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OBJECTIVE: This study aimed to investigate the effect of preoperative albumin-to-globulin ratio (AGR) on overall survival (OS) and health-related quality of life in patients with esophageal cell squamous carcinoma (ESCC). METHODS: Serum albumin and globulin were measured within one week before surgery. Multiple follow-ups were conducted among patients with ESCC in the study in order to assess their life quality. The method used in the study was a telephone interview. Quality of life was measured using the EORTC Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30, version 3.0) and Esophageal Cancer Module (EORTC QLQ- OES18). RESULTS: A total of 571 ESCC patients were included in the study. The results illustrated that 5-year OS of high AGR group (74.3%) was better than the low one (62.3%) (P = 0.0068). Univariate and multivariate Cox regression analysis found that preoperative AGR (HR = 0.642, 95%CI: 0.444-0.927) are prognostic factor for patients with ESCC after surgery. In terms of quality of life, found that low AGR associated with increased postoperative time to deterioration (TTD) events in ESCC patients, and compared to low AGR, high AGR could delay the deterioration of emotional functioning(P = 0.001), dysphagia(P = 0.033), trouble with taste(P = 0.043) and speech problems(P = 0.043). After using the multivariate Cox regression analysis showed that high AGR could improve patients' emotional function (HR = 0.657, 95% CI: 0.507-0.852) and trouble with taste (HR = 0.706, 95% CI: 0.514-0.971). CONCLUSIONS: Preoperative AGR in patients with ESCC after esophagectomy was positively correlated with overall survival rate and quality of life after operation.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Globulinas , Humanos , Calidad de Vida , Estudios Prospectivos , Carcinoma de Células Escamosas de Esófago/cirugía , Neoplasias Esofágicas/patología , Albúmina Sérica/análisis , Globulinas/análisis , Estudios Retrospectivos , PronósticoRESUMEN
BACKGROUND AND OBJECTIVE: Recent advancements in immunotherapy led to the development of Chimeric antigen receptor (CAR) T-cell therapy. CAR-T cell therapy in non-small cell lung cancer (NSCLC) is hindered by overexpression of transforming growth factor (TGFß) in the cancer cells that have a negative regulatory role on T-cells activity. This study characterized CAR-T with overexpression of mothers against decapentaplegic homologue 7 (SMAD), a negative regulator of TGFß downstream signalling. METHODS: We have generated three types of CAR-T: epidermal growth factor receptor (EGFR)-CAR-T, EGFR-dominant-negative TGFbeta receptor 2 (DNR)-CAR-T, and EGFR-SMAD7-CAR-T by transducing human T-cells with the lentivirus constructs. We characterized the proliferation, expression of proinflammatory cytokines, activation profile, and lysis capacity in co-cultures with A549 lung carcinoma cells with and without TGFß neutralizing antibodies. We also tested the therapeutic potential of EGFR-SMAD7-CAR-T in the A549 cells tumour-bearing mice model. RESULTS: Both EGFR-DNR-CAR-T and EGFR-SMAD7-CAR-T demonstrated a higher proliferation rate and lysis capacity to A549 than traditional EGFR-CAR-T. Neutralization of TGFß by the antibodies resulted in increased performance of EGFR-CAR-T. In vivo, both EGFR-DNR-CAR-T and EGFR-SMAD7-CAR-T resulted in complete tumour resorption by day 20, whereas conventional CAR-T only has a partial effect. CONCLUSION: We demonstrated the high efficacy and resistance to negative TGFß regulation of EGFR-SMAD7-CAR-T comparable with EGFR-DNR-CAR-T and without the systemic effect of TGFß inhibition.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Receptores Quiméricos de Antígenos , Humanos , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Receptores Quiméricos de Antígenos/metabolismo , Receptores ErbB/metabolismo , Linfocitos T/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Línea Celular Tumoral , Proteína smad7/genética , Proteína smad7/metabolismoRESUMEN
Meta-analysis was performed on the Web of Science, PubMed, Embase, and Cochrane databases to evaluate the effect of epidermal growth factor receptor (EGFR) mutation status on programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors, and the association between EGFR mutation status and PD-L1 expression in non-small cell lung cancer (NSCLC) patients. Pooled effect (hazard ratio/odds ratio, HR/OR) with 95% confidence interval (CI) was calculated, and the source of heterogeneity was explored by subgroup analysis and meta-regression using Stata/SE 15.0. Meta-analysis of the association between EGFR mutation status and overall survival (OS) in NSCLC with immunotherapy was calculated from four randomized controlled trials. We found that immune checkpoint inhibitors significantly prolonged OS over docetaxel overall (HR 0.71, 95% CI 0.64-0.79) and in the EGFR wild type (HR = 0.67, 95% CI = 0.60-0.75), but not in the EGFR mutant subgroup (HR = 1.11, 95% CI = 0.80-1.52). Meta-analysis of the association between EGFR mutation status and PD-L1 expression in NSCLC included 32 studies. The pooled OR and 95% CI were 0.60 (0.46-0.80), calculated by random effects model. No source of heterogeneity was found in subgroup analysis. Sensitivity analysis was carried out with a fixed model, and the influence of a single study on the pooled results showed no significant change with robust meta-analysis methods. Harbord's weighted linear regression test (P = 0.956) and Peters regression test (P = 0.489) indicated no significant publication bias. The limited benefit of single-agent PD-1/PD-L1 inhibitors in the second-line or later setting for EGFR-mutated NSCLC may be partly due to the lower expression of PD-L1.