Key Laboratory of Cancer Prevention and Therapy

Tianjin, China

Key Laboratory of Cancer Prevention and Therapy

Tianjin, China
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Sun L.,Tianjin Medical University | Zhang Q.,Tianjin Medical University | Luan H.,Tianjin Medical University | Zhan Z.,Tianjin Medical University | And 3 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2011

Background. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have been widely used for the treatment of non-small cell lung cancer (NSCLC). KRAS and EGFR somatic mutations in NSCLC may predict resistance and responsiveness to TKI, respectively. Nevertheless, most research to date has been conducted on samples from primary tumors. For many patients with advanced disease, their samples can only be obtained from metastases for test. The molecular characteristics of metastasized tumors may be different from those of primary tumors. Materials and methods. Mutation status of KRAS and EGFR between primary tumors and local lymph node metastases of 80 Chinese patients with NSCLC were analyzed by direct sequencing. Five of them were given gefitinib as neoadjunvant treatment after the EGFR-TKI sensitive mutations were detected in their biopsies of mediastinal lymph nodes metastases. McNemar's test was used to compare the EGFR and KRAS mutation status between primary tumors and corresponding local lymph node metastases. Data evaluation was carried out with SPSS-13.0 statistical software. Results. Among the 160 samples, one primary tumor and seven metastases were identified with KRAS mutations and 21 primary tumors and 26 metastases were found to have EGFR mutations. KRAS and EGFR mutation status was different between primary tumors and corresponding metastases in 6 (7.5%) and 7 (8.75%) patients, respectively. One patient with no TKI sensitive mutations detected in the primary tumor showed disease progression. Conclusion. Our results suggest that a considerable proportion of NSCLC in Chinese population showed discrepancy in KRAS and EGFR mutation status between primary tumors and corresponding metastases. This observation may have important implication for the use of targeted TKI therapy in the treatment of NSCLC patients. © 2011 Sun et al; licensee BioMed Central Ltd.


Liu Y.,Tianjin Medical University | Liu Y.,Key Laboratory of Cancer Prevention and Therapy | Liu H.,Tianjin Central Hospital of Gynecology and Obstetrics | Bai X.,Tianjin Huanhu Hospital | And 4 more authors.
Gynecologic Oncology | Year: 2011

Objective: This study aims to determine the diagnostic value of diffusion-weighted imaging (DWI) in the differentiation of metastatic lymph nodes from non-metastatic lymph nodes in uterine cervical cancer. Methods: In 42 patients who underwent lymph node dissection for uterine cervical cancer, conventional MRI and DWI examinations were performed before surgery. Of the 1109 total dissected pelvic lymph nodes, 188 enlarged nodes with a short-axis diameter of 5 mm or greater were included for further analysis. Each of the size-based criteria (i.e., short-axis diameter and long-axis diameter) and ADC-based criteria (i.e., mean ADC, minimum ADC, mean rADC (relative ADC) and minimum rADC) were compared between metastatic lymph nodes and non-metastatic lymph nodes. Results: There were statistically significant differences between metastatic and non-metastatic lymph nodes in the short-axis diameter, long-axis diameter, mean ADC, minimum ADC, mean rADC and minimum rADC (P < 0.001). The Az of the minimum ADC (0.990) was greater than that of the other ADC-based criteria (0.974, 0.939, 0.976 for mean ADC, mean rADC and minimum rADC, respectively) and all size-based criteria (0.878 for short-axis diameter and 0.858 for long-axis diameter) (P < 0.05). Using the minimum ADC criteria (≤ 0.881 × 10- 3mm2/s), the sensitivity and specificity for differentiating metastatic from non-metastatic lymph nodes were 95.7% and 96.5%, respectively. Conclusions: DWI is feasible for differentiating metastatic from non-metastatic pelvic lymph nodes in patients with uterine cervical cancer and minimum ADC could be served as a representative marker. © 2011 Elsevier Inc. All rights reserved.


