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PURPOSE: Development and validation of a radiomics model for predicting occult locally advanced esophageal squamous cell carcinoma (LA-ESCC) on computed tomography (CT) radiomic features before implementation of treatment. METHODS: The study retrospectively collected 574 patients with esophageal squamous cell carcinoma (ESCC) from two medical centers, which were divided into three cohorts for training, internal and external validation. After delineating volume of interest (VOI), radiomics features were extracted and subjected to feature selection using three robust methods. Subsequently, 10 machine learning models were constructed, among which the optimal model was utilized to establish a radiomics signature. Furthermore, a predictive nomogram incorporating both clinical and radiomics signatures was developed. The performance of these models was evaluated through receiver operating characteristic curves, calibration curves, decision curve analysis as well as measures including accuracy, sensitivity, and specificity. RESULTS: A total of 19 radiomics features were selected. The multilayer perceptron (MLP), which was found to be optimal, achieved an AUC of 0.919, 0.864 and 0.882 in the training, internal and external validation cohorts, respectively. Similarly, MLP showed good accuracy in distinguish occult LA-ESCC in subgroup of cT1-2N0M0 diagnosed by clinicians with 0.803 and 0.789 in two validation cohorts respectively. By incorporating the radiomics signature with clinical signature, a predictive nomogram demonstrated superior prediction performance with an AUC of 0.877 and accuracy of 0.85 in external validation cohort. CONCLUSION: The radiomics and machine learning model can offers improved accuracy in prediction of occult LA-ESCC, providing valuable assistance to clinicians when choosing treatment plans.
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Purpose: The need for adjuvant therapy (AT) following neoadjuvant chemoimmunotherapy (nICT) and surgery in esophageal squamous cell cancer (ESCC) remains uncertain. This study aims to investigate whether AT offers additional benefits in terms of recurrence-free survival (RFS) for ESCC patients after nICT and surgery. Methods: Retrospective analysis was conducted between January 2019 and December 2022 from three centers. Eligible patients were divided into two groups: the AT group and the non-AT group. Survival analyses comparing different modalities of AT (including adjuvant chemotherapy and adjuvant chemoimmunotherapy) with non-AT were performed. The primary endpoint was RFS. Propensity score matching(PSM) was used to mitigate inter-group patient heterogeneity. Kaplan-Meier survival curves and Cox regression analysis were employed for recurrence-free survival analysis. Results: A total of 155 nICT patients were included, with 26 patients experiencing recurrence. According to Cox analysis, receipt of adjuvant therapy emerged as an independent risk factor(HR:2.621, 95%CI:[1.089,6.310], P=0.032), and there was statistically significant difference in the Kaplan-Meier survival curves between non-AT and receipt of AT in matched pairs (p=0.026). Stratified analysis revealed AT bring no survival benefit to patients with pathological complete response(p= 0.149) and residual tumor cell(p=0.062). Subgroup analysis showed no significant difference in recurrence-free survival between non-AT and adjuvant chemoimmunotherapy patients(P=0.108). However, patients receiving adjuvant chemotherapy exhibited poorer recurrence survival compared to non-AT patients (p= 0.016). Conclusion: In terms of recurrence-free survival for ESCC patients after nICT and surgery, the necessity of adjuvant therapy especially the adjuvant chemotherapy, can be mitigated.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/terapia , Terapia Neoadyuvante , Neoplasias Esofágicas/patología , Estudios Retrospectivos , Puntaje de Propensión , Supervivencia sin EnfermedadRESUMEN
