General Hospital of CPLA

Beijing, China

General Hospital of CPLA

Beijing, China

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Zhao Y.-F.,First Affiliated Hospital of the General Hospital of CPLA | Zhao J.-Y.,First Affiliated Hospital of the General Hospital of CPLA | Yue H.,First Affiliated Hospital of the General Hospital of CPLA | Hu K.-S.,General Hospital of CPLA | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2015

Forkhead transcription factors are essential for diverse processes in early embryonic development and organogenesis. As a member of the forkhead family, FOXD1 is required during kidney development and its inactivation results in failure of nephron progenitor cells. However, the role of FOXD1 in carcinogenesis and progression is still limited. Here, we reported that FOXD1 is a potential oncogene in breast cancer. We found that FOXD1 is up-regulated in breast cancer tissues. Depletion of FOXD1 expression decreases the ability of cell proliferation and chemoresistance in MDA-MB-231 cells, whereas overexpression of FOXD1 increases the ability of cell proliferation and chemoresistance in MCF-7 cells. Furthermore, we observed that FOXD1 induces G1 to S phase transition by targeting p27 expression. Our results suggest that FOXD1 may be a potential therapy target for patients with breast cancer. © 2014 Elsevier Inc. All rights reserved.


Dai G.-H.,General Hospital of CPLA | Shi V.,General Hospital of CPLA | Chen L.,General Hospital of CPLA | Lv Y.-L.,General Hospital of CPLA | Zhong M.,General Hospital of CPLA
Hepato-Gastroenterology | Year: 2012

Background/Aims: This study evaluates the efficacy and safety of trastuzumab combined with docetaxel-based chemotherapy in previously treated metastatic gastric carcinoma of Chinese patients with HER2 over-expression. Methodology: Twenty-two metastatic gastric cancer patients with HER2 over-expression (3+ by immunohistochemistry or HER2 amplification by fluorescence in situ hybridization) previously treated with 5-fluorouracil-based chemotherapy were eligible. Trastuzumab was administrated at 8mg/kg as a loading dose followed by 6mg/kg every 21 days. Docetaxel-based chemotherapy regimens were also given every 21 days. Results: Median age was 56 years. ECOG performance status was 0-2. Thirteen patients (59.1%) achieved partial response (PR) and 7 patients (31.8%) had stable disease (SD). Median progression free survival was 6.8 months and the median overall survival was 16.0 months. A patient with 3+ HER2 expression and HER2 gene amplification achieved PR after 6 cycles of combined treatment and received operation. Interestingly, his HER2 expression status in tumor tissue turned into negative after operation and he was still alive without progression until now. Trastuzumab combined with docetaxelbased chemotherapy was well tolerated. Grade 3-4 hematological toxicities were leucopenia (31.8%), neutropenia (18.2%) thrombocytopenia (9.1%) and anemia (4.5%). No unexpected toxicities, treatment-related deaths and symptomatic congestive heart failure were observed. Conclusions: Combinations of trastuzumab plus docetaxel-based regimens were well tolerated and effective in previously treated metastatic gastric cancer of Chinese patients with HER2 over-expression or gene amplification. © H.G.E. Update Medical Publishing S.A.


Shi Y.,General Hospital of CPLA | Chen L.,General Hospital of CPLA | Li J.,General Hospital of CPLA | Lv Y.-L.,General Hospital of CPLA | And 3 more authors.
Tumor Biology | Year: 2011