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutación , Receptor de Muerte Celular Programada 1RESUMEN
PURPOSE: This study aimed to explore the role and underlying mechanism of action of Endoplasmic reticulum oxidoreductin-1 L (ERO1L) in lung adenocarcinoma (LUAD). MATERIALS AND METHODS: The Gene expression profiling interactive analysis database was used to analyze the expression of ERO1L in LUAD cases. The expression of ERO1L and Wnt2 in LUAD tissue was evaluated using immunohistochemistry. We also used western blotting to assess the expression of ERO1L or Wnt2 and the phosphorylation of ß-catenin in LUAD cell lines. Plasmid transfection and small interfering RNA were used for overexpression and knockdown of ERO1L in LUAD cells, respectively. The proliferation, invasion and migration of LUAD cells were analyzed using cell viability, Transwell invasion and wound healing assays. The growth of LUAD tumors in animal models was assessed using tumor xenograft experiments. RESULTS: This study revealed that elevated ERO1L expression was associated with a poor prognosis in LUAD patients. In addition, ERO1L expression was significantly associated with lymph-node metastasis, TNM stage and tumor size. The expression of Wnt2 was positively associated with ERO1L expression in LUAD tissue samples and cell lines. ERO1L overexpression upregulated the expression of Wnt2 and ß-catenin phosphorylation in vitro. Additionally, ERO1L was essential for the ubiquitination of Wnt2. Last, ERO1L promoted the proliferation and metastasis of LUAD via the Wnt2 signaling pathway in vitro and in vivo. CONCLUSION: These findings suggest that ERO1L was highly expressed in LUAD tissue, and it promoted the proliferation and metastasis of LUAD by activating the Wnt2/ß-catenin signaling pathway.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Glicoproteínas de Membrana/metabolismo , Oxidorreductasas/metabolismo , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Retículo Endoplásmico/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Transducción de Señal , Proteína wnt2/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
BACKGROUND: To investigate the effect of tea consumption on the improvement of postoperative quality of life in male patients with esophageal squamous cell carcinoma (ESCC). METHODS: The quality of life information of 290 male patients with ESCC was collected. The time to deterioration and the number of events in each area of quality of life was calculated by time-to-deterioration (TTD) model. The association between postoperative tea drinking and postoperative quality of life in male ESCC patients was investigated using the Cox proportional risk model. RESULTS: Postoperative tea-drinking patients experienced delayed TTD in multiple domains, including general health, physical, role, emotional, and cognitive function, fatigue, nausea and vomiting, dyspnea, loss of appetite, constipation, diarrhea, eating problems, difficulty swallowing, choking while swallowing saliva, dry mouth, taste difficulties, coughing, and speech problems. The multivariate Cox regression analysis showed that drinking tea after surgery improved quality of life, including physical function (HR = 0.722, 95% CI: 0.559-0.933), role function (HR = 0.740, 95% CI: 0.557-0.983), eating problems (HR = 0.718, 95% CI: 0.537-0.960), odynophagia (HR = 0.682, 95% CI: 0.492-0.945), trouble swallowing saliva (HR = 0.624, 95% CI: 0.444-0.877), coughing (HR = 0.627, 95% CI: 0.442-0.889) and speech problems (HR = 0.631, 95% CI: 0.441-0.903). Furthermore, the improvement was more significant in patients who drank tea before surgery and continued to drink tea after surgery. CONCLUSIONS: Postoperative tea drinking had a positive effect on delay in clinical deterioration and improvements in multiple functions and symptoms associated with ESCC in men.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Masculino , Carcinoma de Células Escamosas de Esófago/inducido químicamente , Calidad de Vida , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/inducido químicamente , Té/efectos adversos , Periodo PosoperatorioRESUMEN