BACKGROUND: The effects of minimally invasive total mesoesophageal excision (MITME) on the long-term prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remain unknown. The objective of this study was to compare the static and dynamic failure patterns of MITME and minimally invasive esophagectomy (MIE) for locally advanced ESCC. METHODS: We use propensity score matching (PSM) method to analyze the postoperative failure patterns of the two groups. Cumulative event curves were analyzed for cumulative incidence of failure between different groups, and independent prognostic factors were assessed using time-dependent multivariate analyses. The risk of dynamic failure calculated at 12-month intervals was compared between the two groups using the lifetime table. RESULTS: A total of 366 ESCC patients were studied by 1:1 PSM for T stage and TNM stage (MITME group, n = 183; MIE group, n = 183). In the matched cohort, there was significant differences between the MITME and MIE groups in the failure pattern of regional lymph node recurrence (0.5 vs 3.8%, P = 0.032) and non-tumor death (10.9 vs 31.7%, P < 0.001). The cumulative event curve found that the 5-year cumulative failure rate was lower in the MITME group than in the MIE group (3.3 vs 17.1%, P = 0.026) after 5 years of survival. In addition, multivariate Cox regression analysis showed that MIE was an independent poor prognostic factor for a high cumulative failure rate in locally advanced ESCC patients at 5 years after surgery (HR:4.110; 95% CI 1.047-16.135; P = 0.043). The dynamic risk curve showed that the MITME group had a lower risk of failure within 5 years after surgery than the MIE group. CONCLUSION: Considering that MITME can significantly improve the postoperative failure pattern and the benefit lasts for at least 5 years, it is feasible to use MITME as a treatment for locally advanced ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/cirugía , Neoplasias Esofágicas/patología , Estudios de Seguimiento , Estudios de Cohortes , Esofagectomía/métodos , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodosRESUMEN
BACKGROUND: Primary focal hyperhidrosis (PFH) is an autonomic neurological disease in which exocrine glands are oversecreted due to autonomic dysfunction of the sympathetic nervous system. Chrna1 promotes the pathogenesis of PFH. We aimed to check if downregulating of Chrna1 by cisatracurium could alleviate the symptoms of PFH. METHODS: The effect of cisatracurium in a hyperhidrosis mice model induced by pilocarpine hydrochloride was monitored for sweat gland secretion, and ultrastructural sweat secretory granules in sweat glands were analyzed. Meanwhile, markers of hyperhidrosis were checked, and release of Bdnf and Nrg1 from sympathetic ganglia axon was tested. Furthermore, the mechanism of cisatracurium function was evaluated in vitro using HEK293 expressing Chrna1. Finally, the effect of cisatracurium was determined in the hyperhidrosis mice model with overexpression or downregulation of Chrna1. RESULTS: In hyperhidrosis mice, pretreatment with cisatracurium effectively inhibited sweat secretion, along with fewer particle secretion in sweat glands. The molecular markers of hyperhidrosis (Aqp5 and Cacna1c) were inhibited by cisatracurium, acetylcholine (Ach) level in serum was found decreased. Neurotrophic factors (Bdnf and Nrg1) secreted by sympathetic axon activation were also inhibited. At last, it was confirmed that cisatracurium could not alter the gene or protein expression level of Chrna1, but could block the ion channel. Overexpression of Chrna1 abolished the effect of cisatracurium on hyperhidrosis, while cisatracurium could not function more in siChrna1-treated mice. CONCLUSION: Our results suggested that pretreatment of cisatracurium could alleviate hyperhidrosis in mice, probably through blocking the ion channel function of Chrna1.
