDKL3 expression and resulted in inhibiting cell proliferation, inducing the S-phase cell-cycle arrest, attenuating cellular invasive and increasing cell apoptosis. The expression of pERK1/2, p-Akt, p-Smad2, p-p38 mitogen-activated protein kinase, cleaved caspase-7, and phospho-Chk1 were significantly decreased by CDKL3 knockdown. In addition, high expression of CDKL3 was associated with shorter overall survival. CONCLUSION: Our findings suggest that higher expression of CDKL3 is correlated with poor prognosis in patients with ESCC and play a vital role in the malignant phenotype of ESCC cell lines, which indicating that CDKL3 may be as a new therapeutic target in ESCC.
RESUMEN
Cancer related inflammation (CRI) plays an important role in the development of esophageal cancer (EC), and the target gene analysis shows that miR-302b potential target genes closely correlated to CRI important signaling pathways. The present study was to evaluate the inhibition of miR-302b on CRI in EC and its mechanism. We found that the expression levels of miR-302b in EC cells were lower than that in Het-1A cells, while TE11 with the lowest expression and OE33 with the highest. Inflammatory stimuli at 48 h significantly reduced expression of miR-302b in EC cells, but had no effect in Het-1A. After up-regulation of miR-302b in TE11 and down-regulation of miR-302b in OE33, it was found that miR-302b reduced CRI key transcription factors and representative cytokines. Then, over-expressed of miR-302b significantly altered potential target genes protein expressions and there was a negative correlation between miR-302b and potential target genes protein expressions (ERBB4, IRF2 and CXCR4) in EC tissues. Then reporter gene analysis revealed that miR-302b post-transcriptionally regulated expression of target genes by specific area of 3'-UTR. Transfected by target genes shRNA plasmids together could get the same effects of miR-302b on protein expression of CRI key transcription factors. Furthermore, miR-302b was able to repress tumor growth and transcription factors protein expression in vivo. These finding suggests that miR-302b inhibits key transcription factors and cytokines by targeting ERBB4, IRF2 and CXCR4, implicating its role in the inhibition of CRI in EC.
Asunto(s)
Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/genética , Inflamación/complicaciones , Inflamación/genética , Factor 2 Regulador del Interferón/genética , MicroARNs/genética , Receptor ErbB-4/genética , Receptores CXCR4/genética , Regiones no Traducidas 3' , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Biología Computacional/métodos , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Inflamación/patología , Interferencia de ARNRESUMEN
BACKGROUND: Increasing evidence indicates that radioresistance remains a major problem in the treatment of patients with esophageal squamous cell carcinoma (ESCC). This study was designed to investigate the expression of microRNA-381 (miR-381) and its function in the radioresistance of ESCC. METHODS: In this study, miR-381 expression was first detected in ESCC cell lines and tissue samples by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the effects of miR-381 expression on growth, apoptosis, and radiosensitivity of ESCC cells were analyzed by MTT, colony formation, and flow cytometry, respectively. Dual-luciferase reporter assays were performed to validate the regulation of a putative target of miR-381, in corroboration with qRT-PCR and Western blotting assays. RESULTS: ESCC cell lines or tissues were found to express significantly lower miR-381 than normal esophageal epithelial cells or adjacent normal tissues, respectively. Ectopic expression of miR-381 in ESCC cell lines blocked proliferation, reduced colony formation, enhanced apoptosis, and increased radiosensitivity by enhancing irradiation-induced apoptosis. In addition, dual-luciferase reporter assays showed that miR-381 binds to the 3'-untranslated region of X-linked inhibitor of apoptosis protein (XIAP), suggesting that XIAP should be a direct target of miR-381. Re-expression of miR-381 suppressed XIAP protein expression in ESCC cells, and the effects of miR-381 upregulation on ESCC cells were found to be similar with silencing of XIAP. In addition, XIAP mRNA expression significantly increased in ESCC tissues and was inversely correlated with miR-381 expression. CONCLUSION: The results of this study suggest that miR-381/XIAP pathway contributed to the growth inhibition, increase in apoptosis, and enhancement of radiosensitivity in ESCC cells Therefore, miR-381 may be a potential therapeutic target in human ESCC.