AarF domain containing kinase 5 (ADCK5) is a member of an atypical kinase family and overexpressed in many carcinomas including lung cancer, while the function of this protein has not been elucidated. Here we investigated the mechanism of ADCK5 involved in regulating invasion and migration of lung cancer cells, and showed that ADCK5 might regulate the expression of tumor oncogene human pituitary tumor transforming gene-1 (PTTG1) by phosphorylating transcription factor SOX9, therefore enhancing the migration and invasion capabilities of lung cancer cells. Mutagenesis of potential serine phosphorylation sites on SOX9 indicated that serine 181 might be required to maintain transcription activation of SOX9 as well as increase PTTG1 levels. The serine 181 site of SOX9 is in a motif that is targeted by ADCK5. The ADCK5-SOX9-PTTG1 pathway might be a potential therapeutic target for lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Movimiento Celular/genética , Neoplasias Pulmonares/patología , Proteínas Serina-Treonina Quinasas/fisiología , Factor de Transcripción SOX9/genética , Securina/genética , Células A549 , Carcinoma de Pulmón de Células no Pequeñas/genética , Adhesión Celular/genética , Proliferación Celular/genética , Células Cultivadas , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Invasividad Neoplásica/genética , Metástasis de la Neoplasia , Proteínas Serina-Treonina Quinasas/genética , Factor de Transcripción SOX9/metabolismo , Securina/metabolismo , Transducción de Señal/genéticaRESUMEN
PURPOSE: The aims of this study were to review the surgical experience and evaluate the feasibility of thoracoscopic total laryngo-pharyngo-oesophagectomy by multidisciplinary team in the patients with pharyngoesophageal junction cancer. METHODS: A total of 31 patients with pharyngoesophageal junction cancer who underwent thoracoscopic total laryngo-pharyngo-oesophagectomy with gastric pull-up reconstruction performed by a collaborative thoracic surgery and otolaryngology surgery team in our department from January 2009 to January 2019 were retrospectively analysed. Surgical experience, Postoperative morbidity, overall survival were evaluated. RESULTS: The median age was 62 years old. Among these patients, 20 had hypopharyngeal cancer, 11 had cervical oesophageal cancer. No patients died during the perioperative period, and the median operation time was 4 h 30 min. The mean hospital stay was 13 days. The rate of complications was 32.3%. There were two cases of anastomotic leakage, four cases of moderate pulmonary infection. The median follow-up period was 31 months. Four patients were lost to follow-up in the second and fourth years and were considered to have died at that time. The 3- and 5-year overall survival rates were 52.6% and 31.6%, respectively. CONCLUSION: As a salvage surgery, thoracoscopic total laryngo-pharyngo-oesophagectomy by multidisciplinary team can be performed with an acceptable level of perioperative morbidity and mortality, relatively good recovery, and acceptable survival outcome for patients with pharyngoesophageal junction cancer.
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Neoplasias Esofágicas , Esofagectomía , Neoplasias Esofágicas/cirugía , Humanos , Persona de Mediana Edad , Grupo de Atención al Paciente , Faringectomía , Estudios RetrospectivosRESUMEN
BACKGROUND: This case-control study investigated the role of Chlamydia pneumoniae (Cpn) infection in the pathogenesis of lung cancer and the combined and interaction effect of Cpn infection, smoking, and various environmental factors. METHODS: The study comprised 449 lung cancer patients and 512 age- and sex-matched healthy controls. All participants provided a 5 ml fasting peripheral venous blood sample for testing Cpn-specific IgG and IgA by using micro-immunofluorescence. Besides analyzing the associations between Cpn and lung cancer, combined effect analysis, logistic regression, and the Excel table made by Andersson were used to analyze the combined and interaction effects of Cpn and environmental factors on lung cancer. RESULTS: Compared to those with no evidence of serum Cpn IgA or Cpn IgG, those with both Cpn IgG+ and IgA+ had 2.00 times the risk (95% CI: 1.34-3.00) of developing lung cancer. Cpn IgG+ or IgA+ was associated with a significantly increased risk of lung cancer among smokers; the adjusted odds ratio (OR) was 1.79 (95% CI: 1.10-2.91) and 2.27 (95% CI: 1.38-3.72), respectively. Those exposed to passive smoking with Cpn IgG+ or IgA+ also showed an increased risk of lung cancer; the adjusted OR was 1.82 (95% CI: 1.20-2.77) or 1.87 (95% CI: 1.22-2.87), respectively. Similar results were also observed among alcohol drinkers. Multiplicative and additive interactions were not observed between Cpn infection and environmental factors. The combined effects of Cpn IgG+ or IgA+ with smoking, passive smoking, and family history of cancer on lung cancer were determined. CONCLUSION: Cpn infection is potentially associated with primary lung cancer in the Chinese Han population and has combined effects with smoking, passive smoking, and family history of cancer.
