Key Laboratory of Breast Cancer Prevention and Therapy

Tianjin, China

Key Laboratory of Breast Cancer Prevention and Therapy

Tianjin, China
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Wang J.,Tianjin Medical University | Wang J.,Key Laboratory of Breast Cancer Prevention and Therapy | Wang J.,Tianjin Key Laboratory of Cancer Prevention and Therapy | Cao X.,Tianjin Huanghe Hospital
Chinese Journal of Clinical Oncology | Year: 2017

Objective: To evaluate the clinical value of ultrasound-guided core-needle biopsy (US-CNB) in the diagnosis of breast lesions under categories 4A to 4C of the second edition of the Breast Imaging Reporting and Data System (BI-RADS) ultrasound lexicon. Methods: The pathological characteristics of 355 patients with breast masses who underwent US-CNB in the Tianjin Medical University Cancer Institute and Hospital from March 2015 to October 2015 were retrospectively analyzed. Each patient was subjected to postoperative pathological examination to confirm diagnosis. Results: According to the US-CNB results, of the 355 patients, 235 were diagnosed with breast cancer, and 120 had benign lesions. Through postoperative pathological examination, 41 of the patients with benign lesions were confirmed to have breast cancer. The specificity of the US-CNB was 100% in all the categories of breast masses. The sensibilities of breast masses under BI-RADS categories 4A, 4B, and 4C were 62.50%, 82.46%, and 89.73%, respectively. The accuracies of the US-CNB in 4A, 4B, and 4C were 84.62%, 87.01%, and 90.74%, correspondingly. Of the 41 patients with false-negative results, 14 had intraductal carcinoma, 5 had intraductal papillary carcinoma, 3 had mucinous carcinoma, and 19 had invasive ductal carcinoma. Conclusion: US-CNB is a safe, reliable, and accurate early diagnostic method for breast masses under the 4B and 4C categories. However, the sensibility of US-CNB was extremely low in patients with breast masses under the 4A category. Thus, final diagnosis should be accomplished by combining US-CNB with mammography, MRI, or other testing methods. Meanwhile, US-CNB is not recommended for patients with intraductal papillary neoplasms diagnosed through ultrasonography.


Liu B.,Key Laboratory of Breast Cancer Prevention and Therapy | Liu B.,Tianjin Medical University | Qu J.,Key Laboratory of Breast Cancer Prevention and Therapy | Qu J.,Tianjin Medical University | And 10 more authors.
Oncotarget | Year: 2015

MiR-195 suppresses tumor growth and is associated with better survival outcomes in several malignancies including non-small cell lung cancer (NSCLC). Our previous study showed high miR-195 plasma levels associated with favorable overall survival of non-smoking women with lung adenocarcinoma. To further elucidate role of miR-195 in NSCLC, we conducted in vitro experiment as well as clinical studies in a cohort of 299 NSCLC samples. We demonstrated that miR-195 expression was lower in tumor tissues and was associated with poor survival outcome. Overexpression of miR-195 suppressed tumor cell growth, migration and invasion. We discovered that CHEK1 was a direct target of miR-195, which decreased CHEK1 expression in lung cancer cells. High expression of CHEK1 in lung tumors was associated with poor overall survival. Our results suggest that miR-195 suppresses NSCLC and predicts lung cancer prognosis.


Liu J.,Tianjin Medical University | Liu J.,Key Laboratory of Breast Cancer Prevention and Therapy | Liu J.,Key Laboratory of Cancer Prevention and Therapy in Tianjin | Mao Q.,Tianjin Medical University | And 14 more authors.
Chinese Journal of Cancer Research | Year: 2013