RESUMEN
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Chemoresistance occurrence is a major cause of treatment failure in HCC. Currently, extensive research has revealed diverse mechanisms for chemoresistance, but the molecular mechanisms underlying the role of miRNAs in resistance to 5-FU are not confirmed in HCC cells. By quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we found that miR-144 was significantly decreased in HCC cell lines. It has been further demonstrated that miR-144 were significantly down-regulated in Bel-7402/5-FU cells compared with parental Bel-7402 cells by qRT-PCR and western blot. The expression of Nrf2 was reversely correlated to that of miR-144 in HCC cells. Moreover, Enhancement of 5-FU-induced cytotoxicity and apoptosis are resulted from the transfection with miR-144 mimics in Bel-7402/5-FU cells. Mechanically, miR-144 promoted nuclear factor erythroid-2-related factor-2 (Nrf2) mRNA degradation by directly targeting the Nrf2 3'untranslated region (3'UTR). In addition, ectopic expression of miR-144 in Bel-7402/5-FU cells reduced the levels of Nrf2 and inhibited the transcription of Nrf2-dependent HO-1 gene, thus contributing to 5-FU sensibilization. Conversely, re-expression of Nrf2 partly attenuated the chemosensibilization of miR-144. Our study showed that miR-144 serves as a potential chemoresistance-reversal agent in hepatocellular carcinoma cells, which is at least partly due to the down-regulation of Nrf2-dependent antioxidant pathway.
RESUMEN
BACKGROUND: Radiation resistance poses a major clinical challenge in treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms of radioresistance has not been fully elucidated. Since accumulating evidence demonstrates that aberrant expression of microRNAs (miRNAs) contributes to cancer sensitivity to radiation, we aimed to identify miRNAs associated with radioresistance of ESCC. METHODS: In this study, we used GeneChip miRNA Array to perform an comparison of miRNAs expression in tissues from primary ESCC and recurrent ESCC in situ after radiotherapy. Differential expressions of miRNAs were comfirmed by quantitative Real-Time PCR in tissues and six ESCC cell lines. Cell radiosensitivity were determined by colony formation assay. Functional analyses of miRNA-381 in ESCC cells growth and metastasis were performed by MTT and Transwell Assays. In vivo assays of the functions of miRNA-381 were performed in tumor xenografts. RESULTS: One miRNA candidate, miRNA-381, was found to be downregulated in radiation resistance tissues and cells. Enforced expression of miRNA-381 increased radiosensitivity of ESCC cells and promoted nonaggressive phenotype including decreased cellular proliferation and migration. In contrast, inhibition of miRNA-381 in ESCC cells promoted radiation resistance and development of an aggressive phenotype. In vivo assays extended the significance of these results, showing that miRNA-381 overexpression decreased the tumor growth and the resistance to radiation treatment in tumor xenografts. CONCLUSIONS: Together, our work reveals miRNA-381 expression as a critical determinant of radiosensitivity in esophageal cancer cells.