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Infecciones por Chlamydophila/patología , Neoplasias Pulmonares/microbiología , Neoplasias Pulmonares/patología , Fumar/patología , Anciano , Estudios de Casos y Controles , China/epidemiología , Infecciones por Chlamydophila/epidemiología , Femenino , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Fumar/efectos adversos , Fumar/epidemiologíaRESUMEN
Aim: To investigate the expression and prognostic value of KRT 15 in esophageal carcinoma. Materials & methods: The expression levels of KRT 15 were measured in 128 cases of esophageal carcinoma and matched adjacent normal tissues by immunohistochemistry and Western blot assays. Results & conclusion: Western blot analysis shown the expression levels of KRT 15 in esophageal carcinoma were significantly higher compared with those in matched adjacent normal tissues (p < 0.001). immunohistochemistry result shown the high-expression rate of KRT 15 in esophageal carcinoma were 56.3%, which was significantly higher than those in normal tissues (35.9%; p = 0.002). KRT 15 high-expression correlated with T stage, lymph node metastasis, tumor node metastasis stage and prognosis (p < 0.05). These data indicate KRT 15 as a prognostic biomarker is highly expressed in esophageal carcinoma.
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Biomarcadores de Tumor , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidad , Expresión Génica , Queratina-15/genética , Adulto , Anciano , Neoplasias Esofágicas/diagnóstico , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Queratina-15/metabolismo , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Curva ROCRESUMEN
BACKGROUND: The present standard of surgical treatment for esophageal cancer is country dependent. The aim of the present study was to investigate the basic aspects of surgical procedures performed for esophageal cancer, and provide information about the present state of esophageal cancer surgery in China. METHODS: Data were obtained from a database administered by the Chinese Ministry for Health. A total of 542 participating hospitals were divided into seven geographic areas, and 10% of hospitals in each area were randomly chosen for inclusion. All patients with esophageal cancer, who underwent esophagectomy in these participating hospitals from January 1 to December 31, 2015, were included in the present study. The clinical characteristics, stage of tumor at diagnosis, operation summary and outcomes, and histological findings of patients were extracted and analyzed. RESULTS: The present study included 11,791 patients, and the average number of patients per hospital was 218. Squamous cell carcinoma was the most common pathological type, while the mid-esophagus was the most common location. Open procedures were performed in 63.8% of patients, while minimally invasive esophagectomy was performed in 36.2% of patients. Multiple approaches to transthoracic esophagectomy were utilized. Two-field lymphadenectomy was the most frequently performed (64.8%), followed by three-field lymphadenectomy (21.8%). Gastric tubes, thoracic duct ligation and postoperative enteral nutrition were implemented to minimize complications. CONCLUSION: The standard operative procedure and detailed technique for esophageal carcinoma surgery is presently being debated in China. This survey provides some basic information about the present state of esophageal cancer surgery countrywide.