Lu S.,Tianjin Medical University | Lu S.,Key Laboratory of Cancer Prevention and Therapy | Wang Z.,Nanjing Medical University | Cui D.,Zhengzhou University | And 4 more authors.
Breast Cancer Research and Treatment | Year: 2011

Glutathione S-transferase P1 (GSTP1) is involved in a wide range of detoxifying reactions. Any alteration in the structure, function, or expression of GSTP1 gene may alter the ability of a cell to inactivate carcinogens or mutagens, and thus modify an individual's risk to cancer. Previous epidemiological studies on the potential association between GSTP1 Ile105Val polymorphism and breast cancer risk have produced inconsistent results. In order to drive a more precise estimation of this association, we performed a meta-analysis of 30 published case-control studies including 15,901 cases and 18,757 controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. The results of this meta-analysis showed that GSTP1 Ile105Val polymorphism was not associated with breast cancer susceptibility in overall population. However, in subgroup analysis by ethnicity, we found a significant association among Asian population (for Val/Val vs. Ile/Ile: OR 1.27, 95% CI 1.02-1.83; for the recessive model Val/Val vs. Ile/Ile + Ile/Val: OR 1.42, 95% CI 1.20-1.69). When stratified by study design, significantly elevated susceptibility to breast cancer was found among hospital-based studies (for Val/Val vs. Ile/Ile: OR 1.38, 95% CI 1.16-1.63; for recessive model Val/Val vs. Ile/Val + Ile/Ile: OR 1.31, 95% CI 1.12-1.55; for dominant model: Val/Val + Ile/Val vs. Ile/Ile: OR 1.10, 95% CI 1.02-1.19). In conclusion, our meta-analysis suggests that GSTP1 Ile105Val polymorphism may increase susceptibility to breast cancer in Asian population. © 2010 Springer Science+Business Media, LLC.


Chen Y.,Tianjin Medical University | Chen Y.,Key Laboratory of Cancer Prevention and Therapy | Zhang L.,Tianjin Medical University | Zhang L.,Key Laboratory of Cancer Prevention and Therapy | And 2 more authors.
Archives of Gynecology and Obstetrics | Year: 2013

Background: Ovarian cancer (OC) is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at advanced stage with poor prognosis. Currently, surgical tumor debulking followed by chemotherapy based on platinum and taxane is the standard treatment for advanced OC. However, these patients remain at great risk for recurrence and developing drug resistance. Therefore, new treatment strategies are needed to improve outcomes for patients with advanced and recurrent OC. Olaparib (AZD2281, KU-0059436), as one of the best understood Poly-(ADP-ribose) polymerase (PARP) inhibitor targeting DNA repair mechanisms, caused more and more attention. Clinical trial data of Olaparib had been cumulated, which applied as the single-agent in relapsed OC monotherapy, especially for BRCA mutation associated OC. Methods: In this review, we demonstrated the mechanism of PARP inhibitors and summarized clinical trial data and clinical development of Olaparib targeted OC in order to address a new promising therapy strategy for advanced relapsed OC. Conclusion: Given the unprecedented clinical potential of Olaparib, the further research on Olaparib will have great significance in selection of OC patient populations that will respond to treatment. © 2013 Springer-Verlag Berlin Heidelberg.


Fu X.,Tianjin Medical University | Fu X.,Key Laboratory of Cancer Prevention and Therapy | Tian J.,Tianjin Medical University | Zhang L.,Tianjin Medical University | And 3 more authors.
FEBS Letters | Year: 2012

The mechanisms underlying ovarian cancer cell resistance to cisplatin (CDDP) are not fully understood. MicroRNAs (miRNAs) play important roles in tumorigenesis and drug resistance. In this paper, we utilized microRNA array and real-time PCR to show that miR-93 is significantly up-regulated in cisplatin-resistant ovarian cancer cells. In vitro assays show that over-expression and knock-down of miR-93 regulate apoptotic activity, and thereby cisplatin chemosensitivity, in ovarian cells. Furthermore, we found that miR-93 can directly target PTEN, and participates in the regulation of the AKT signaling pathway. MiR-93 inversely correlates with PTEN expression in CDDP-resistant and sensitive human ovarian cancer tissues. These results may have implications for therapeutic strategies aiming to overcome ovarian cancer cell resistance to cisplatin. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Cui M.,Nankai University | Xiao Z.,Nankai University | Wang Y.,Nankai University | Zheng M.,Nankai University | And 6 more authors.
Cancer Research | Year: 2015