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Hiperhidrosis , Antagonistas Nicotínicos , Receptores Nicotínicos , Animales , Factor Neurotrófico Derivado del Encéfalo , Células HEK293 , Humanos , Hiperhidrosis/tratamiento farmacológico , Hiperhidrosis/patología , Ratones , Antagonistas Nicotínicos/farmacología , Pilocarpina , Receptores Nicotínicos/metabolismo , Glándulas Sudoríparas/metabolismo , Glándulas Sudoríparas/patologíaRESUMEN
The aim of the study was to elucidate the involvement of cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) in the pathogenesis of primary focal hyperhidrosis (PFH). The hyperhidrosis mouse model was constructed using pilocarpine injection. The expression levels of CHRNA1 in sweat gland tissues of PFH patients and hyperhidrosis mice were compared using Western blots and quantitative real-time PCR (qRT-PCR) analyses. Sweat secretion in hyperhidrosis mice treated with small-interfering RNA (siRNA) targeting CHRNA1 (si-CHRNA1) or non-specific siRNA were compared. Sweat secretory granules in the sweat gland cells of hyperhidrosis mice were examined using transmission electron microscopy. The serum level of acetylcholine was measured using enzyme-linked immunosorbent assay, while markers associated with PFH, including Aquaporin 5 (AQP5) and Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C), were assessed using immunohistochemical assay and Western blots. Brain-derived neurotrophic factor (BDNF) and Neuregulin 1 (NRG-1) in sympathetic ganglia axons of hyperhidrosis mice were quantified using Western blots. CHRNA1 up-regulation is a characteristic of the sweat glands of PFH patients and Hyperhidrosis mice. Silencing CHRNA1 decreased sweat secretion and the number of sweat secretory granules of hyperhidrosis mice. Serum acetylcholine, as well as AQP5 and CACNA1C expression in the sweat glands, was reduced by siCHRNA1. BDNF1 and NRG-1 levels in the sympathetic ganglia axons were also attenuated by siCHRNA1 treatment. CHRNA1 up-regulation is a potential biomarker of PFH and downregulating CHRNA1 could alleviate the symptoms of PFH through inactivating the sympathetic system.
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Hiperhidrosis/metabolismo , Receptores Nicotínicos/metabolismo , Glándulas Sudoríparas/metabolismo , Acetilcolina/sangre , Animales , Acuaporina 5/genética , Acuaporina 5/metabolismo , Canales de Calcio Tipo L/genética , Canales de Calcio Tipo L/metabolismo , Humanos , Hiperhidrosis/genética , Ratones , Ratones Endogámicos BALB C , Receptores Nicotínicos/genéticaRESUMEN
The pathogenesis of primary focal hyperhidrosis (PFH) is still not clear. PFH is thought to be a genetic disease. Whether activin A receptor type 1 (ACVR1) is involved in the pathogenesis of PFH is unknown. In this study, the expression of ACVR1 in sweat glands of patients with PAH was detected by western blot and immunofluorescence. The primary sweat gland cells obtained from primary axillary hyperhidrosis (PAH) patients were transfected with acvr1 vector. Cell proliferation, apoptosis and cell cycling of gland cells were measured after transfection with acvr1 vector. The mRNA and protein expression of aquaporin 5 (AQP5) and Na:K:2Cl Cotransporter 1 (NKCC1/SLC12A2) were detected. Our data showed that ACVR1 expression in axillary sweat gland tissue of PAH patients was significantly higher than that of normal control group. The function of ACVR1 was further investigated in the gland cells obtained from PAH patients. Compared with NC group, ACVR1 overexpression significantly promoted the proliferation of sweat gland cells and inhibited the apoptosis of sweat gland cells. Meanwhile, ACVR1 overexpression significantly reduced the percentage of cells in G0/G1 and G2/M phases, and increased the percentage of cells in S phase. In addition, ACVR1 overexpression significantly promoted the expression of AQP5 and NKCC1 at both mRNA and protein levels. Together, ACVR1 expression is related to PFH and ACVR1 overexpression can promote the proliferation of sweat gland cells and inhibit apoptosis by promoting the expression of AQP5 and NKCC1.