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Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Escisión del Ganglio Linfático/métodos , Anciano , China , Bases de Datos Factuales , Nutrición Enteral , Esofagectomía/efectos adversos , Femenino , Humanos , Escisión del Ganglio Linfático/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Video-assisted thoracoscopic lobectomy with lymphadenectomy is considered one of the most effective treatments for early non-small cell lung cancer. We developed a novel approach for lobectomy in patients with right upper lung cancer through simplified synchronous disconnection of pulmonary arteries and veins. This study aimed to evaluate the feasibility, efficacy, safety, and cost-effectiveness of this minimally invasive technique in managing right upper lobectomy. PATIENTS AND METHODS: From March 2016 to September 2017, 62 patients with right upper lung cancer underwent lobectomy via simplified synchronous disconnection of pulmonary arteriovenous by video-assisted thoracoscopic surgery. All patients were followed up for 6-12 months after the procedure through clinic visits or telephone/e-mail interviews. RESULTS: Of the 62 patients (mean age, 57.2 ± 8.7 years), 28 were men (45.2%) and 34 (54.8%) were women. All procedures were successfully performed by thoracoscopy, with a mean operating time of 66.2 ± 9.0 min. The mean blood loss was 40.3 ± 19.5 mL. Only 1 (1.61%) patient required blood transfusion. The mean number of endoscopic linear stapling devices used was 2.6 ± 0.7. The mean number of lymph nodes harvested was 16.0 ± 1.6. Postoperative pneumonia was encountered in 4 (6.45%) patients. There was no postoperative mortality. The mean length of hospital stay was 5.3 ± 1.3 days. Six-month follow-up revealed an excellent clinical result and degree of satisfaction. CONCLUSIONS: Simplified synchronous disconnection of pulmonary arteries and veins is a feasible, economical, safe, and effective therapeutic procedure for right upper lung carcinoma. This novel procedure shows promise as a viable surgical approach for right upper lobectomy.
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Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Arteria Pulmonar/patología , Cirugía Torácica Asistida por Video , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Tempo Operativo , Resultado del TratamientoRESUMEN
BACKGROUND: Long-term survival of patients following liver transplantation can be achieved by application of genetically modified, immune tolerogenic immature dendritic cells (imDCs) to overcome allograft-induced acute cellular rejection, a major cause of death. In this study, using a rat model of liver transplantation, we determined whether cotransfection of transforming growth factor ß1 (TGF-ß1) and Fas ligand (FasL) in imDCs synergistically enhances immune tolerance. MATERIALS AND METHODS: We first determined the immune tolerogenic effects of TGF-ß1 and FasL independently or together in imDCs by measuring the levels of CD86 and CD80 and by assessing T-cell proliferation using mixed lymphocyte reaction tests. Next, a rat model of liver transplantation, in which dark agouti and Lewis rats treated with DCs exogenously expressing TGF-ß1 and/or FasL served as donors and recipients, respectively, was used to examine TGF-ß1/FasL-induced immune tolerance. Specifically, we assessed the Banff rejection activity index (RAI), liver functions (alanine transaminase and total bilirubin levels), serum levels of interleukin (IL)-1, IL-10, and IL-12, apoptosis by TUNEL, and posttransplant survival. RESULTS: TGF-ß1/FasL cotransfection of imDCs resulted in greater reduction of CD85 and CD80 expression and T-cell proliferation than a monotransfection. Cotransfected imDCs also showed reduced RAI scores, decreased plasma alanine transaminase and total bilirubin, altered cytokine levels, increased apoptosis, and prolonged survival than monotransfected imDCs in liver-allografted rats. CONCLUSIONS: By enhancing immune tolerance, reducing liver damage, and achieving long-term postsurgery survival, TGF-ß1/FasL cotransfection of imDCs may prove more beneficial for patients undergoing liver transplantation.
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Células Dendríticas/metabolismo , Proteína Ligando Fas/genética , Rechazo de Injerto/prevención & control , Tolerancia Inmunológica , Factor de Crecimiento Transformador beta1/genética , Animales , Apoptosis , Células Cultivadas , Proteína Ligando Fas/metabolismo , Técnicas de Transferencia de Gen , Inmunofenotipificación , Interleucinas/sangre , Hígado/patología , Trasplante de Hígado , Masculino , Ratas Endogámicas Lew , Linfocitos T/fisiología , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Dendritic cells transfected with interleukin (IL)-10 and transforming growth factor-ß1 (TGF-ß1) enhance T cell immunity and tolerance. However, no quantitative studies have investigated the suppressive functions of immature dendritic cells (imDC) cotransfected with IL-10 and TGF-ß1. The effects of imDC cotransfected with IL-10 and TGF-ß1 (IL-10-TGF-ß1-imDC) on immune tolerance induction in a rat transplantation model were investigated. In addition, effects of IL-10-TGF-ß1-imDC relative to IL-10-transfected imDC (IL-10-imDC) and TGF-ß1-transfected imDC (TGF-ß1-imDC) were compared. The infusion of IL-10-TGF-ß1-imDC into recipients prolonged liver graft survival, which was sustained for >90 days. IL-12 serum levels decreased, whereas alanine transaminase and total bilirubin slightly increased in rats infused with IL-10-TGF-ß1-imDC compared with the IL-10-imDC and TGF-ß1-imDC groups. Furthermore, a higher percentage of terminal transferase-mediated UTP nick end-labeling-positive cells was observed, and histological analysis of the allografts indicated a rejection activity index of mild acute rejection. Our results suggest infusion of IL-10 and TGF-ß1 cotransfected imDC induces alloantigen-specific T cell hyporesponsiveness, inhibits antigen-specific immunological responses to liver allografts, prolongs liver allograft survival, and enhances the immune tolerance. This approach may provide a promising alternative for enhancing donor-specific tolerance during liver transplantation.
