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Accumulation of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau is a histopathological hallmark of Alzheimer's disease (AD) and related tauopathies. Growing evidence demonstrated that tau pathology in AD spreads in a prion-like manner. Previous studies showed that metformin might have a positive effect on cognition. However, the underlying mechanisms are still unknown. Therefore, the present study aimed to investigate the effects of metformin on tau propagation. Brain extracts containing tau aggregates were unilaterally injected into the hippocampus and the overlying cerebral cortex of PS19 mice. Metformin was administrated through drinking water for four months, and we observed tau spreading in the brain of tau-seeded PS19 mice. Metformin inhibited the spreading of tau pathology in the ipsilateral hemisphere, attenuated tau pathology in the contralateral hemisphere, and reduced the hyperphosphorylation of tau at Ser202/Thr205, Thr231, and Ser422 sites in the soluble fraction and Ser202/Thr205, Ser262, Thr396, Thr231, and Ser422 sites in the insoluble fraction of tau-seeded PS19 mice brains. Metformin did not affect tau kinases or phosphatase 2A protein levels but reduced mTORC1 protein levels. Additionally, metformin reduced learning and memory deficits of the tau-seeded PS19 mice. These findings indicate that metformin reduced tau hyperphosphorylation, attenuated tau pathology in tau-seeded PS19 mice, and improved learning and memory deficits. These findings highlight the potential mechanisms underlying the beneficial effects of metformin on cognition, implying that metformin could be a promising drug for the prevention and early treatment of AD.
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Enfermedad de Alzheimer , Metformina , Ratones , Animales , Proteínas tau/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Metformina/metabolismo , Ratones Transgénicos , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Trastornos de la Memoria/metabolismo , Modelos Animales de Enfermedad , FosforilaciónRESUMEN
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the leading cause of cancer-related death worldwide with a poor prognosis. Given that DEPDC1B plays a key role in multiple cancers, the role of this molecule in ESCC was explored to identify potential targets for ESCC patients. METHOD: The expression level of DEPDC1B in ESCC was revealed based on the TCGA database and immunohistochemical experiments on clinical tissues. The correlation between DEPDC1B and survival of ESCC patients was analyzed by Kaplan-Meier method. Small hairpin RNA (shRNA)-mediated silencing of DEPDC1B expression in ESCC cells and performed a series of in vitro and in vivo functional validations. RESULT: DEPDC1B was overexpressed in ESCC. High expression of DEPDC1B was significantly negatively correlated with overall survival in patients with ESCC. Moreover, knockdown of DEPDC1B inhibited ESCC cell proliferation, clone formation, migration, tumor formation and promoted apoptosis. Furthermore, knockdown of DEPDC1B leaded to significant downregulation of GABRD in ESCC cells. Meanwhile, GABRD expression was upregulated in ESCC, and its silencing can inhibit the proliferation and migration of the tumor cells. Interestingly, there was a protein interaction between DEPDC1B and GABRD. Functionally, GABRD knockdown partially reversed the contribution of DEPDC1B to ESCC progression. In addition, GABRD regulated ESCC progression may depend on PI3K/AKT/mTOR signaling pathway. CONCLUSION: DEPDC1B collaborated with GABRD to regulate ESCC progression, and inhibition of this signaling axis may be a potential therapeutic target for ESCC.