RESUMEN
OBJECTIVE: To investigate the role of miR-520a in regulation ErbB4 expression and the biological behavior of esophageal squamous cell carcinoma (ESCC). METHODS: The role of miR-520a in regulating the expression of ErbB4 was investigated by Western blotting and luciferase reporter assay system. The effect of miR-520a on the proliferation and invasion of ESCC cells was detected by MTT and Transwell invasion assay, respectively. RESULTS: Western blotting and luciferase reporter assay revealed that miR-520a down-regulated the expression of ErbB4 in vitro. miR-520a significantly inhibited the proliferation and suppressed the invasion of ESCC cell line Eca109. CONCLUSION: miR-520a regulates the expression of ErbB4 and suppresses the proliferation and invasion of ESCC cells in vitro, suggesting its role as a tumor suppressor.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Proliferación Celular , Neoplasias Esofágicas/metabolismo , MicroARNs/metabolismo , Receptor ErbB-4/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , HumanosRESUMEN
BACKGROUND: ErbB4 expression has been noted in various tumors, but its regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to investigate whether miR-302b regulates the expression of ErbB4 at the post-transcriptional level and to determine its expression, significance, and function in ESCC. METHODS: We used real-time reverse transcriptase-polymerase chain reaction to quantify the expression of miR-302b in 50 ESCC tissues and analyzed its relationship with clinicopathological factors and survival. Then, we investigated the post-transcriptional regulation of ErbB4 expression using immunoblot analysis and luciferase reporter assays. Finally, the effects of miR-302b on proliferation, apoptosis, and invasion of ESCC cells was detected using MTT, flow cytometric analysis, and transwell invasion assays, respectively. RESULTS: miR-302b was significantly down-regulated and correlated with tumor differentiation and lymph node metastasis in ESCC. Univariate and multivariate analyses indicated that low miR-302b expression might be a poor prognostic factor. Further studies demonstrated that miR-302b post-transcriptionally down-regulated the expression of ErbB4 in vitro. Moreover, miR-302b inhibited proliferation by inducing apoptosis and repressed invasion in the ESCC cell lines. CONCLUSIONS: miR-302b is a potential molecular marker of ESCC and functions as a tumor suppressor by post-transcriptionally regulating ErbB4.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Receptores ErbB/genética , Neoplasias Esofágicas/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Movimiento Celular , Supervivencia sin Enfermedad , Receptores ErbB/metabolismo , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica , Modelos de Riesgos Proporcionales , Interferencia de ARN , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor ErbB-4 , Estudios Retrospectivos , Proteínas Supresoras de TumorRESUMEN
BACKGROUND: X-chromosome-linked IAP (XIAP) and nuclear factor-κB (NF-κB) are frequently overexpressed and correlate closely with chemoradiotherapy resistance and poor prognosis in many cancers. However, the significance of XIAP and NF-κB expression in radiotherapy sensitivity and its effect on the prognosis of esophageal squamous cell carcinoma (ESCC) are still unknown. The aim of this study was to examine XIAP and NF-κB status in ESCC patients undergoing postoperative radiotherapy after radical surgery, and to evaluate their clinical significance. METHODS: A total of 78 ESCC patients treated with postoperative radiotherapy after radical surgery were enrolled in this study. We immunohistochemically investigated the expression of XIAP and NF-κB in tissues from enrolled patients with specific antibodies. Then, the correlations among XIAP, NF-κB expression, clinicopathological features and its prognostic relevance in ESCC were analyzed. RESULTS: The increased expression of XIAP and NF-κB in ESCC tissues were clearly correlated with the tumor differentiation and p-TNM stage. Significant positive correlations were found between the expression status of XIAP and NF-κB (r = 0.779, P = 0.000). Overexpression of XIAP and NF-κB and metastasis were significantly associated with shorter overall survival times in univariate analysis (P < 0.05). Multivariate analysis also confirmed that XIAP expression was an independent prognostic factor (P = 0.005). CONCLUSIONS: XIAP and NF-κB are intensively expressed in ESCC. The level of XIAP is positively correlated to progression and prognosis of ESCC.
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , FN-kappa B/metabolismo , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
Radiation therapy can effectively kill cancer cells through ROS generation. Cancer cells with upregulated antioxidant systems can develop high radioresistance ability, and the transcription factor NF-E2-related factor 2 (Nrf2) is a key regulator of the antioxidant system. Currently, there are numerous data indicating the important role of Nrf2 in cancer radioresistance. In this review, we summarize the aberrant regulation of Nrf2 in radioresistant cells and discuss the effects and underlying mechanism of Nrf2 in promoting radioresistance. These findings suggest that Nrf2 might be a potential therapeutic target in cancer radiation resistance or a promising radioprotector for normal organs during radiation therapy in the future.