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Células Dendríticas/trasplante , Terapia Genética , Interleucina-10/biosíntesis , Trasplante de Hígado , Hígado/inmunología , Transfección , Factor de Crecimiento Transformador beta1/biosíntesis , Tolerancia al Trasplante , Alanina Transaminasa/sangre , Animales , Apoptosis , Bilirrubina/sangre , Biomarcadores/sangre , Células Cultivadas , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Rechazo de Injerto/genética , Rechazo de Injerto/inmunología , Rechazo de Injerto/metabolismo , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-12/sangre , Isoantígenos/inmunología , Isoantígenos/metabolismo , Hígado/metabolismo , Hígado/patología , Trasplante de Hígado/efectos adversos , Masculino , Modelos Animales , Ratas , Ratas Endogámicas Lew , Linfocitos T/inmunología , Factores de Tiempo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/inmunologíaRESUMEN
In solid tumors, the formidable anti-tumor impact resulting from blocking the "don't eat me" signal, arising from CD47-SIRPα interaction, is constrained, especially compared to its efficacy in hematopoietic malignancies. Activating macrophage anti-tumor activity not only necessitates the inhibition of the "don't eat me" signal, but also the activation of the "eat me" (pre-phagocyte) signal. Intriguingly, the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody (Ab) has been identified to stimulate Fc receptor-mediated active phagocytes in the tumor microenvironment, thereby generating "eat me" signals. This study postulates that concurrently targeting CD47 and CTLA4 could intensify the anti-tumor effects by simultaneously blocking the "don't eat me" signal while triggering the "eat me" signal. The experimental data from this investigation confirm that the combined targeting of CD47 and CTLA4 enhances immunity against solid tumors in LLC cell-transplanted tumor-bearing mice. This effect is achieved by reducing myeloid-derived suppressor cell infiltration while increasing the presence of effector memory CD8+ T cells, NK1.1+ CD8+ T cells, and activated natural killer T cells. Meanwhile, combination therapy also alleviated anemia. Mechanistically, the anti-CD47 Ab is shown to upregulate CTLA4 levels in NSCLC cells by regulating Foxp1. Furthermore, targeting CD47 is demonstrated to promote tumor vascular normalization through the heightened infiltration of CD4+ T cells. These findings suggest that the dual targeting of CD47 and CTLA4 exerts anti-tumor effects by orchestrating the "eat me" and "don't eat me" signals, reshaping the immune microenvironment, and fostering tumor vascular normalization. This combined therapeutic approach emerges as a potent strategy for effectively treating solid tumors.