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OBJECTIVE: The current work aimed to investigate the expression and potential clinical significance of C-type Lectin domain family 14 (CLEC14A) in hepatocellular carcinoma. METHODS: The relative expressions of CLEC14A in the Hepatocellular Carcinoma (HCC) tissue and adjacent normal tissue of 105 HCC patients were examined using RT-qPCR methods. Furthermore, Receiver Operating Characteristic (ROC) curve was drawn for exploring the diagnostic value of CLEC14A. Next, the expressions of CLEC14A in HCC cell lines and normal liver epithelial cells were compared, and the effects of knockdown of CLEC14A on the growth and apoptosis of HCC cells were examined. RESULTS: The authors found that the expression of CLEC14A was markedly increased in hepatocellular carcinoma tumors in comparison with the adjacent tissue, and the expression level of CLEC14A was positively correlated with the size and differentiation of the tumor. Moreover, results of ROC analysis showed CLEC14A might function as a sensitive diagnostic biomarker for HCC. Furthermore, CLEC14A was up-regulated in HCC cell lines, and transient over-expression of CLEC14A decreased the proliferation and increased the apoptosis of HCC cells in vitro. CONCLUSIONS: Our results suggested that CLEC14A was up-regulated in HCC and might function as a potential diagnostic marker.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptosis , Biomarcadores , Biomarcadores de Tumor , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Moléculas de Adhesión Celular/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Curva ROCRESUMEN
Background: The ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) could improve pathological diagnosis and the selection of treatments for non-small cell lung cancer (NSCLC). Previous studies have shown that deoxyribonucleic acid (DNA) methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers. Methods: We first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus. We then performed whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients. Results: The bioinformatics analysis revealed a NSCLC-specific DNA methylation marker panel, which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on the CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between the CTCs and their primary tumors, and found very high similarities between the CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. However, the CTCs also displayed some characteristics that differed to those of primary tumor tissues, which suggest that CTCs acquire some unique characteristics after migrating from the primary tumor; these characteristics may partly explain the ability of tumor cells to evade immune surveillance. Conclusions: Our findings provide insights into the potential use of CTCs in the pathological classification of NSCLC patients. Our findings also show how CTC primary tumor inheritance and CTC evolution affect metastasis and immune escape.
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Abstract Objective The current work aimed to investigate the expression and potential clinical significance of C-type Lectin domain family 14 (CLEC14A) in hepatocellular carcinoma. Methods The relative expressions of CLEC14A in the Hepatocellular Carcinoma (HCC) tissue and adjacent normal tissue of 105 HCC patients were examined using RT-qPCR methods. Furthermore, Receiver Operating Characteristic (ROC) curve was drawn for exploring the diagnostic value of CLEC14A. Next, the expressions of CLEC14A in HCC cell lines and normal liver epithelial cells were compared, and the effects of knockdown of CLEC14A on the growth and apoptosis of HCC cells were examined. Results The authors found that the expression of CLEC14A was markedly increased in hepatocellular carcinoma tumors in comparison with the adjacent tissue, and the expression level of CLEC14A was positively correlated with the size and differentiation of the tumor. Moreover, results of ROC analysis showed CLEC14A might function as a sensitive diagnostic biomarker for HCC. Furthermore, CLEC14A was up-regulated in HCC cell lines, and transient over-expression of CLEC14A decreased the proliferation and increased the apoptosis of HCC cells in vitro. Conclusions Our results suggested that CLEC14A was up-regulated in HCC and might function as a potential diagnostic marker.
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BACKGROUND: Gastric cancer is a common gastrointestinal cancer and currently has the third-highest mortality rate. Research shows that the natural compound narciclasine has a variety of biological activities. The present study aimed to investigate the effect of narciclasine on gastric cancer cells and its molecular mechanisms and determine whether this compound could be a novel therapy for gastric cancer. METHODS: MTT and clone assays were employed to detect the proliferation of gastric cancer cells. The cell apoptosis was detected by flow cytometry. The formation of autophagosomes and autophagosomal lysosomes was observed by transmission electron microscopy and laser confocal scanning microscopy. Western blotting was used to detect the expression of apoptosis, autophagy and Akt/mTOR pathway-related proteins. RESULTS: In this study, we found that narciclasine could inhibit the proliferation of gastric cancer cells and promote apoptosis in gastric cancer cells. Further experiments showed that narciclasine promoted the levels of autophagy proteins LC3-II, Atg-5 and Beclin-1, reduced the expression of the autophagy transporter p62, and increased autophagic flux. By using the autophagy inhibitors 3-MA and CQ, it was shown that narciclasine could induce autophagy-mediated apoptosis in gastric cancer cells. Finally, we found that narciclasine had no significant effects on the total content of Akt and mTOR in gastric cancer cells, and it involved autophagy in gastric cancer cells by reducing the phosphorylation level of p-Akt and p-mTOR. CONCLUSIONS: Narciclasine can induce autophagy-dependent apoptosis in gastric cancer cells by inhibiting the phosphorylation level of Akt/mTOR and thus reduce the proliferation of gastric cancer cells.