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Receptores de Activinas Tipo I/metabolismo , Hiperhidrosis/metabolismo , Hiperhidrosis/patología , Apoptosis , Acuaporina 5/genética , Acuaporina 5/metabolismo , Proliferación Celular , Regulación de la Expresión Génica , Humanos , Hiperhidrosis/genética , Miembro 2 de la Familia de Transportadores de Soluto 12/genética , Miembro 2 de la Familia de Transportadores de Soluto 12/metabolismo , Glándulas Sudoríparas/metabolismo , Glándulas Sudoríparas/patologíaRESUMEN
BACKGROUND: Transareolar single-port endoscopic thoracic sympathectomy (ETS) with a flexible endoscope has rarely been reported. This study assessed the performance of this novel minimally invasive technique for primary palmar hyperhidrosis (PPH). METHODS: From January 2019 to September 2019, 118 males with severe PPH requiring single-port and bilateral ETS were randomly allocated to undergo transareolar ETS using a flexible endoscope (group A, n=58) or transaxillary ETS using a 5 mm thoracoscope (group B, n=60). RESULTS: Both groups had similar patient characteristics. All procedures were performed successfully, with no mortality or conversion to open surgery. All patients had dry and warm palms immediately after surgery. Compared with group B, group A had a significantly shorter median incision length [5.1 (5.0-5.2) vs. 10.9 (10.8-11.9) mm; P<0.001], and significantly lower median postoperative pain score [1 (1.0-2.0) vs. 3 (3.0-4.0); P<0.001]. There were no differences between the two groups in operative time, palmar temperature increase, and transient postoperative sweating. After complete follow-up, group A had a significantly higher median cosmetic score than group B [4.0 (3.0-4.0) vs. 3.0 (3.0-3.0); P<0.001]. There were no differences between the two groups regarding symptom resolution, compensatory hyperhidrosis, and satisfaction score. No patient reported residual pain or symptom recurrence. CONCLUSIONS: Transareolar single-port ETS with a flexible endoscope is safe, effective, and minimally invasive with a small incision, minimal pain, and excellent cosmetic results. This novel procedure is suitable for routine treatment of PPH in males.
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Controversy about the adequate extent of lymph node (LN) dissection persists in surgery for thoracic esophageal squamous cell carcinoma (ESCC). The present study estimates the feasibility and strategy of common hepatic artery LN dissection during ESCC surgery.The clinical data of 482 patients with ESCC, who underwent thoracolaparoscopic esophagectomy at Fujian Medical University Union Hospital, were retrospectively selected. Among the 482 ESCC patients, 224 patients underwent thoracolaparoscopic esophagectomy with routine common hepatic artery LN dissection (cohort 1), while 258 patients underwent the same procedure without common hepatic artery LN dissection (cohort 2). The proposed operation method was introduced to safely dissect the common hepatic artery LN. Both univariate and multivariate analyses were performed to analyze the clinicopathological factors correlated to the common hepatic artery LN metastasis.The main postoperative complications were pneumonia, anastomotic leakage, vocal cord palsy and cardiovascular disease. There was no significant difference in the incidence of major postoperative complications between the 2 cohorts (Pâ>.05), and the incidence was similar in a number of reports. The metastatic rate of common hepatic artery LNs was 4.91%, which was relatively lower. Based on the logistic regression analysis of 5 factors, tumor location and T classification were risk factors for common hepatic artery LN metastasis (Pâ<.05).Routine common hepatic artery LN dissection is safe and feasible during a thoracolaparoscopic esophagectomy for ESCC. Although the metastatic rate is lower, common hepatic artery LN dissection should be performed for lower thoracic ESCCs, especially for tumors that invade the outer membrane.
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Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/cirugía , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Neoplasias Torácicas/cirugía , Toracoscopía/métodos , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Estudios de Factibilidad , Femenino , Arteria Hepática/cirugía , Humanos , Incidencia , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Neoplasias Torácicas/patología , Resultado del TratamientoRESUMEN
Numerous esophageal squamous cell carcinoma (ESCC) patients exhibit tumor recurrence following radical resection. Invasion and metastasis are key factors in poor prognosis following esophagectomy. In the present study, twodimensional gel electrophoresis (2-DE) and matrixassisted laser desorption/ionization time-of-flight mass spectrometry were used to define patterns of protein expression in ESCC tissues at different pathological stages. The expression levels of identified proteins were determined by immunohistochemistry and western blotting. A total of fifteen protein spots with >2-fold differences were observed when comparing results of 2-DE for stage III and stage I ESCC tissue sample. A total of 12 proteins were identified by mass spectrometry analysis and database searches. The results of immunohistochemistry and western blotting demonstrated expression levels of tropomyosin 3 (TPM3) were higher in stage III ESCC tissue compared with stage I (P<0.05). The findings of the present study identified twelve proteins, which are closely associated with ESCC invasion and metastasis, apoptosis and cell signal transduction. Furthermore, the overexpression of TPM3 may be important in ESCC invasion and metastasis.