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OBJECTIVE: Dietary antioxidants are associated with risk of death in cancer patients, and they were used to evaluate the prognosis of cancer patients. Dietary antioxidant index (DAI) can be used to evaluate dietary antioxidant content comprehensively; this study aimed to investigate the effect of preoperative DAI on health-related quality of life in patients with esophageal cell squamous carcinoma (ESCC). METHODS: Data on dietary intakes were collected using a validated food-frequency questionnaire (FFQ). DAI was calculated for all study participants based on FFQ data of each participant. The study involved conducting several follow-up activities with patients diagnosed with ESCC to evaluate their quality of life. The approach employed in the study was to conduct a telephone interview. The EORTC Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30, version 3.0) and the Esophageal Cancer Module (EORTC QLQ-OES18) were used to collect data on the quality of life of the patients; all patients completed the full follow-up. RESULTS: This prospective study was performed on 376 participants who were recruited from Fujian Cancer Hospital and First Hospital of Fujian Medical University. They all were diagnosed with ESCC. The results indicated that the time to deterioration of global health status (p = 0.043), cognitive functioning (p = 0.031), dry mouth (p = 0.019), and speech problems (p = 0.031) significantly delay in the high DAI group. Univariate and multivariate Cox regression analysis showed that global health status (HR = 0.718, 95% CI: 0.532-0.969), cognitive functioning (HR = 0.641, 95% CI: 0.450-0.913), dry mouth (HR = 0.637, 95% CI: 0.445-0.911), and speech problems (HR = 0.651, 95% CI: 0.449-0.945) were improved in the high DAI group. CONCLUSIONS: Prognostic value of preoperative DAI was significant for patients with ESCC who undergo surgical intervention. Its level was positively correlated with the postoperative quality of life of patients, which can delay and improve the occurrence of postoperative physical function and symptom deterioration.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/cirugía , Antioxidantes , Calidad de Vida , Neoplasias Esofágicas/patología , Estudios Prospectivos , Carcinoma de Células Escamosas/epidemiología , Encuestas y CuestionariosRESUMEN
The value of CT-guided puncture with methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses was explored. A total of 113 patients with 146 nodules and masses were treated with methylene blue mixed with autologous blood for preoperative localization and thoracoscopic surgery in the Department of Thoracic Surgery, the First Affiliated Hospital of Fujian Medical University between October 2021 and October 2022. The localization effect, complications, and pathological conditions were observed. The localization success rate was 98.63% (144/146). The localization failed nodules and masses could still be located by looking for needle eyes and reading films. The whole group successfully completed thoracoscopic surgery. The average interval of operation after puncture was 22.16 ± 6.22 h. There was a small amount of suspicious hemothorax after puncture. There was no pneumothorax after puncture in the whole group. There were no hemoptysis, irritating dry cough, and other reactions. The overall complication rate was 2.65%, and no special treatment was given. It is safe and effective to use methylene blue mixed with autologous blood for CT-guided preoperative puncture and localization of small pulmonary nodules and masses.
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BACKGROUND: As a novel alternative to the conventional minimally invasive esophagectomy (MIE) to treat esophageal cancer, single-port laparoscopic retrograde three-step gastric mobilization (SLRM) for esophageal reconstruction during MIE to treat esophageal cancer was attempted in our department. The aim of the present study was to explore the preliminary clinical outcomes and feasibility of this innovative surgery. METHODS: From March 2020 to November 2021, patients undergoing SLRM combined with four-port thoracoscopic McKeown esophagectomy for their esophageal cancers were reviewed. Gastric mobilization with abdominal lymph node dissection was performed through SLRM. The clinical characteristics and short-term outcomes were analyzed retrospectively. RESULTS: A total of 120 patients underwent R0 resection without conversion to open surgery. The mean times needed for the thoracic part, abdominal part, and total operation were 43 ± 6 min, 60 ± 18 min, and 230 ± 20 min, respectively. The numbers of mediastinal and abdominal lymph nodes harvested were 13.2 ± 2.7 and 10.2 ± 2.5, respectively. Postoperative pneumonia was encountered in 10 (8.3%) patients. Anastomotic leakage occurred in 3 (2.5%) cases. Temporary vocal cord paralysis was reported in 20 (16.6%) cases. The mean length of hospital stay was 8.5 ± 4.6 days. CONCLUSIONS: The SLRM is a technically feasible and safe treatment for patients with esophageal cancer. It can be considered an alternative method for patients, especially for the ones with obesity and gastric distension.
RESUMEN
Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previous studies suggest that immature dendritic cells (imDCs) might be involved in the induction of peripheral T cell tolerance. While interleukin-10 (IL-10) functions at different levels of the immune response, transforming growth factor-beta 1 (TGF-beta 1) is considered to be a key factor in immune tolerance. In this study, we investigated the effects of immature DC (imDC) co-transfected with IL-10 and TGF-beta 1 genes (IL-10-TGF-beta 1-imDC) on inducing immune tolerance. Moreover, we compared the effects of IL-10-TGF-beta 1-imDC with IL-10 transfected imDC (IL-10-imDC) and TGF-beta 1-transfected imDC (TGF-beta 1-imDC), respectively. IL-10-TGF-beta 1-imDC resulted in the down-regulation of MHC class II, CD80 and CD86. IL-10-TGF-beta 1-imDC could induce T cell hyporesponsiveness, and was reluctant to proliferate. IL-10-TGF-beta 1-imDC was more effective than IL-10-imDC and TGF-beta 1-imDC, respectively. In summary, co-expression of IL-10 and TGF-beta 1 affected the immunity of imDCs and enhanced their tolerogenicity. It might be a promising therapy for donor-specific tolerance after organ transplantation.