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Alcaloides de Amaryllidaceae/farmacología , Antineoplásicos Fitogénicos/farmacología , Fenantridinas/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Esophageal carcinoma stem cells (ECSCs) are responsible for the initiation and therapy-resistance of esophageal cancer. Nutrient sensor O-GlcNAc transferase (OGT) promoted the growth and metastasis of cancer cells. However, the contributions of OGT to the tumorigenesis of ECSCs remain largely uncover. In the present study, as compared to matched non-stem cancer cells, the expression of OGT was higher in ALDH+ ECSCs. Knock down of OGT by lentivirus system reduced the self-renewal capacities and tumorigenicity of ALDH+ ECSCs. In addition, OGT in exosome derived from ALDH+ ECSCs was taken up by neighboring CD8+ T cells and increased the expression of PD-1 in CD8+ T cells. Down-regulation of OGT increased the apoptosis of ALDH+ ECSCs induced by CD8+ T cells, which could be blocked by overexpression of PD-1 in CD8+ T cells. Together, OGT in exosome from ECSCs protects ECSCs from CD8+ T cells through up-regulation of PD-1.
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Aldehído Deshidrogenasa/genética , Carcinoma/genética , Neoplasias Esofágicas/genética , N-Acetilglucosaminiltransferasas/genética , Receptor de Muerte Celular Programada 1/genética , Apoptosis/genética , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Carcinogénesis/genética , Carcinoma/patología , Línea Celular Tumoral , Neoplasias Esofágicas/patología , Exosomas/enzimología , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Terapia de Inmunosupresión , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patologíaRESUMEN
Background: Although immunotherapy with checkpoint inhibitors is changing the face of lung adenocarcinoma (LUAD) treatments, only limited patients could benefit from it. Therefore, we aimed to develop an immune-relevant-gene-based signature to predict LUAD patients' prognosis and to characterize their tumor microenvironment thus guiding therapeutic strategy. Methods and Materials: Gene expression data of LUAD patients from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were systematically analyzed. We performed Cox regression and random survival forest algorithm to identify immune-relevant genes with potential prognostic value. A risk score formula was then established by integrating these selected genes and patients were classified into high- and low-risk score group. Differentially expressed genes, infiltration level of immune cells, and several immune-associated molecules were further compared across the two groups. Results: Nine hundred and fifty-four LUAD patients were enrolled in this study. After implementing the 2-steps machine learning screening methods, 12 immune-relevant genes were finally selected into the risk-score formula and the patients in high-risk group had significantly worse overall survival (HR = 10.6, 95%CI = 3.21-34.95, P < 0.001). We also found the distinct immune infiltration patterns in the two groups that several immune cells like cytotoxic cells and immune checkpoint molecules were significantly enriched and upregulated in patients from the high-risk group. These findings were further validated in two independent LUAD cohorts. Conclusion: Our risk score formula could serve as a powerful and accurate tool for predicting survival of LUAD patients and may facilitate clinicians to choose the optimal therapeutic regimen more precisely.
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Uniportal video-assisted thoracic surgery (VATS) was growing popular since its first introduction. Based on the conventional uniportal VATS, we modified the technique and introduced transaxillary uniportal VATS lobectomy in this case report. In March 2017, transaxillary uniportal VATS was firstly attempted on a patient suffering from right upper lobe lesion at the Department of Thoracic Surgery, Zhongshan Hospital, Fudan University. A 4-cm single incision was made at the fossa axillaris paralleled to the skin folds, to which a soft wound protector was applied to reach the third intercostal space along the anterior axillary line. The right upper lobectomy was performed through the transaxillary incision. The surgery was accomplished without conversion to thoracotomy or application of extra incision. The truncus anterior artery, the upper lobe bronchus and upper pulmonary vein was mobilized and dissected in order. The target lobe was removed through the fossa axillaris incision. The operation duration was 110 minutes with limited blood loss. The patient was discharged 3 days post-operatively. Transaxillary uniportal VATS lobectomy is safe and feasible, and the procedure showed cosmetic advantages. Further studies based on larger population are required to determine these findings.