Ras/ERK and PI3K/Akt pathways are reported to play a prognostic role and contribute to drug resistance in many cancers. The objective of this study was to explore associations between the expression levels of several molecules in Ras/ERK and PI3K/Akt pathways and their clinical significance in predicting the effectiveness of postoperative adjuvant chemotherapy in patients with non-small cell lung cancer (NSCLC). The expressions of K-ras, Raf-1, ERK1/2, phosphorylated ERK1/2 (pERK1/2), Akt-1, phosphorylated Akt-1 (pAkt-1), and Bcl-2 were detected by immunohistochemistry in tumor specimens from 144 NSCLC patients. The correlations between the expression levels of these molecules and the clinicopathological characteristics were analyzed. Patient survival was analyzed by Kaplan-Meier method, log-rank test, and Cox regression. The positive expression rates of K-ras, Raf-1, ERK1/ 2, pERK1/2, Akt-1, pAkt-1, and Bcl-2 were 21.5%, 41.7%, 59.7%, 27.1%, 50.7%, 36.1%, and 30.6%, respectively. Univariate analysis showed that patients with pERK1/2-positive (P=0.01), Bcl-2-positive (P=0.023), or pAkt-1 negative (P=0.021) had significantly better recurrence-free survival (RFS) than those with pERK1/2-negative, Bcl-2-negative, or pAkt-1-positive. Multivariate analysis showed that earlier stage (P≤0.001), non-adenocarcinoma (P≤0.001), pERK1/2-positive (P≤0.001), and pAkt-1-negative (P=0.016) were independent prognostic factors for a better RFS in NSCLC. pERK1/2-positive and pAkt-1-negative proved to contribute to a better RFS in postoperative NSCLC patients who received adjuvant chemotherapy after taking the stage and histological subtype into account. pERK1/2 and pAkt-1 could be considered as new independent prognostic biomarkers for predicting RFS and selecting patients who are more likely to benefit from postoperative adjuvant chemotherapy. © International Society of Oncology and BioMarkers (ISOBM) 2010.


Shi Y.,General Hospital of CPLA | Qin R.,General Hospital of CPLA | Wang Z.-K.,General Hospital of CPLA | Dai G.-H.,General Hospital of CPLA
OncoTargets and Therapy | Year: 2013

Esophageal cancer is a major health hazard in many parts of the world and is often diagnosed late. The objective of this study was to explore the effcacy and safety of nanoparticle albumin-bound paclitaxel (Nab-PTX) combined with cisplatin (DDP) in patients with metastatic esophageal squamous cell carcinoma (ESCC). Patients with histologically confrmed ESCC were treated with Nab-PTX 250 mg/m2 and DDP 75 mg/m2 intravenously on day 1, every 21 days. Evaluation was performed after every two cycles of therapy and the therapy was continued until disease progression or unacceptable toxicity. From April 2010 to December 2012, 33 patients were enrolled. Ten patients had recurrent and metastatic tumors after surgery and 23 patients were diagnosed with unresectable metastatic disease. Patients received a median of four cycles of therapy (ranging from two to six cycles). Twenty patients achieved partial response and nine patients achieved stable disease; no complete response was observed. The objective response rate was 60.6% and the disease control rate was 87.9%. The median progression-free survival was 6.2 months (95% confdence interval: 4.0 to 8.4 months) and the median overall survival was 15.5 months (95% CI: 7.6 to 23.4 months). Only four patients experienced grade 3 adverse events, including vomiting, neutropenia, and sensory neuropathy. The most common adverse events were nausea/vomiting (81.8%), neutropenia (63.6%), leucopenia (48.5%), anemia (24.2%) and sensory neuropathy (24.2%). In conclusion, the combination of Nab-PTX and DDP is a highly effective and well-tolerated first-line treatment in metastatic ESCC. © 2013 Shi et al, publisher and licensee Dove Medical Press Ltd.


Yan S.,General Hospital of CPLA | Shun-Chang J.,General Hospital of CPLA | Li C.,General Hospital of CPLA | Jie L.,General Hospital of CPLA | And 2 more authors.
BMC Cancer | Year: 2010