The purpose of this study was to identify and validate circulating microRNAs (miRNAs) in human plasma for use as breast cancer (BC) biomarkers and to analyze their relationship to clinicopathologic features and its preliminary biological function. Genome-wide expression profiling of miRNAs in BC was investigated by microarray analysis. miR-155 was up-regulated greater than two-fold in BC compared with Normal Adjacent Tissue (NAT), whereas let-7b, miR-381, miR-10b, miR-125a-5p, miR-335, miR-205 and miR-145 were down- regulated greater than two-fold. Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of BC patients compared to controls. Using real-time PCR (RT-PCR), we analyzed miR-205 and miR-155 in archived serum from 30 participants, 20 with breast cancer and 10 healthy people. miR-205 was down-regulated in BC patient serum while miR-155 was up-regulated. Furthermore, we analyzed the relationship between the expression levels of these two miRNAs and the clinicopathologic parameters of BC patients. High expression of miR155 was associated with clinical stage, molecular type, Ki-67 and p53 in BC patients (P<0.05). By contrast, we found no significant correlation between miR-205 and BC patient clinicopathologic parameters. Functional analysis showed that ectopic expression of miR-205 significantly inhibits cell proliferation and promotes apoptosis. miR-205 was down- regulated and miR-155 was up-regulated in BC patient serum. miR-155 was positive correlated with clinical stage and ki-67 and negatively correlated with p53 status. © Chinese Journal of Cancer Research. All rights reserved.


Xiao Y.,Tianhe Hospital | Zhang S.,Tianjin Medical University | Zhang S.,Key Laboratory of Breast Cancer Prevention and Therapy | Zhang S.,Key Laboratory of Cancer Prevention and Therapy | And 12 more authors.
Tumor Biology | Year: 2014

This study selected luminal-type breast cancer patients as the study subjects. The patients were divided into groups according to the presence of diabetes and the types of medication used, and the patients' clinicopathological characteristics and prognostic indicators were explored. A total of 5,785 patients with luminal-type breast cancer admitted to Tianjin Medical University Cancer Institute and Hospital between January 2002 and December 2006 were selected as the study subjects. The subjects included 680 breast cancer patients with diabetes and 5,105 breast cancer patients without diabetes. The patients were divided into Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes. Each subtype was further divided into a metformin group, a non-metformin group, and a nondiabetic group. The research indicators included breast cancer mortality, age, body mass index (BMI), amenorrhea, the presence of cardiovascular and cerebrovascular disease, pathological stage, pathological type, lymph node involvement, vessel carcinoma embolus, and the chemotherapy and endocrine regimen. A Kaplan-Meier analysis was conducted to analyze the differences in breast cancer mortality rates among the groups. The Cox proportional hazard model was adopted to detect independent factors related to prognosis. Kaplan-Meier univariate analysis showed that for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes, the cancer-specific mortality rates differed significantly among the metformin, non-metformin, and nondiabetic groups. The 5-year survival rates were 94 %, 82 %, and 91 % (P = 0.002); 93.5 %, 81 %, and 89 % (P < 0.001); and 84 %, 77 %, and 83 % (P = 0.035) for the subtypes within each group, respectively. Cox regression multivariate analysis showed that compared with the metformin group, all three subtypes of the, the non-metformin group showed poorer prognosis (hazard ratio [HR], 3.579; 95 % confidence interval [CI], 1.506-8.506 [P = 0.004]; HR, 3.232; 95 % CI, 1.839-5.678 [P < 0.001]; HR, 2.034; 95 % CI,1.019-4.059 [P = 0.044] for Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+, respectively). Compared with the metformin group, the diabetic group showed poorer prognosis only for the Luminal B (high ki67) subtype (HR, 1.762; 95 % CI, 1.033-3.005 [P = 0.038]). In addition, for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subgroups, there was a higher proportion of elderly patients (P < 0.001) and postmenopausal patients (P < 0.001) in the metformin and non-metformin groups than in the nondiabetic group. Moreover, the probability of having cardiovascular and cerebrovascular disease was also higher (P < 0.001) in the metformin and non-metformin groups. For the Luminal B (high ki67) and Luminal B (her-2/neu +) subgroups, there was a higher proportion of obese patients in the metformin and non-metformin groups (P < 0.001). In terms of clinical characteristics, for the Luminal B (high ki67) subtype, the proportion of patients with invasive ductal carcinoma was lower in the non-metformin group than in the other two groups (P = 0.001). In both the metformin and non-metformin groups, the proportion of T3/4 patients was higher (P < 0.001), the proportion of patients with lymph node metastasis was higher (P = 0.001), and the proportion of patients with vessel carcinoma embolus was higher (P = 0.001) compared with the nondiabetic group. In conclusion, compared with the metformin group, the non-metformin group had a poorer prognosis for all subtypes of luminal breast cancer. In the diabetic group, only patients with the Luminal B (high ki67) subtype exhibited a poorer prognosis. Therefore, different diabetes medication may have a different impact on the prognosis of different subtypes of luminal breast cancer. © 2013 International Society of Oncology and BioMarkers (ISOBM).