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Introduction: Esophageal cancer is one of the most common malignant tumors in the world. Eukaryotic translation initiation factors 3e (eIF3e) makes a notable difference in the initiation of protein synthesis and tumor progression. However, the role of eIF3e in ESCC has not been revealed yet. This study aims to investigate the bio-functional and prognostic role of eIF3e in human ESCC tissues and cells. Methods: Immunohistochemical staining and Western blot were performed to detect the eIF3e expression in ESCC patients' tissues. The Kaplan-Meier product limit method and Cox regression were conducted to analyze the association between eIF3e expression, together with other related clinical/pathological features, and patients' prognosis. In the analysis of bio-functional role of eIF3e, CCK-8 and Transwell assay were performed to compare the proliferative and migrative ability after knockdown of eIF3e. Results: Up-regulation of eIF3e were demonstrated in ESCC tissues compared with the corresponding para-cancerous tissues. Overexpression of eIF3e was associated with deep tumor depth, lymph nodes metastasis, and advanced TNM stage. Importantly, the patients with high eIF3e expression suffered shorter overall and disease-free survival. Lymph node metastasis and histological grade served as independent prognostic predictors in patients' prognosis. Knockdown of eIF3e could inhibit cell proliferation and migration, in vitro. Conclusions: The eIF3e expression, or combined with other members of eIF3 complex, might predict poor prognosis of ESCC and serve as a potential breakthrough in the multimodality therapy of ESCC.
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BACKGROUND: Three-dimensional (3D) simulation of pulmonary vessels and the space between the lesion and adjacent tissues may improve the safety and accuracy of video-assisted thoracoscopic surgery (VATS) for lung. The aim of this study was to evaluate the effect of 3D simulation on the outcome of VATS segmentectomy for ground glass opacity (GGO) in lung. METHODS: We retrospectively analyzed 68 cases of small (≤2 cm) GGO, which were diagnosed as cT1aN0M0 lung cancer, from May 1, 2016 to February 28, 2017 in our institute. All the patients underwent VATS segmentectomy. The patients were divided into "3D" group, 3D preoperative reconstruction simulation in 36 patients and "non-3D" group, 32 patients with only computed tomography (CT). Operation plans were firstly made by CT in all patients, then by 3D simulation only in 3D group. The clinical outcomes, including operation time, blood loss, resection margin distance, length of postoperative stay and postoperative complications were compared between the two groups. RESULTS: There were 21 male and 47 female analyzed, aging from 34 to 72 years (median 57). In 3D group, pathological result showed 8 cases of adenocarcinoma, 23 cases of microinvasive adenocarcinoma (MIA), 5 cases of adenocarcinoma in situ (AIS). In non-3D group, 18 cases of MIA, 9 cases of adenocarcinoma and 5 cases of AIS were diagnosed pathologically. The blood loss, postoperative hospital stay and the incidence of the postoperative complications were similar in both of the groups. There was no 30-day postoperative mortality in either group. The median operation time for the 3D group (111 minute) was shorter than non-3D group (139 minute) (P=0.03). Seven cases (19%) in 3D group changed the original operation plan according to the simulation result with the consideration of adequate resection margin distance. All cases in 3D group had adequate resection margin distance. Four cases (13%) in non-3D group got inadequate resection margin distance, and more lung tissues than the original plan were then resected in these patients (P=0.04). CONCLUSIONS: 3D preoperative simulation may be more precise in operation plan than CT scan and can significantly shorten the operation time in VATS segmentectomy for GGO in lung.
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A ground-glass opacity (GGO) lesion was discovered in a 64-year-old female 1 year ago. One month before administration, a follow-up CT showed the lesion in the apical segment of left upper lobe had increased from 8 to 11 mm in diameter. The lesion was diagnosed to be cT1aN0M0 non-small cell lung cancer (NSCLC) and a 3-port video-assisted thoracic surgery (VATS) anatomic segmentectomy was performed. Intraoperative frozen sections revealed a microinvasive adenocarcinoma. Systematic lymph node dissection was then carried out. The final pathological result showed a pT1aN0M0 (Ia) adenocarcinoma.