Background: Adjuvant chemotherapy has been shown to improve survival rates of postoperative patients with non-small cell lung cancer (NSCLC). Biomarkers could help select an appropriate chemotherapy for NSCLC patients or predict the efficacy of chemotherapy. The objective of this study was to explore the possible prognostic and predictive role of topoisomerase II alpha (TopIIα) expression level in postoperative NSCLC patients who received adjuvant chemotherapy.Methods: Patients with stage I-III NSCLC, who underwent surgery in our hospital from January 2004 to December 2007 and who also received adjuvant chemotherapy after surgery, were analyzed in this study. Expression of TopIIα and Ki67 in paraffin-embedded tissues was detected by immunohistochemistry (IHC). The relationships between clinicopathological characteristics, chemotherapy regimens, the expression of biomarkers and disease free survival (DFS) were analyzed.Results: TopIIα and Ki67 were highly expressed in 22.5% and 36.4% of the 151 patients, respectively. Univariate survival analysis showed that male sex (P = 0.036), non-adenocarcinoma (P = 0.004), earlier pathological TNM stage (P = 0.001) or pathological N stage (P < 0.001), and high expression of TopIIα (P = 0.012) were correlated with better DFS, whereas age, smoking history, different chemotherapy regimens, T stage and expression level of Ki67 were of no prognostic significance. Further stratified analysis showed that vinorelbine (NVB)-containing adjuvant regimens were generally associated with better DFS than regimens without NVB in patients with low TopIIα expression, though the difference was not statistically significant (P = 0.065). Pairwise comparisons for patients with low TopIIα expression indicated that the NVB-containing regimen was associated with better DFS than the docetaxel (TXT)-containing regimen (P = 0.047). COX multivariate analysis showed that pathological TNM stage, histological subtype and expression level of TopIIα to be independent of risk factors affecting DFS in postoperative NSCLC patients who received chemotherapy.Conclusions: High TopIIα expression was discovered to be correlated with better DFS for postoperative NSCLC patients who received adjuvant chemotherapy. The NVB-containing chemotherapy regimen was more effective than the TXT-containing regimen in improving DFS in patients with low TopIIα expression. TopIIα could be considered to be an independent prognostic biomarker of DFS in postoperative NSCLC patients who received adjuvant chemotherapy. © 2010 Yan et al; licensee BioMed Central Ltd.


PubMed | General Hospital of CPLA
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2011

Ras/ERK and PI3K/Akt pathways are reported to play a prognostic role and contribute to drug resistance in many cancers. The objective of this study was to explore associations between the expression levels of several molecules in Ras/ERK and PI3K/Akt pathways and their clinical significance in predicting the effectiveness of postoperative adjuvant chemotherapy in patients with non-small cell lung cancer (NSCLC). The expressions of K-ras, Raf-1, ERK1/2, phosphorylated ERK1/2 (pERK1/2), Akt-1, phosphorylated Akt-1 (pAkt-1), and Bcl-2 were detected by immunohistochemistry in tumor specimens from 144 NSCLC patients. The correlations between the expression levels of these molecules and the clinicopathological characteristics were analyzed. Patient survival was analyzed by Kaplan-Meier method, log-rank test, and Cox regression. The positive expression rates of K-ras, Raf-1, ERK1/2, pERK1/2, Akt-1, pAkt-1, and Bcl-2 were 21.5%, 41.7%, 59.7%, 27.1%, 50.7%, 36.1%, and 30.6%, respectively. Univariate analysis showed that patients with pERK1/2-positive (P=0.01), Bcl-2-positive (P=0.023), or pAkt-1 negative (P=0.021) had significantly better recurrence-free survival (RFS) than those with pERK1/2-negative, Bcl-2-negative, or pAkt-1-positive. Multivariate analysis showed that earlier stage (P0.001), non-adenocarcinoma (P0.001), pERK1/2-positive (P0.001), and pAkt-1-negative (P=0.016) were independent prognostic factors for a better RFS in NSCLC. pERK1/2-positive and pAkt-1-negative proved to contribute to a better RFS in postoperative NSCLC patients who received adjuvant chemotherapy after taking the stage and histological subtype into account. pERK1/2 and pAkt-1 could be considered as new independent prognostic biomarkers for predicting RFS and selecting patients who are more likely to benefit from postoperative adjuvant chemotherapy.


Esophageal cancer is a major health hazard in many parts of the world and is often diagnosed late. The objective of this study was to explore the efficacy and safety of nanoparticle albumin-bound paclitaxel (Nab-PTX) combined with cisplatin (DDP) in patients with metastatic esophageal squamous cell carcinoma (ESCC). Patients with histologically confirmed ESCC were treated with Nab-PTX 250 mg/m(2) and DDP 75 mg/m(2) intravenously on day 1, every 21 days. Evaluation was performed after every two cycles of therapy and the therapy was continued until disease progression or unacceptable toxicity. From April 2010 to December 2012, 33 patients were enrolled. Ten patients had recurrent and metastatic tumors after surgery and 23 patients were diagnosed with unresectable metastatic disease. Patients received a median of four cycles of therapy (ranging from two to six cycles). Twenty patients achieved partial response and nine patients achieved stable disease; no complete response was observed. The objective response rate was 60.6% and the disease control rate was 87.9%. The median progression-free survival was 6.2 months (95% confidence interval: 4.0 to 8.4 months) and the median overall survival was 15.5 months (95% CI: 7.6 to 23.4 months). Only four patients experienced grade 3 adverse events, including vomiting, neutropenia, and sensory neuropathy. The most common adverse events were nausea/vomiting (81.8%), neutropenia (63.6%), leucopenia (48.5%), anemia (24.2%) and sensory neuropathy (24.2%). In conclusion, the combination of Nab-PTX and DDP is a highly effective and well-tolerated first-line treatment in metastatic ESCC.