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Biomarcadores de Tumor , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Proteómica , Tropomiosina/metabolismo , Anciano , Carcinoma de Células Escamosas/patología , Electroforesis en Gel Bidimensional , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Proteómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
BACKGROUND: Complete video-assisted thoracoscopic surgery (c-VATS) for left upper lobectomy is difficult due to the branching pattern of the left pulmonary artery. OBJECTIVE: Our purpose was to report outcomes of a modified technique of c-VATS left upper lobectomy. METHODS: We retrospectively compared the outcomes of 83 patients with stage I/II non-small-cell lung cancer (NSCLC) who received left upper lobectomy between 2008 and 2011; 32 underwent conventional c-VATS and 50 received modified c-VATS. In the modified procedure, the order in which hilum of lung was treated was from the lingular segmental artery to the superior pulmonary vein to the bronchus, and then finally the pulmonary artery. RESULTS: The mean patient age was 63.6 ± 8.4 years, and no differences were observed in age, gender, and largest tumor diameter between the two groups. No conversion occurred in either group. The surgical time for modified c-VATS was significantly shorter than that for conventional c-VATS (210 vs. 270 min, p < 0.001). Drainage time after surgery and length of hospitalization for the modified c-VATS group were significantly less than those for the conventional group (drainage 3 vs. 4 days, respectively, p = 0.041; length of hospitalization 7 versus 12 days, respectively; p < 0.001). Surgical margins were clear in all cases. Four (8.0 %) complications occurred in the modified procedure group compared with ten (31.3 %) in the conventional group (p = 0.015). CONCLUSION: This new technique offers shorter surgical and postoperative drainage time, shorter hospital stays, and fewer complications than conventional c-VATS upper left lobectomy.
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Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Arteria Pulmonar/cirugía , Cirugía Torácica Asistida por Video/métodos , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Drenaje , Femenino , Humanos , Tiempo de Internación , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Neoplasia Residual , Tempo Operativo , Estudios RetrospectivosRESUMEN
The aim of the present study was to detect the expression of survivin in human lung cancer and to investigate the influence of its downregulation on the biological behavior of A549 lung cancer cells. The high expression of survivin in human lung cancer was verified by immunohistochemistry. Survivin small interfering RNA (siRNA) and unrelated sequence were synthesized and the siRNA lentiviral vector was constructed. The vector was transfected into A549 lung cancer cells, in which the clone with stable expression was screened out. We blocked the expression of survivin mRNA and protein by RNA interference (RNAi) technique. The downregulation of survivin mRNA and protein expression was confirmed by real-time quantitative PCR and western blotting. The proliferative activity and growth rate of A549 cells were determined by colony formation assay and mononuclear cell direct cytotoxicity assay (MTT assay). The reconstituted basement membrane (RBM) penetrating capacity was determined by cell invasion assay. The cell movement and migratory capacity were detected by wound-healing repair assay. The results showed that the sequence-specific siRNA significantly downregulated the expression of survivin at both the mRNA and protein levels. Downregulation of survivin expression dramatically decreased the invasive and metastatic capacities of the cells, suppressed the proliferation, decelerated the rate of growth, reduced the number of clones on soft agar and decreased the capacity of RBM penetration and migration. In conclusion, survivin, which plays an important role in carcinogenesis and development of lung cancer, can be effectively downregulated using the RNAi technique.