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OBJECTIVES: Total thymectomy should be performed on thymoma patients with myasthenia gravis. The aim of the present study was to investigate the risk factors of postoperative myasthenic crisis (POMC) occurrence in these patients. METHODS: The clinical records of 127 thymoma patients with myasthenia gravis (68 men, 59 women; median age, 50 years) who underwent total thymectomy at our institution from 2005 to 2014 were retrospectively reviewed. The following factors were analysed in relation to POMC: gender, age, duration of symptoms, bulbar symptoms, smoking history, history of myasthenic crisis, comorbidities, perioperative pyridostigmine and prednisolone therapy, spirometric and blood gas parameters, Osserman stage, operation approach, major complications, World Health Organization (WHO) histologic classification, Masaoka stage and use of immunoglobulins or plasmapheresis. RESULTS: Thirteen patients (10%) experienced POMC and required intubation. All patients were weaned after 2-28 days (median 9 days) and were discharged. Univariate analysis revealed a correlation between POMC and Osserman-stage IIA-IV [odds ratio (OR) = 4.928, 95% confidence interval (CI) = 1.286-18.882, P = 0.01], bulbar symptoms (OR = 3.828, 95% CI = 1.112-13.176, P = 0.04), and forced expiratory volume in one second <70% pred forced expiratory volume in one second (OR = 4.856, 95% CI = 1.380-17.081, P = 0.02). In addition, more frequent POMC occurred in WHO type B2-B3 than in type A-B1 thymomas (OR = 8.118, 95% CI = 1.020-64.590, P = 0.03). Multivariate logistic regression analysis showed that WHO histologic classification B2-B3 (OR = 10.041, 95% CI = 1.228-82.090, P = 0.03) and Osserman-stage IIA-IV (OR = 5.953, 95% CI = 1.506-23.538, P = 0.01) independently predicted POMC. CONCLUSIONS: Osserman stage (IIA-IV) and WHO type B2-B3 thymomas are independent predictors of POMC in thymoma patients with myasthenia gravis who have undergone total thymectomy. Thus, adequate perioperative care should be provided to these patients.
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Miastenia Gravis/epidemiología , Complicaciones Posoperatorias/epidemiología , Medición de Riesgo , Timectomía/efectos adversos , Timoma/cirugía , Neoplasias del Timo/cirugía , Adolescente , Adulto , Anciano , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Miastenia Gravis/etiología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors. Eukaryotic translation initiation factors 3B (EIF3B) is considered to influence tumor proliferation, invasion, apoptosis and cell cycle, which act together to promote the progression of tumors. However, the role of EIF3B in ESCC is unknown. This study aims to explore the clinical and biological role of EIF3B in ESCC. RESULTS: EIF3B expressions were up-regulated in both ESCC tissues and cell lines. Overexpression of EIF3B was associated with tumor depth, lymph node metastasis and advanced TNM stage. Importantly, patients with high EIF3B expression suffered shorter overall and disease-free survival. Knockdown of EIF3B could inhibit cell proliferation and invasion, promote cell apoptosis, and interfere the cell cycle in vitro. EIF3B-knockdown cells could form smaller subcutaneous tumors in vivo. Finally, we demonstrated EIF3B could activate ß-catenin signaling pathway. METHODS: Immunohistochemical staining and Western blot were performed to detect the EIF3B expression in ESCC patient tissues and cell lines. The association between EIF3B expression and patients' prognosis was analyzed by Kaplan-Meier and Cox regression. Then, CCK-8, colony-formation, Transwell and wound-healing assay were performed to compare the bio-functional change after knockdown of EIF3B. Flow cytometry was applied to analyze the change of cell apoptosis and cycle induced by EIF3B knockdown. Tumor xenograft assay was done to verify the in-vitro results. CONCLUSIONS: EIF3B might serve as a novel marker for predicting prognosis of ESCC patients and as a potential therapeutic target, individually or together with other subunits of EIF3 complex.
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Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Factor 3 de Iniciación Eucariótica/metabolismo , beta Catenina/metabolismo , Apoptosis , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/cirugía , Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Femenino , Estudios de Seguimiento , Técnicas de Silenciamiento del Gen , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Regulación hacia ArribaRESUMEN
PURPOSE: The management of chronic empyema with persistent bronchopleural fistula (BPF) is a major challenge for surgeons. We report our experience of performing pedicle muscle flap transposition for chronic empyema with BPF in a clinical center in China. METHODS: The subjects of this study were 13 patients with postoperative chronic empyema and persistent BPF. The surgical procedure performed was chosen according to the degree of infection in the empyema cavity. Patients with mild contamination underwent one-stage cavity decortication with flap transposition, whereas patients with severe infection underwent two-stage surgery including open-window thoracostomy and pedicle muscle flap transposition. RESULTS: Five patients underwent one-stage surgery, followed by an uneventful postoperative course in all except one. The other eight patients underwent two-stage surgery. The fistulas closed spontaneously during the course of dressings and six of these eight patients underwent second-stage surgery uneventfully. A bronchopleurocutaneous sinus developed in the wounds of the other two patients. CONCLUSIONS: Pedicle muscle flap transposition is a viable option for chronic empyema with BPF; however, surgical procedures should be selected according to the degree of contamination. For two-stage surgery, obliteration of the cavity should be considered, preferably after closure of the fistula.