HULC is a long noncoding RNA overexpressed in hepatocellular carcinoma (HCC), but its functional contributions in this setting have not been determined. In this study, we explored the hypothesis that HULC contributes to malignant development by supporting abnormal lipid metabolism in hepatoma cells. HULC modulated the deregulation of lipid metabolism in HCC by activating the acyl-CoA synthetase subunit ACSL1. Immunohistochemical analysis of tissue microarrays revealed that approximately 77% (180/233) of HCC tissues were positive for ACSL1. Moreover, HULC mRNA levels correlated positively with ACSL1 levels in 60 HCC cases according to real-time PCR analysis. Mechanistic investigations showed that HULC upregulated the transcriptional factor PPARA, which activated the ACSL1 promoter in hepatoma cells. HULC also suppressed miR-9 targeting of PPARAmRNAby eliciting methylation of CpG islands in the miR-9 promoter. We documented the ability of HULC to promote lipogenesis, thereby stimulating accumulation of intracellular triglycerides and cholesterol in vitro and in vivo. Strikingly, ACSL1 overexpression that generates cholesterol was sufficient to enhance the proliferation of hepatoma cells. Further, cholesterol addition was sufficient to upregulate HULC expression through a positive feedback loop involving the retinoid receptor RXRA, which activated the HULC promoter. Overall, we concluded that HULC functions as an oncogene in hepatoma cells, acting mechanistically by deregulating lipid metabolism through a signaling pathway involving miR-9, PPARA, and ACSL1 that is reinforced by a feed-forward pathway involving cholesterol and RXRA to drive HULC signaling. © 2015 American Association for Cancer Research.


Zhou Z.,Nankai University | Liu F.,Tianjin Medical University | Liu F.,Key Laboratory of Cancer Prevention and Therapy | Zhang Z.-S.,Nankai University | And 5 more authors.
Cancer Research | Year: 2014

Intermittent oxygen deficiency in cancers promotes prolonged inflammation, continuous angiogenesis, and increased drug resistance. Hypoxia-inducible factor-1 (HIF1) has a pivotal role in the regulation of cellular responses to oxygen deficiency. The α-subunit of HIF1 (HIF1α) is degraded in normoxia but stabilized in hypoxia. However, the molecular mechanism that controls oxygen-independent degradation of HIF1α has remained elusive. Human rhomboid family-1 (RHBDF1) is a member of a large family of nonprotease rhomboids whose function is basically unknown. We report here that RHBDF1 expression in breast cancer is highly elevated and is strongly correlated with escalated disease progression, metastasis, poor prognosis, and poor response to chemotherapy. We show that RHBDF1 interaction with the receptor of activated protein-C kinase-1 (RACK1) in breast cancer cells prevents RACK1-Assisted, oxygen-independent HIF1α degradation. In addition, we show that the HIF1α-stabilizing activity of RHBDF1 diminishes when the phosphorylation of a tyrosine residue on the RHBDF1 molecule is inhibited. These findings are consistent with the view that RHBDF1 is a critical component of a molecular switch that regulates HIF1α stability in cancer cells in hypoxia and that RHBDF1 is of potential value as a new target for cancer treatment. © 2014 American Association for Cancer Research.


Wang X.,Tianjin Medical University | Wang X.,Key Laboratory of Cancer Prevention and Therapy | Jiang R.,Tianjin Medical University | Jiang R.,Key Laboratory of Cancer Prevention and Therapy | And 2 more authors.
Cell Biochemistry and Biophysics | Year: 2014

Despite the increasing incidence of combined small-cell lung cancer (C-SCLC) in recent years, there have not been many data on clinical prognostic factors predicting prognosis of C-SCLC patients. In present study, we sought pretreatment features especially basic laboratory parameters predicting survival of C-SCLC. We analyzed 613 small-cell lung cancer (SCLC) patients at our institution between January 2005 and December 2010. We identified 114 patients with C-SCLC. The pathologic and clinical characteristics of these patients were reviewed. Data of laboratory parameters obtained during regular examinations at diagnosis of these patients were examined. The Kaplan-Meier method was used to calculate the survival rate and depict the survival curves. The Cox regression model was used to analyze the independent factors affecting the overall survival (OS). These data were compared with the results obtained from our 499 pure SCLC patients who presented during the same time period. Of the 613 SCLC patients analyzed, 18.6 % of the patients presented with C-SCLC. No difference in OS was observed in patients with C-SCLC and patients with pure SCLC (P = 0.995). The Kaplan-Meier survival curves revealed that poor ECOG-PS (P < 0.001), extensive disease (P < 0.001), pathologic subtype of SC/LC (P < 0.001), not receiving surgery (P = 0.001), elevated serum lactate dehydrogenase (LDH) (P = 0.005), elevated NSE (P = 0.043), and elevated neutrophile-lymphocyte ratio (NLR) (P = 0.018) were associated with adverse prognosis of patients with C-SCLC. By multivariate analysis, OS was affected by ECOG-PS (hazard ratio 2.001, P = 0.012), disease extent (hazard ratio 3.406, P < 0.001), and NLR (hazard ratio 1.704, P = 0.030) in C-SCLC patients, while the risk factors that influenced the prognosis of the patients with pure SCLC were ECOG-PS (hazard ratio 2.132, P < 0.001), disease extent (hazard ratio 1.482, P < 0.001), and LDH (hazard ratio 1.811, P < 0.001). Patients with C-SCLC carry a similar prognosis than those with pure small-cell variety. Easily accessible pretreatment parameters such as NLR should be considered in defining the prognosis of C-SCLC patients besides disease extent and performance status. © 2014 Springer Science+Business Media New York.