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Células Dendríticas/fisiología , Interleucina-10/biosíntesis , Factor de Crecimiento Transformador beta1/biosíntesis , Animales , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Antígeno B7-2/genética , Antígeno B7-2/metabolismo , Proliferación Celular , Células Cultivadas , Células Dendríticas/metabolismo , Expresión Génica , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/metabolismo , Inmunomodulación/genética , Interleucina-10/genética , Masculino , Ratas Endogámicas Lew , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Linfocitos T/fisiología , Transfección , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
Increasing evidence suggests that plasmacytoma variant translocation 1 (PVT1) plays a vital role in the development of multiple tumors including lung adenocarcinoma (LUAD). Eukaryotic initiation factor 4A-3 (EIF4A3) is considered a key factor in human cancers. However, the role and potential mechanism of PVT1 combined with EIF4A3 in LUAD remain unclear. This study investigated the effects and regulatory mechanisms of PVT1, EIF4A3, and circLMNB2 on the growth, migration, invasion, and epithelial-mesenchymal transition (EMT) of LUAD cells (H1299 and HCC827 cells) The expression level, diagnostic value and prognostic significance of PVT1, EIF4A3, and circLMNB2 were assessed, and enrichment analysis was performed using R package. Rescue experiments and a xenograft model were used to validate the PVT1/EIF4A3/circLMNB2 axis in LUAD. PVT1 and EIF4A3 were upregulated and indicated poor prognosis in LUAD. Knockdown of PVT1 and EIF4A3 suppressed LUAD cell proliferation, migration, invasion, and EMT. Mechanistically, PVT1 was stabilized by EIF4A3. PVT1 could recruit EIF4A3 to promote circLMNB2 expression. Rescue experiments indicated that circLMNB2 overexpression could reverse the reduced behavior caused by PVT1 or EIF4A3 knockdown. Enrichment analysis showed that PVT1/EIF4A3/circLMNB2 may regulate LUAD development by participating in ribosome biogenesis and spliceosome formation. Our findings demonstrate that PVT1/EIF4A3/circLMNB2 enhances the malignant behaviors of LUAD cells, providing a novel perspective for the clinical treatment of LUAD.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Factor 3 de Iniciación Eucariótica/genética , Factor 3 de Iniciación Eucariótica/metabolismo , Factor 4A Eucariótico de Iniciación/genética , Factor 4A Eucariótico de Iniciación/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , ARN Circular , ARN Largo no CodificanteRESUMEN
Background: As a novel alternative to the conventional minimally invasive esophagectomy (MIE), more minimally invasive single-port laparoscopic retrograde 3-step gastric mobilization (SLRM) for esophageal reconstruction during MIE to treat esophageal cancer was attempted by our department. This study explored the preliminary clinical outcomes and feasibility of this innovative surgery. Methods: The data of 120 patients who had undergone SLRM combined with 4-port thoracoscopic McKeown esophagectomy for their esophageal cancers from March 2020 to November 2021 were reviewed. Gastric mobilization with abdominal lymph node dissection was performed via SLRM. The clinical characteristics and short-term outcomes were retrospectively analyzed. The data of operating time, blood loss, harvested lymph nodes, postoperative hospital stay and complications are presented as the mean and standard deviation. Results: A total of 120 patients underwent R0 resection without conversion to open surgery. The mean times for the thoracic procedure, abdominal procedure, and total operation were 43±6, 60±18, and 195±20 min, respectively. The numbers of mediastinal and abdominal lymph nodes harvested were 13.2±2.7, and 10.2±2.5, respectively. Postoperative pneumonia occurred in 10 patients (8.3%). Anastomotic leakage occurred in 3 patients (2.5%). Temporary vocal cord paralysis was reported in 20 patients (16.6%). The mean length of hospital stay was 8.5±4.6 days. Conclusions: SLRM is a technically feasible and safe treatment for patients with esophageal cancer. It can be considered an alternative method for patients, especially those with obesity and gastric distension.