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Fístula Bronquial/cirugía , Empiema/cirugía , Fístula/cirugía , Enfermedades Pleurales/cirugía , Complicaciones Posoperatorias/cirugía , Colgajos Quirúrgicos , Adulto , China , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Torácicos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To investigate lymph node metastasis especially the intrapulmonary node in clinical IA peripheral lung cancer patients to evaluate the indications for lung segmentectomy in lymph node level. MATERIALS AND METHODS: Patients (n=292) with clinical stage IA peripheral lung cancer received radical lobectomy at our department between October 2013 and July 2014 were enrolled in our study. Lymph nodes were obtained during routine surgical procedures while segmental lymph nodes were dissected from the resected lobe for pathological examination. New classification for pulmonary adenocarcinoma with each histologic component was also analyzed. RESULTS: The percentage of patients found to have no lymph node metastasis was 90.4% (264/292). Tumor size on computed tomography and tumor consistency were independent predictors for lymph node metastasis. Tumor with a dominant ground-glass opacity (GGO) component was a good predictor for lymph node metastasis (p<0.001). Metastasis was more common in larger tumors (p<0.001), but there was non-tumor bearing segment metastasis even in tumor less than 1cm. Patients with micropapillary or solid component were correlated with lymph node metastasis (p=0.001 and p=0.009, respectively). CONCLUSIONS: The rate of metastasis to the lymph nodes is very low in clinical stage IA peripheral lung cancer patients. Patients with a dominant GGO component on CT might be the suitable candidates for lung segmentectomy because of almost no lymph node metastasis. Careful selection should be made for the patients with tumor size ≤2 cm who had metastasized nodes in non-tumor bearing segment when considering segmentectomy. If the resected tumor had micropapillary or solid component, the lobectomy might be considered.
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Neoplasias Pulmonares/patología , Ganglios Linfáticos/patología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adenocarcinoma del Pulmón , Carcinoma de Células Escamosas/parasitología , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/cirugía , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Mastectomía Segmentaria/métodos , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Mioepitelioma/patología , Mioepitelioma/cirugía , Estadificación de Neoplasias , Neumonectomía/métodos , Pronóstico , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: Esophageal squamous cell carcinoma is one of the most frequent malignant tumors. Cancer stem cells are considered to be responsible for tumor growth, metastasis, and recurrence. Cluster of differentiation 133 (CD133) and C-X-C chemokine receptor type 4 (CXCR4) are frequently applied markers for the identification and isolation of cancer stem cells. However, few studies have investigated the coexpression of CD133 and CXCR4 in esophageal squamous cell carcinoma. This study aims to explore the clinical and biological role of stem-like CD133(+)CXCR4(+) cells in esophageal squamous cell carcinoma. METHODS: Immunohistochemical staining was performed to detect the expression of CD133 and CXCR4 in esophageal squamous cell carcinoma tissues of patients. Flow cytometry and fluorescence-activated cell sorting were applied to analyze and isolate each subgroup in esophageal squamous cell carcinoma cell line TE-1. The characteristic differences between each subgroup were assayed in vitro. The association between CD133/CXCR4 expression and patients' prognosis was analyzed by Kaplan-Meier and Cox regression. RESULTS: Among 154 patient tissues, concomitant high CD133-CXCR4 expression accounts for 20.78% (32/154). In vitro, CXCR4(+) cells (CD133(+)CXCR4(+) and CD133(-)CXCR4(+)) showed high invasive potential and CD133(+)CXCR4(+) cells showed high proliferative capacity. Clinically, patients with concomitant high CD133-CXCR4 expression had decreased disease-free survival and overall survival (P < .01). CONCLUSIONS: Esophageal squamous cell carcinoma cells coexpressing CD133 and CXCR4 possess the characteristics of cancer stem cells. The concomitant high CD133-CXCR4 expression might be a novel marker for predicting the poor prognosis of patients with esophageal squamous cell carcinoma, and CD133 and CXCR4 may serve as potential therapeutic targets.
