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Sun S.,Shanghai Ruijin Hospital | Sun S.,Linyi Peoples Hospital | Fei X.,Shanghai Ruijin Hospital | Mao Y.,Shanghai Ruijin Hospital | And 11 more authors.
Cancer Immunology, Immunotherapy | Year: 2014

The programmed death-1 (PD-1) molecule is mainly expressed on functionally "exhausted" CD8+ T cells, dampening the host antitumor immune response. We evaluated the ratio between effective and regulatory T cells (Tregs) and PD-1 expression as a prognostic factor for operable breast cancer patients. A series of 218 newly diagnosed invasive breast cancer patients who had undergone primary surgery at Ruijin Hospital were identified. The influence of CD8+ cytotoxic T lymphocytes, FOXP3+ (Treg cell marker), and PD-1+ immune cell counts on prognosis was analyzed utilizing immunohistochemistry. Both PD-1+ immune cells and FOXP3+ Tregs counts were significantly associated with unfavorable prognostic factors. In bivariate, but not multivariate analysis, high tumor infiltrating PD-1+ cell counts correlated with significantly shorter patient survival. Our results suggest a prognostic value of the PD-1+ immune cell population in such breast cancer patients. Targeting the PD-1 pathway may be a feasible approach to treating patients with breast cancer. © 2014 Springer-Verlag.


Sun J.,Shanghai JiaoTong University | Teng J.,Shanghai JiaoTong University | Yang H.,Shanghai JiaoTong University | Li Z.,Shanghai JiaoTong University | And 4 more authors.
Annals of Thoracic Surgery | Year: 2013

Background Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure that has enabled mediastinal and hilar lymph node assessment with a high sensitivity, but its role in the diagnosis of intrathoracic tuberculosis (TB) has not been established. Methods We prospectively studied 59 patients suspected of having TB with thoracic lymph node lesions or intrapulmonary lesions accessible by EBUS-TBNA at a clinical center for thoracic medicine from January 2010 to December 2011. Bronchoscopic findings, EBUS-TBNA procedures, pathologic findings, and microbiologic results were recorded. Results Of 59 eligible patients, 41 patients had TB, 5 had lung cancer, 7 had inflammation, and 6 had sarcoidosis. Sensitivity was 85%, specificity was 100%, positive and negative predictive values were 100% and 75%, respectively, and accuracy was 90% by EBUS-TBNA for TB. Pathologic findings were consistent with TB in 80% of patients (33 of 41), and in 27% (11 of 41) the smear was positive. A total of 37 patients with TB had cultures, of whom 17 (46%) were positive. There were 80 mediastinal and hilar lymph nodes and 5 intrapulmonary lesions that were biopsied in the 41 patients with TB. Multivariate logistic regression revealed that short-axis diameter was an independent risk factor associated with positive pathology, smear, and culture (p < 0.05). Additionally, pathology showing necrosis was an independent risk factor associated with a positive culture. Conclusions Endobronchial ultrasound-guided transbronchial needle aspiration has a high diagnostic yield in the investigation of suspected intrathoracic TB by means of aspiration of intrathoracic lymph nodes and tracheobronchial wall-adjacent lung lesions. © 2013 by The Society of Thoracic Surgeons.


Sun J.,Shanghai JiaoTong University | Yang H.,Shanghai JiaoTong University | Teng J.,Shanghai JiaoTong University | Zhang J.,Shanghai JiaoTong University | And 3 more authors.
Annals of Thoracic Surgery | Year: 2015

Background Although the role of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) in pulmonary sarcoidosis has previously been investigated, the determining factors in diagnosing sarcoidosis by EBUS-TBNA without rapid on-site evaluation (ROSE) are unclear. Methods Patients with clinically and radiographically suspected sarcoidosis underwent EBUS-TBNA without ROSE in a prospective study. Presence of non-caseating epithelioid cell granulomas was pathologic evidence of sarcoidosis. Results The EBUS-TBNA was performed in 120 patients, 111 of whom had confirmed sarcoidosis. For the patients with sarcoidosis (62 stage I, 49 stage II) EBUS-TBNA provided sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 93.69%, 100%, 100%, 56.25%, and 94.17%, respectively, in the diagnosis of sarcoidosis. Diagnostic yield of EBUS-TBNA for sarcoidosis was associated with disease stage, but not associated with serum angiotensin converting enzyme level, number of lymph node stations sampled per patient, or total number of passes performed per patient. At EBUS-TBNA, 284 mediastinal and hilar lymph nodes were aspirated in 111 patients. Multivariate logistic regression revealed that short-axis diameter and more than 1 needle pass per lymph node were independent risk factors associated with positive pathology. No major procedure-related complications were observed. Conclusions Endobronchial ultrasound-guided transbronchial needle aspiration is a safe procedure with high sensitivity for diagnosing sarcoidosis, having a higher diagnostic yield in stage I than stage II. To obtain a higher diagnostic yield of EBUS-TBNA in pulmonary sarcoidosis without ROSE, operators should select the largest mediastinal or hilar lymph node accessible and puncture with 3 to 5 passes. © 2015 The Society of Thoracic Surgeons.