PubMed | General Hospital of CPLA
Type: Clinical Trial | Journal: Hepato-gastroenterology | Year: 2013

This study evaluates the efficacy and safety of trastuzumab combined with docetaxel-based chemotherapy in previously treated metastatic gastric carcinoma of Chinese patients with HER2 over-expression.Twenty-two meta-static gastric cancer patients with HER2 over-expression (3+ by immunohistochemistry or HER2 amplification by fluorescence in situ hybridization) previously treated with 5-fluorouracil-based chemotherapy were eligible. Trastuzumab was administrated at 8mg/kg as a loading dose followed by 6mg/kg ev-ery 21 days. Docetaxel-based chemotherapy regimens were also given every 21 days.Median age was 56 years. ECOG performance status was 0-2. Thir-teen patients (59.1%) achieved partial response (PR)and 7 patients (31.8%) had stable disease (SD). Median progression free survival was 6.8 months and the median overall survival was 16.0 months. A patient with 3+ HER2 expression and HER2 gene amplification achieved PR after 6 cycles of combined treatment and received operation. Interestingly, his HER2 expression status in tumor tissue turned into negative after operation and he was still alive without progression until now. Trastuzumab combined with docetaxel-based chemotherapy was well tolerated. Grade 3-4 hematological toxicities were leucopenia (31.8%), neutropenia (18.2%) thrombocytopenia (9.1%) and ane-mia (4.5%). No unexpected toxicities, treatment-related deaths and symptomatic congestive heart failure were observed.Combinations of trastuzumab plus docetaxel-based regimens were well tolerated and effective in previously treated metastatic gastric cancer of Chinese patients with HER2 over-expression or gene amplification.


Adjuvant chemotherapy has been shown to improve survival rates of postoperative patients with non-small cell lung cancer (NSCLC). Biomarkers could help select an appropriate chemotherapy for NSCLC patients or predict the efficacy of chemotherapy. The objective of this study was to explore the possible prognostic and predictive role of topoisomerase II alpha (TopII) expression level in postoperative NSCLC patients who received adjuvant chemotherapy.Patients with stage I-III NSCLC, who underwent surgery in our hospital from January 2004 to December 2007 and who also received adjuvant chemotherapy after surgery, were analyzed in this study. Expression of TopII and Ki67 in paraffin-embedded tissues was detected by immunohistochemistry (IHC). The relationships between clinicopathological characteristics, chemotherapy regimens, the expression of biomarkers and disease free survival (DFS) were analyzed.TopII and Ki67 were highly expressed in 22.5% and 36.4% of the 151 patients, respectively. Univariate survival analysis showed that male sex (P = 0.036), non-adenocarcinoma (P = 0.004), earlier pathological TNM stage (P = 0.001) or pathological N stage (P < 0.001), and high expression of TopII (P = 0.012) were correlated with better DFS, whereas age, smoking history, different chemotherapy regimens, T stage and expression level of Ki67 were of no prognostic significance. Further stratified analysis showed that vinorelbine (NVB)-containing adjuvant regimens were generally associated with better DFS than regimens without NVB in patients with low TopII expression, though the difference was not statistically significant (P = 0.065). Pairwise comparisons for patients with low TopII expression indicated that the NVB-containing regimen was associated with better DFS than the docetaxel (TXT)-containing regimen (P = 0.047). COX multivariate analysis showed that pathological TNM stage, histological subtype and expression level of TopII to be independent of risk factors affecting DFS in postoperative NSCLC patients who received chemotherapy.High TopII expression was discovered to be correlated with better DFS for postoperative NSCLC patients who received adjuvant chemotherapy. The NVB-containing chemotherapy regimen was more effective than the TXT-containing regimen in improving DFS in patients with low TopII expression. TopII could be considered to be an independent prognostic biomarker of DFS in postoperative NSCLC patients who received adjuvant chemotherapy.

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