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OBJECTIVE: To summarize early experience in combined thoraco-laparoscopic esophagectomy with two-field lymph node dissection for esophageal carcinoma. METHODS: A total of 150 patients with thoracic esophageal cancer who underwent combined thoracoscopic and laparoscopic esophagectomy in Union Hospital, Fujan Medical University, were enrolled in this study. RESULTS: Locations of the tumors included upper esophagus (n=14), middle esophagus (n=95), and lower esophagus (n=41). Pathological type showed squamous cell cancer (n=142) and other types of cancer (n=8). There was no intraoperative death. Conversion to open thoracotomy was required in 6 patients and conversion to open laparotomy in 2 patients. The average total operative time was( 258±45) min. The average operative thoracoscopic time was (140±33) min. The average time for gastric mobilization and neck esophagogastric anastomosis was (119±28) min. The average blood loss during the procedure was (207±130) ml. The average number of harvested lymph node with the specimen was 23.3±8.2. The tumor staging included stage I (n=39), II (n=58) and III (n=53). Postoperative complications occurred in 48(32%) patients including pneumonia (n=17), recurrent laryngeal injury (n=13), anastomotic leak (n=9), arrhythmias (n=9), chyle chest (n=5), delayed gastric emptying (n=5), ileus (n=2), volvulus (n=1), and thrombocytopenia (n=1). Two patients died postoperatively due to respiratory failure resulting from pneumonia. CONCLUSION: Thoraco-laparoscopic two-field lymph node dissection of esophageal cancer is a feasible minimally invasive approach.
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Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Toracoscopía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Survivin and Bcl-2 are generally considered to be inhibitors of apoptosis and are frequently overexpressed in several types of human cancers. However, their role in regulating the biological behavior of non-small cell lung carcinoma (NSCLC) remains controversial. We aimed to determine the expression of survivin and Bcl-2 and explore their correlation with clinicopathological features and prognosis. The expression of survivin and Bcl-2 proteins in 62 specimens of NSCLC tissues and 30 specimens of tumor adjacent tissues was detected using immunohistochemistry. The correlation between protein expression and clinicopathological features and prognosis was analyzed. The percentage of survivin-positive samples obtained from NSCLC tissues was 58.06% (36/62), which was significantly higher compared to that in normal lung tissues (10%, 3/30; P<0.05). Similarly, the percentage of Bcl-2-positive samples obtained from NSCLC tissues was statistically higher compared to that from normal lung tissues (51.61%, 32/62 vs. 6.67%, 2/30; P<0.05). Survivin expression was closely correlated with tumor differentiation, lymph node metastasis and TNM stage (P<0.05), while Bcl-2 expression was only associated with TNM stage (P<0.05). The expression of survivin was positively correlated with that of Bcl-2 (P<0.05). A five-year follow-up study revealed that the expression of survivin and Bcl-2 was negatively correlated with post-operative survival duration. Our findings suggest that survivin and Bcl-2 may act synergistically in the occurrence, development, invasion and metastasis of NSCLC, both of which are up-regulated in NSCLC tissues. The co-expression of survivin and Bcl-2, which is closely related to malignancy, may serve as a biomarker for predicting prognosis.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas Inhibidoras de la Apoptosis/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Proteínas Inhibidoras de la Apoptosis/genética , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/genética , SurvivinRESUMEN
The survivin protein, a member of the inhibitors of apoptosis (IAP) family, has gained popularity as a therapeutic target for cancer due to its selective expression in tumor cells and its significant involvement in tumor cell viability. The aim of this study was to investigate the effect of the survivin-small interfering RNA (siRNA) plasmid on survivin expression in the human lung cancer cell line, A549, and to observe its effects on apoptosis and proliferation of A549 cells. A549 human lung cancer cells were transfected with survivin-targeting siRNA. The downregulation of survivin expression was determined by real-time polymerase chain reaction and western blotting. The proliferation of A549 cells was determined by MTT assay. The apoptotic rate and cell cycle distribution were analyzed by flow cytometry (FCM). Caspase-9 activity was also detected to study the apoptosis of lung cancer cells induced by siRNA against survivin. The sequence-specific siRNA efficiently and specifically downregulated the expression of survivin at both the mRNA and protein levels. Downregulation of survivin expression dramatically suppressed the proliferation of A549 cells and arrested the cells at the G (1)/G (0) phase. Caspase-9 activity was significantly increased in A549 cells transfected with siRNA against survivin. In this study, we found that survivin-specific siRNA can efficiently suppress the expression of survivin, increase apoptosis and inhibit A549 cell proliferation. Our findings further indicate the possibility that the antitumor effects of survivin-siRNA are mediated through the activation of caspase-9.