Hou G.,Tianjin Medical University | Hou G.,Key Laboratory of Breast Cancer Prevention and Therapy | Hou G.,Key Laboratory of Cancer Prevention and Therapy | Zhang S.,Tianjin Medical University | And 14 more authors.
Breast Cancer Research and Treatment | Year: 2013

The purpose of this study was to investigate the clinical, pathological, and prognostic characteristics of breast cancer patients with diabetes. In total, the study included 1,013 breast cancer patients with diabetes and 4,621 breast cancer patients without diabetes. Patients with diabetes were further divided into the metformin- and nonmetformin-treated subgroups. The percentage of elderly patients (P < 0.001), obese patients (P < 0.001), and menopausal patients (P < 0.001) as well as the percentage of patients with cardio-cerebrovascular complications (P < 0.001), negative PR (P < 0.001) expression, or low Ki67 expression (P = 0.001) tended to be higher in the diabetic group. In addition, these patients had later pathological stages (P < 0.001), more lymph node metastasis (P = 0.014), and a lower percentage of them were on the anthracycline-based chemotherapy regimen (P = 0.003). The diabetic group was further divided into the metformin and nonmetformin-treated subgroups. The pairwise comparison between the metformin-treated subgroup and the control group did not show a significant difference in the pathological stages (P = 0.0079). However, the HER-2 positive rate tended to be lower in the metformin-treated subgroup than in the nonmetformin-treated subgroup (P = 0.002). No significant difference was found in the lymph node status between the nonmetformin-treated subgroup and the control group (P = 0.057), while the nonmetformin-treated subgroup was associated with higher HER-2 positive expression (P = 0.002). The median follow-up time for this study was 68 months (10-120 months). In Kaplan-Meier analysis, The diabetic group predicted worse survival compared with the control group (P < 0.001) with 5-year survival rates of 79 and 82 %, respectively. The breast cancer mortality rates in the metformin-treated subgroup, the nonmetformin-treated subgroup, and the control group were significantly different (long-rank test, P < 0.001), and the 5-year survival rates were 88, 73, and 82 %, respectively. As shown in the multivariate survival analysis using Cox's regression model, compared with the control group, the metformin-treated subgroup was associated with lower mortality risk (HR 0.762; 95 % CI 0.6-0.968; P = 0.026), whereas the nonmetformin-treated subgroup was associated with higher mortality risk (HR 1.708; 95 % CI 1.461-1.997; P < 0.001). In conclusion, the diabetic group is associated with poor prognosis. Compared with the control group, the metformin-treated subgroup is associated with better clinical outcomes, while nonmetformin-treated subgroup with poorer prognosis. The selection of different antidiabetic drugs may impact the prognosis of breast cancer patients with diabetes. © 2013 Springer Science+Business Media New York.


Ma T.,Tianjin Medical University | Ma T.,Key Laboratory of Breast Cancer Prevention and Therapy | Ma T.,Key Laboratory of Cancer Prevention and Therapy | Yang L.,Tianjin Medical University | And 5 more authors.
Oncology Reports | Year: 2015

Trastuzumab (Herceptin) has been widely used in breast cancer treatment. However, the majority of cancers that initially respond to trastuzumab begin to progress again within 1 year. Despite the high resistance rate, the molecular mechanisms underlying this desease are not well understood. In the present study, microRNA (miRNA-542-3p modulated trastuzumab resistance in SKBR3 and MCF7/Her2 breast cancer cell lines. Trastuzumab induced miRNA-542-3p expression in SKBR3 and MCF7/Her2 cells. Furthermore, knockdown of miRNA-542-3p in the two cell lines resulted in decreased drug sensitivity to trastuzumab and cell apoptosis. The blockage of G1/S checkpoint by trastuzumab was rescued as well-miRNA-542-3p knockdown also activated the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, while LY294002 reversed the effect of miRNA-542-3p knockdown. In summary, the results suggested that miRNA-542-3p downregulation may contribute to the trastuzumab resistance in breast cancer via, at least in part, the PI3K-akt pathway. Our findings provide new molecular mechanisms in trastuzumab resistance.