Sun J.,Shanghai JiaoTong University | Garfield D.H.,ProMed Cancer Centers Shanghai | Lam B.,Hong Kong Sanatorium and Hospital | Yan J.,Shanghai JiaoTong University | And 3 more authors.
Journal of Thoracic Oncology | Year: 2011

Objective: To compare the accuracy of autofluorescence bronchoscopy (AFB) combined with white light bronchoscopy (WLB) versus WLB alone in the diagnosis of lung cancer. Methods: The Ovid, PubMed, and Google Scholar databases from January 1990 to October 2010 were searched. Two reviewers independently assessed the quality of the trials and extracted data. The relative risk for sensitivity and specificity on a per-lesion basis of AFB + WLB versus WLB alone to detect intraepithelial neoplasia and invasive cancer were pooled by Review Manager. Results: Twenty-one studies involving 3266 patients were ultimately analyzed. The pool relative sensitivity on a per-lesion basis of AFB + WLB versus WLB alone to detect intraepithelial neoplasia and invasive cancer was 2.04 (95% confidence interval [CI] 1.72-2.42) and 1.15 (95% CI 1.05-1.26), respectively. The pool relative specificity on a per-lesion basis of AFB + WLB versus WLB alone was 0.65 (95% CI 0.59-0.73). Conclusions: Although the specificity of AFB + WLB is lower than WLB alone, AFB + WLB seems to significantly improve the sensitivity to detect intraepithelial neoplasia. However, this advantage over WLB alone seems much less in detecting invasive lung cancer. Copyright © 2011 by the International Association for the Study of Lung Cancer.


PubMed | ProMed Cancer Centers Shanghai and Shanghai JiaoTong University
Type: Evaluation Studies | Journal: The Annals of thoracic surgery | Year: 2015

Although the role of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) in pulmonary sarcoidosis has previously been investigated, the determining factors in diagnosing sarcoidosis by EBUS-TBNA without rapid on-site evaluation (ROSE) are unclear.Patients with clinically and radiographically suspected sarcoidosis underwent EBUS-TBNA without ROSE in a prospective study. Presence of non-caseating epithelioid cell granulomas was pathologic evidence of sarcoidosis.The EBUS-TBNA was performed in 120 patients, 111 of whom had confirmed sarcoidosis. For the patients with sarcoidosis (62 stage I, 49 stage II) EBUS-TBNA provided sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 93.69%, 100%, 100%, 56.25%, and 94.17%, respectively, in the diagnosis of sarcoidosis. Diagnostic yield of EBUS-TBNA for sarcoidosis was associated with disease stage, but not associated with serum angiotensin converting enzyme level, number of lymph node stations sampled per patient, or total number of passes performed per patient. At EBUS-TBNA, 284 mediastinal and hilar lymph nodes were aspirated in 111 patients. Multivariate logistic regression revealed that short-axis diameter and more than 1 needle pass per lymph node were independent risk factors associated with positive pathology. No major procedure-related complications were observed.Endobronchial ultrasound-guided transbronchial needle aspiration is a safe procedure with high sensitivity for diagnosing sarcoidosis, having a higher diagnostic yield in stage I than stage II. To obtain a higher diagnostic yield of EBUS-TBNA in pulmonary sarcoidosis without ROSE, operators should select the largest mediastinal or hilar lymph node accessible and puncture with 3 to 5 passes.


Xu N.,Fudan University | Zhang X.,Fudan University | Wang X.,Fudan University | Ge H.-Y.,Fudan University | And 5 more authors.
Acta Pharmacologica Sinica | Year: 2012

Aim: Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC), and the underlying mechanism remains unclear. FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients. In this study, we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms. Methods: Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used. mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis. RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells, and lentiviral infection was used to overexpress FoxM1 in H292 cells. MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells. Results: Treatment of SPC-A-1 cells with gefitinib (1 and 10mol/L) upregulated the expression of FoxM1 in time-and concentration-dependent manners, while gefitinib (1mol/L) downregulated in H292 cells. In SPC-A-1 cells treated with gefitinib (1mol/L), the expression of several downstream targets of FoxM1, including survivin, cyclin B1, SKP2, PLK1, Aurora B kinase and CDC25B, were significantly upregulated. Overexpression of FoxM1 increased the resistance in H292 cells, while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis.Conclusion:The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro. FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib. © 2012 CPS and SIMM. All rights reserved.

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