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Apoptosis , Regulación hacia Abajo , Proteínas Inhibidoras de la Apoptosis/antagonistas & inhibidores , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Proliferación Celular , Puntos de Control de la Fase G1 del Ciclo Celular , Humanos , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , SurvivinRESUMEN
BACKGROUND & OBJECTIVE: Intrapleural hyperthermic perfusion is the distinctive therapy of malignant pleural effusion (MPE) caused by lung carcinoma. The expression pattern of T helper type 1 (Th1)/Th2 is an important index that reflects antitumor immunologic function. This study was to evaluate the therapeutic effect of intrapleural hyperthermic perfusion on MPE, and to investigate the impact of intrapleural hyperthermic perfusion on the immunologic reaction state of lung carcinoma patients with MPE by observing the expression pattern of cytokines Th1/Th2. METHODS: A total of 24 lung carcinoma patients with MPE underwent intrapleural hyperthermic perfusion with 43 celsius warmed normal saline for 60 min under video-assisted thoracoscopic surgery (VATS). The responses of pleural effusion, adverse events, life quality and survival time were observed. The concentrations of Th1/Th2-related cytokines interferon-gamma (IFN-gamma), interleukin-2 (IL-2)/IL-4, and IL-10 in peripheral blood and pleural effusion were detected by ELISA, and their mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Neither operation-related death nor postoperative complication occurred. The total response rate of pleural effusion control was 100%, including 23 cases of complete remission (CR) and 1 case of partial remission (PR). No recurrence of MPE occurred. The quality of life of all patients had been improved. The median survival time was 18.3 months. The 1-and 2-year survival rates were 91.7% and 16.7%. The concentrations and positive rates of IL-2 and IFN-gamma were significantly lower and those of IL-4 and IL-10 were significantly higher in peripheral blood and pleural effusion before hyperthermia than in those after hyperthermia (P<0.05). CONCLUSIONS: Intrapleural hyperthermic perfusion under VATS is a safe and effective treatment for MPE caused by lung carcinoma. It can convert the predominant state of Th2 cytokines in lung carcinoma patients with MPE to that of Th1 cytokines.
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Citocinas/genética , Hipertermia Inducida , Neoplasias Pulmonares/terapia , Derrame Pleural Maligno/terapia , Células TH1/inmunología , Células Th2/inmunología , Adulto , Anciano , Femenino , Humanos , Neoplasias Pulmonares/inmunología , Masculino , Persona de Mediana Edad , Derrame Pleural Maligno/inmunología , ARN Mensajero/análisisRESUMEN
OBJECTIVE: To discuss the application value of video-assisted thoracoscopic surgery (VATS) in treatment of esophageal leiomyoma. METHOD: Clinical data of patients with esophageal leiomyoma treated by VATS from January 1999 to August 2007 were analyzed. RESULTS: VATS esophageal leiomyoma enucleations were performed successfully in 23 patients, and 18 patients of them were performed by pure VATS, 5 patients of them were performed with mini-thoracotomy. All the procedures of operations were completed smoothly without mortality and postoperative complications. 22 patients were pathologically diagnosed as esophageal leiomyoma after surgery (2 patients' leiomyoma came from muscularis mucosa). 1 patient was esophageal muscularis neurilemmoma. CONCLUSION: VATS leiomyoma enucleations must be a routine operation while treat thoracic esophageal leiomyoma.