Zhu Y.,Tianjin Medical University | Zhu Y.,Key Laboratory of Breast Cancer Prevention and Therapy | Zhu Y.,Key Laboratory of Cancer Prevention and Therapy | Zhang X.,Tianjin Medical University | And 17 more authors.
Tumor Biology | Year: 2012

This study evaluated the effects of a mammalian target of mTOR inhibitor everolimus alone or in combination with trastuzumab on stem cells from HER2-overexpressing primary breast cancer cells and the BT474 breast cancer cell line in vitro and in vivo. For the in vitro studies, we sorted ESA +CD44+CD24-/low cells as stem cells from primary breast cancer cells and BT474 cells using flow cytometry. The MTT assay was used to quantify the inhibitory effect of the drugs on total cells and stem cells specifically. Stem cell apoptosis, cell cycle distributions, and their tumorigenicity after treatment were investigated by flow cytometry or soft agar colony formation assays. For the in vivo studies, BALB/c mice were injected with BT474 stem cells, and the different treatments were administered. After necropsy, the expression of Ki67, CD31, AKT1, and phospho-AKT (Thr308) was analyzed by immunohistochemistry. For the in vitro studies, Treatment with everolimus resulted in stem cell growth inhibition in a dose-dependent manner. The combination of everolimus with trastuzumab was more effective at inhibiting cell growth (P < 0.001) and tumorigenicity (P < 0.001) compared with single-agent therapy. In addition, an increase in G1 cell cycle arrest and an increased population of cells in early apoptosis were seen in the combination treatment group compared with either of the single-agent groups (P < 0.01). For the in vivo studies, everolimus plus trastuzumab therapy was much more effective at reducing tumor volume in mice compared with either single agent alone (P < 0.05). Compared with everolimus alone, the combination of everolimus and trastuzumab reduced the expression of Ki67, AKT1, and phospho-AKT (Thr308) (P < 0.05). We conclude that everolimus has effective inhibitory effects on HER2-overexpressing stem cells in vitro and vivo. Everolimus plus trastuzumab is a rational combination treatment that may be promising in human clinical trials. © 2012 International Society of Oncology and BioMarkers (ISOBM).


Sun B.,Tianjin Medical University | Hou G.,Tianjin Medical University | Hou G.,Key Laboratory of Breast Cancer Prevention and Therapy | Zhang X.,Tianjin Medical University | And 5 more authors.
Chinese Journal of Clinical Oncology | Year: 2013