Asunto(s)
Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Tolerancia a Radiación/genética , Animales , Antioxidantes/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias/radioterapia , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Fármacos Sensibilizantes a Radiaciones/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: To evaluate the potential efficacy of preventive effect of ulinastatin in esophagectomy patients. METHODS: Eighty patients with esophageal cancer were preoperatively allocated at random into two equal groups. Ulinastatin was administered to the treatment group (U) whereas the control group (C) received a placebo. The arterial oxygen tension and carbon dioxide tension were measured and the respiratory index (RI) was calculated. Plasma levels of circulating T lymphocyte subsets and interleukin 6 (IL-6) were measured and clinical courses of patients in the two groups were compared. RESULTS: RI in the U group was significantly lower than that in the C group. The rate of postoperative complications and the duration of ICU stay were significantly lower in the U group. Ulinastatin significantly increased the rate of CD3+ and CD4+ cells, and ratio of CD4+/CD8+, but decreased the rate of CD8+ cells and release of IL-6 compared to the C group on postoperative days 1 and 3. Patients within the C group showed worse recurrence free survival. Multivariate analysis revealed that ulinastatin administration significantly decreased the incidence of recurrence. CONCLUSIONS: Ulinastatin had a preventive effect on postoperative complications and immunosuppression in esophagectomy patients, thereby prolongingrecurrence free survival.
Asunto(s)
Neoplasias Esofágicas/tratamiento farmacológico , Esofagectomía/efectos adversos , Glicoproteínas/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Complicaciones Posoperatorias/prevención & control , Subgrupos de Linfocitos T/efectos de los fármacos , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Dióxido de Carbono/metabolismo , Estudios de Casos y Controles , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Esofagectomía/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Terapia de Inmunosupresión , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Oxígeno/metabolismo , Pronóstico , Mecánica Respiratoria , Tasa de Supervivencia , Inhibidores de Tripsina/uso terapéutico , Adulto JovenRESUMEN
Esophageal cancer (EC) is the ninth most common malignancy with a poor prognosis. It is clear that improvements need to be made to reveal the exact molecular mechanisms of EC. Cancer-related inflammation (CRI) recently has been proposed as a major physiological hallmark of malignancy and has important value in diagnosis, treatment, and prognosis. But the role of CRI in EC has remained unclear. In this review, we focus primarily on the function of key mediators of CRI in EC, including transcription factors, chemokines, cytokines, reactive oxygen species, COX-2, and specific microRNAs. Through a comprehensive analysis, we try to reveal the interaction between CRI and EC, providing novel preventive, diagnostic, and therapeutic strategies to reduce the health burden of EC.
Asunto(s)
Quimiocinas/metabolismo , Citocinas/metabolismo , Neoplasias Esofágicas/patología , Inflamación/patología , Factores de Transcripción/metabolismo , Ciclooxigenasa 2/metabolismo , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/metabolismo , Humanos , Inflamación/complicaciones , Inflamación/metabolismo , MicroARNs/metabolismo , Pronóstico , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Acquired resistance to 5-fluorouracil (5-FU) is a serious therapeutic obstacle in advanced hepatocellular carcinoma (HCC) patients. AIM: To investigate whether nuclear factor erythroid 2-related factor 2 (Nrf2) was associated with drug resistance in 5-FU resistant Bel-7402 (Bel-7402/5-FU) cells, and if sorafenib, an oral multikinase inhibitor targeting the tumor and vasculature, could reverse drug resistance in Bel-7402/5-FU cells at the noncytotoxic dosage. METHODS: We used MTT to detect the resistance reversal activity of sorafenib, compared Nrf2 expression in various conditions by western blot and qRT-PCR, and analyzed subcellular localization of Nrf2 by immunofluorescence. RESULTS: The endogenous expression of Nrf2 in Bel-7402/5-FU cells was similar to that observed in Bel-7402 cells. However, Nrf2 expression levels were increased by 5-FU treatment in Bel-7402/5-FU cells higher than that in Bel-7402 cells, which is to highlight the Nrf2 contribution to the enhanced resistance of Bel-7402/5-FU cells to 5-FU. Moreover, intracellular Nrf2 protein level was significantly down-regulated by Nrf2-shRNA in Bel-7402/5-FU cells, resulting in partial reversal of 5-FU resistance. Sorafenib down-regulated the increased expression of Nrf2 induced by 5-FU treatment and partly reversed 5-FU resistance in Bel-7402/5-FU cells. CONCLUSIONS: These results suggested that more sensitive cell defense mediated by Nrf2 was associated with drug resistance of Bel-7402/5-FU cells. Sorafenib reversed drug resistance, and its reversal mechanism might be due to the suppression of Nrf2 expression induced by 5-FU, indicating the feasibility of using Nrf2 inhibitors to increase efficacy of chemotherapeutic drugs in HCC patients.