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Neoplasias Esofágicas/cirugía , Leiomioma/cirugía , Cirugía Torácica Asistida por Video/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND & OBJECTIVE: It is still very difficult to make a definite diagnosis for some mediastinal diseases through some examinations, such as CT scan and fibrobronchoscopy. To judge the metastasis of mediastinal lymph nodes exactly for lung cancer patients and make proper staging of lung cancer are important for defining therapeutic schedule and estimating prognosis. This study was to explore the application value and summarize the experience of mediastinoscopy in the diagnosis of mediastinal diseases and the staging of lung cancer with enlarged mediastinal lymph nodes. METHODS: Mediastinoscopy and biopsy were performed in 16 patients with different mediastinal diseases detected by imaging examinations and 14 lung cancer patients with enlarged mediastinal lymph nodes diagnosed by CT scan, PET, or fibrobronchoscopy. The staging of lung cancer was identified according to pathologic diagnosis. RESULTS: Of the 16 patients with different mediastinal diseases clarified by mediastinoscopy, 5 had nodule diseases, 3 had mediastinal lymph node tuberculosis, 2 had mediastinal lymphnoditis, 2 had lymphoma, 1 had extra-gastrointestinal type gastrointestinal malignant interstitialoma,1 had thymoma, 1 had metastatic small cell carcinoma, and 1 had metastatic adenocarcinoma. Of the 14 lung cancer patients with enlarged mediastinal lymph nodes, 6 had metastatic lymph nodes, and 8 had not; all of the 14 cases were accurately staged and received successful operations without severe postoperative complications. CONCLUSION: Mediastinoscopy is a safe, accurate and effective procedure for the diagnosis of mediastinal diseases and the staging of lung cancer.
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Neoplasias Pulmonares/diagnóstico , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Enfermedades del Mediastino/diagnóstico , Mediastinoscopía/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Escisión del Ganglio Linfático , Metástasis Linfática/patología , Masculino , Enfermedades del Mediastino/patología , Enfermedades del Mediastino/cirugía , Mediastino/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Tuberculosis Ganglionar/diagnóstico , Tuberculosis Ganglionar/patología , Tuberculosis Ganglionar/cirugía , Adulto JovenRESUMEN
OBJECTIVE: To investigate the feasibility of ex vivo adenovirus-mediated gene transfer of human interleukin10 (hIL10) via the pulmonary vein into lung isografts, and to investigate the effect of hIL-10 gene transfer on subsequent ischemia-reperfusion injury (IRI). METHODS: Fifty-six male SD rats were randomly divided into 4 equal groups: Group D, undergoing left lung isotransplantation with the improved cuff anastomosis technique (the Isografts were transvascularly transfected 5 ml of 5 x 10(9) plaque-forming units/ml adenovec-hIL-10 complex, Group C, with the Isografts transvascularly transfected with blank adenovirus vector Adenovec, Group B, with the Isografts transvascularly transfected with diluent , and Group A, undergoing sham operation. All allografts were preserved for 3 hours at 10 degrees C before transplantation. Four hours after reperfusion blood samples were collected from hr abdominal aorta to undergo blood air analysis. Lung function was evaluated by partial pressure of oxygen (PaO2). Then the rats were killed with their left lung taken out to undergo pathological examination. The graft lung wet-to-dry (W/D) weight ratio was measured. SABC immunohistochemistry was used to detect the expression of hIL-10 in the cytoplasm. ELISA was used to detect the expression of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). The levels of malonyldialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured by. Pathological morphologic change was also analyzed. RESULTS: The PaO2 level of Group D was significantly higher than those of Groups B and C (both P < 0.01). The W/D ratio, and levels of MDA and MPO of Group D were significantly lower than those of Groups B and C (both P < 0.01), but the SOD level of Group D was significantly higher than those of Groups B and C (both P < 0.05). The TNF-alpha and IFN-gamma levels of Group D were significantly lower than those of Groups B and C (both P < 0.01). Fewer tissue edema and interstitial inflammation were found in lungs. Of Group D RT-PCR showed hIL-10 expression in the lungs of the rats of Group D, but not in other groups. CONCLUSION: Ex vivo adenovirus-mediated gene transfer of hIL-10 via the pulmonary vein into the lung isografts is feasible and effective. hIL-10 gene transfer into lung isografts ameliorates subsequent IRI and improves early posttransplant graft function.