Objective: To investigate the clinical, pathological, and prognostic characteristics of luminal B breast cancer patients with diabetes. Methods: A total of 479 luminal B breast cancer patients with diabetes and 3 392 luminal B breast cancer patients without diabetes who were treated between January 2002 and December 2006 were enrolled in this study. The luminal B breast cancer patients were further divided into the luminal B (high ki67) and luminal B (Her-2/neu+) subgroups. Each subgroup was further grouped into metformin-treated, non-metformin-treated, and non-diabetic groups. The indicators included cancer-specific mortality, clinical, pathological stage, lymph node status, chemotherapy, and endocrine therapy. The survival analysis of each group was performed using the Kaplan-Meier method, and the significance was determined using the logrank test. Cox proportional hazard model was used to examine the correlation between each factor and the prognosis. Results: The Kaplan-Meier analysis results revealed that the breast cancer mortality rates in the metformin-treated, non-metformin-treated, and non-diabetic groups were significantly different in both luminal B (high ki67) and luminal B (Her-2/neu+) subgroups (logrank test: P<0.001, P=0.035), and the respective five-year survival rates were 93.5%, 81%, and 89% for the luminal B (high ki67) subgroup and 84%, 77%, and 83% for the luminal B (Her-2/neu+) subgroup. The Cox multifactorial regression analysis results showed that compared with the metformin-treated group, the non-metformin-treated group was associated with a significantly increased risk of mortality (P<0.001, P=0.044) in the two subgroups. Meanwhile, the non-diabetic group was associated with an increased risk of mortality (P=0.038) in the luminal B (high ki67) subgroup only. The percentage of elderly (P<0.00\), menopausal (P<0.001), obese (P<0.001), and patients with cardio-cerebrovascular complications (P<0.001) tended to be higher in the metformin-treated and non-metformin-treated groups than in the diabetic group. Moreover, the metformin- and non-metformin-treated groups in the luminal B (high ki67) subgroup were associated with high percentages of T 3/4 pathological stage (P<0.001), lymph node metastasis (P=0.001). The non-metformin-treated group was associated with a lower percentage of invasive ductal carcinoma (P=0.001) compared with the other two groups. Conclusion: The non-metformin-treated group resulted in worse clinical outcomes in both subgroups compared with the metformin-treated group. Meanwhile, the non-diabetic group resulted in the worst prognosis among the three groups in the luminal B (high ki67) subgroup. These findings suggest that the choice of different anti-diabetic drugs may influence the prognosis of luminal B breast cancer patients with diabetes.


Li Y.,Tianjin Medical University | Wu J.,Tianjin Medical University | Zhang W.,Tianjin Medical University | Zhang N.,Tianjin Medical University | And 3 more authors.
British Journal of Cancer | Year: 2013

Background:Early serum detection is of critical importance to improve the therapy for hepatocellular carcinoma (HCC), one of the most deadly cancers. Hepatitis infection is a leading cause of HCC.Methods:In the present study, we collected total serum samples with informed consent from 80 HCC patients with HBV (+)/cirrhosis (+), 80 patients with benign diseases (50 liver cirrhosis patients and 30 HBV-infected patients) and 60 healthy controls. Analysis was by using surface-enhanced laser desorption/ionisation-time-of-flight mass spectroscopy (SELDI-TOF-MS) to find new serum markers of HCC. SELDI peaks were isolated by SDS-PAGE, identified by LC-MS/MS and validated by immunohistochemistry (IHC) in liver tissues. Migration and invasion assay were performed to test the ability of cell migration and invasion in vitro.Results:SELDI-TOF-MS revealed a band at 7777 M/Z in the serum samples from HCC patients but not from healthy controls or patients with benign diseases. The protein (7777.27 M/Z) in the proteomic signature was identified as C-C motif chemokine 15 (CCL15) by peptide mass fingerprinting. A significant increase in serum CCL15 was detected in HCC patients. Functional analysis showed that HCC cell expressed CCL15, which in turn promoted HCC cell migration and invasion.Conclusion:CCL15 may be a specific proteomic biomarker of HCC, which has an important role in tumorigenesis and tumour invasion. © 2013 Cancer Research UK. All rights reserved.


Ding T.,Key Laboratory of Breast Cancer Prevention and Therapy | Gu F.,Key Laboratory of Breast Cancer Prevention and Therapy | Fu L.,Key Laboratory of Breast Cancer Prevention and Therapy | Ma Y.-J.,Tianjin Medical University
Journal of Clinical Neuroscience | Year: 2010

Aquaporin-4 (AQP4) is the most important member of the aquaporin (AQP) family in the central nervous system and has a key role in maintaining water and ion homeostasis. It is clear that AQP4 participates in brain edema after injury and other brain diseases. Various studies report that AQP4 is significantly up-regulated in glioblastoma multiforme compared to low-grade glioma and normal brain tissue, suggesting that it might be involved in tumor malignancy as well as regulation of brain edema. Recent discoveries of AQP4 involvement in cell migration and cytoskeleton organization suggest that AQP4 has a critical role in glioma malignancy. This review focuses on the newly discovered functions and molecular mechanisms of AQP4 in infiltrative gliomas. © 2010 Elsevier Ltd. All rights reserved.

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