Chen Y.,Key Laboratory of Cancer Prevention and Therapy | Hao J.,Tianjin Medical University | Ma W.,Tianjin Medical University | Tang Y.,Tianjin Medical University | And 2 more authors.
Journal of Gastrointestinal Surgery | Year: 2011

Background: The incidence of pancreatic cancer has increased in China in the last decade, though efforts have been made in early detection and multimodality treatment. The aim of this study is to describe the decade-based development in early diagnosis and treatment modalities, as well as outcome for patients with pancreatic ductal adenocarcinoma (PDAC) in a high-volume facility. Methods: All the PDAC patients underwent surgery between 1991 and 2009 and were selected from the database of TianJin Cancer Institute and Hospital. Decade-based changes in early diagnosis, treatment modalities, and outcome of the patients were retrospectively analyzed. Results: Of the 565 patients with PDAC, patients in this decade (n = 460) had better overall survival than those in the last decade (n = 105), median survival was 10 months and 3 months, respectively. Patients in this decade had significantly improved in (P < 0. 001) 2-year (14. 7%) and 5-year survival rates (3. 5%) as compared to those in the last decade (6. 7% and 3. 4%, respectively). Patients with metastasis at diagnosis in the last decade and this decade were 54% and 26% (P < 0. 001), respectively. More patients in this decade had underwent R0/R1 resection (33% vs 20%, P = 0. 010), chemotherapy (37% vs 12%, P < 0. 001), and radical resection (34% vs 21%, P = 0. 014) than those in the last decade. Conclusion: Patients operated on for PDAC in this decade had a better outcome than those in the last decade. Early detection, improved resection margin, and development in multimodality treatment contribute to this improvement. © 2011 The Society for Surgery of the Alimentary Tract.


Zhang W.,Tianjin Medical University | Zhang W.,Key Laboratory of Cancer Prevention and Therapy | Tian J.,Tianjin Medical University | Tian J.,Key Laboratory of Cancer Prevention and Therapy | And 2 more authors.
Tumor Biology | Year: 2014

Within tumor microenvironment, high-mobility group box protein 1 (HMGB1) and tumor-associated macrophages (TAMs) are able to influence ovarian cancer development and progression via facilitating tumor lymphatic metastasis. However, little is known about the association between HMGB1 and TAMs on lymphangiogenesis in epithelial ovarian cancer (EOC). To investigate the effect of HMGB1 and TAMs on lymphangiogenesis in EOC, immunohistochemistry was performed to determine the expressions of HMGB1, TAMs, and lymphatic vessel density (LVD) in a total of 108 ovarian tissue specimens. Then, the relationships between HMGB1 or TAMs and LVD were assessed by correlation test. In our in vitro study, TAMs were isolated from ascites of EOC patients. Effects of HMGB1, TAMs, and HMGB1 combining with TAMs on lymphatic endothelial cell (LEC) proliferation, migration, and the capillary-like tube formation were measured. Results showed that the expression of HMGB1 and the number of TAMs infiltration were overexpressed in malignant ovarian tumors compared with that in normal ovarian and were closely associated with lymph node metastasis. Positive correlations existed between HMGB1 expression or TAMs count and LVD determination. In an in vitro study, data demonstrated that either HMGB1 or TAMs could facilitate lymphangiogenesis by inducing LEC proliferation, migration, and capillary-like tube formation. Meanwhile, HMGB1 combining with TAMs may augment the pro-lymphangiogenic property. Our data suggest that either HMGB1 or TAMs could facilitate lymphangiogenesis, while HMGB1 coculture with TAMs may strengthen the pro-lymphangiogenic potential, which may serve as a therapeutic target for ovarian cancer. © 2013 International Society of Oncology and BioMarkers (ISOBM).

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