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Antígenos CD/análisis , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/inmunología , Neoplasias Esofágicas/inmunología , Glicoproteínas/análisis , Células Madre Neoplásicas/inmunología , Péptidos/análisis , Receptores CXCR4/análisis , Antígeno AC133 , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Separación Celular/métodos , Supervivencia sin Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago , Femenino , Citometría de Flujo , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Células Madre Neoplásicas/patología , Modelos de Riesgos ProporcionalesRESUMEN
In non-small cell lung cancer (NSCLC), both USP7 expression and p53 gene status were reported to be an indicator of poor prognosis in adenocarcinoma patients; however, its roles and mechanisms in lung squamous cell carcinoma and large cell carcinoma need to be clarified. The USP7 expression was examined in NSCLC tumors (excluding adenocarcinoma), their corresponding non-tumorous tissues, and NSCLC cells. Then, the prognostic role of USP7 was analyzed in 110 NSCLC samples (excluding the adenocarcinoma). Finally, the roles and mechanisms of USP7 in the proliferation, metastasis, and invasion of a NSCLC cell were assessed using a specific vshRNA. The USP7 expression was higher in NSCLC tissues compared to non-tumorous samples, accordingly, the high level of USP7 was detected in NSCLC cell lines compared with HBE cell. After the USP7 downregulation, the H460 cells exhibited decreased metastasis/invasion in vitro and in vivo. The preliminary mechanism study indicated overexpression of USP7 might regulate the p53-MDM2 pathway by inducing the MDM2 de-ubiquitination and subsequent stabilization, which resulted in the upregulation of the Bad phosphorylation. Additionally, we also found that USP7 might induce cell epithelial-mesenchymal transition to enhance the cell invasive ability. Clinically, USP7 overexpression significantly correlated with malignant phenotype. Furthermore, the 5-year overall survival in patients with USP7(low) was higher than that of USP7(high). Multivariate analysis showed USP7 overexpression was an independent prognostic marker for these cancers. USP7 overexpression may regulate the survival and invasive properties of squamous cell carcinoma and large cell carcinoma cells, and may serve as a molecular target.
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Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Pulmonares/metabolismo , Ubiquitina Tiolesterasa/biosíntesis , Animales , Carcinoma de Células Grandes/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Regulación hacia Abajo , Transición Epitelial-Mesenquimal/genética , Femenino , Humanos , Neoplasias Pulmonares/genética , Metástasis Linfática/diagnóstico , Metástasis Linfática/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteína p53 Supresora de Tumor/genética , Ubiquitina Tiolesterasa/genética , Peptidasa Específica de Ubiquitina 7 , Regulación hacia ArribaRESUMEN
PURPOSE: We investigated the expression of epithelial Ca2+ channel transient receptor potential vanilloid (TRPV) 5 and 6 in non-small-cell lung cancer (NSCLC) and assessed their prognostic role in patients after surgical resection. MATERIALS AND METHODS: From January 2008 to January 2009, 145 patients who had undergone surgical resection of NSCLCs were enrolled in the study. Patient clinical characteristics were retrospectively reviewed. Fresh tumor samples as well as peritumor tissues were analyzed for TRPV5/6 expression using immune-histochemistry (IHC) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Patients were grouped based on their TRPV5 and TRPV6 levels in the tumor tissues, followed up after surgery, and statistically analyzed to examine the prognostic roles of TRPV5 and TRPV6 on patients' survival after surgical resection of NSCLCs. RESULTS: Using IHC, among the 145 patients who had undergone surgical resection of NSCLCs, strong protein expression (grade ≥ 2) of TRPV5 and TRPV6 was observed in a lower percentage of primary tumor tissues than in non-tumor tissues of same patients. Similar findings were obtained with the RT-PCR test for mRNA levels. Decreased overall mRNA levels of TRPV5 and TRPV6 were associated with a worse overall survival rate (p=0.004 and p=0.003 respectively) and shorter recurrence-free survival (p?0.001 and p?0.001 respectively). The combining effect of TRPV5 and TRPV6 on survival was further investigated using multivariate analysis. The results showed that a combination of low expression of TRPV5 and TRPV6 could be an independent predictor of poor recurrence-free survival (p=0.002). CONCLUSIONS: Decreased expression of TRPV5/6 in tumor tissues was observed in NSCLC patients and was associated with shorter median survival time after surgical resection. Combined expression of TRPV5 and TRPV6 in tumor tissues demonstrated promising prognostic value in NSCLC patients.