Heilongjiang Institute for Cancer Research

Harbin, China

Heilongjiang Institute for Cancer Research

Harbin, China
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Song Y.,Harbin Medical University | Liu X.,Harbin Medical University | Liu X.,Lovelace Medical Center | Zhang G.,Harbin Medical University | And 12 more authors.
World Journal of Surgical Oncology | Year: 2013

Background: Metaplastic breast carcinoma is a rare aggressive malignant neoplasm. The purposes of this study are to review the pathologic features and clinical outcomes of metaplastic breast carcinoma compared to invasive ductal carcinoma and to evaluate the prognosis of metaplastic breast carcinoma. Methods: The cases of 55 patients with metaplastic breast carcinomapresenting between 1991 and 2006 were analyzed and compared to the cases of 767 age-matched patients with invasive ductal carcinoma from the same time period.Results: The group of patients with metaplastic breast carcinoma presented with a larger tumor size, lower lymph node involvement, higher percentage of triple-negative (estrogen receptor-, progesterone receptor- and human epidermal growth factor receptor-2-negative) cases, and Ki-67 over-expression compared with the group of patients with invasive ductal carcinoma and triple-negative invasive ductal carcinomas. Patients in the metaplastic breast carcinoma group tended to have more local (often chest wall) recurrences (P = 0.038) and distant (often lung) metastases (P = 0.001) than those in the invasive ductal carcinomas group. The prognosis of metaplastic breast carcinoma was poorer than that of invasive ductal carcinoma and triple-negative invasive ductal carcinomas; the 5-year overall survival rate was 54.5% in metaplastic breast carcinoma versus 85.1% in invasive ductal carcinoma, and 73.3% in triple-negative invasive ductal carcinomas (P <0.001). The 5-year disease-free survival rate was 45.5% in metaplastic breast carcinoma versus 71.2% in invasive ductal carcinoma, and 60.3% in triple-negative invasive ductal carcinomas (P <0.001). Multivariate analysis revealed tumor size larger than 5.0 cm, lymph node involvement and Ki-67≥14% were significantly related to 5-year overall survival (P = 0.010; P = 0.010; P = 0.035) and 5-year disease-free survival (P = 0.020; P = 0.018; P = 0.049).Conclusions: Metaplastic breast carcinoma shows a poorer prognosis than both invasive ductal carcinoma and triple-negative invasive ductal carcinomas. Tumor size larger than 5.0 cm, lymph node involvement and Ki-67 ≥14% indicate a poor prognosis in patients with metaplastic breast carcinoma. © 2013 Song et al.; licensee BioMed Central Ltd.


Zhang X.,Harbin Medical University | Sun Q.,Harbin Medical University | Shan M.,Harbin Medical University | Niu M.,Harbin Medical University | And 16 more authors.
PLoS ONE | Year: 2013

ARID1A (AT-rich interactive domain 1A) has recently been identified as a tumor suppressor gene. Its mRNA expression is significantly low in many breast cancers; this is often associated with more aggressive phenotypes. However, the underlying molecular mechanism for its low expression has not been fully understood. This study was undertaken to evaluate the contribution of gene copy number variation, mutations, promoter methylation and histone modification to ARID1A's low expression. 38 pairs of breast invasive ductal carcinomas and their normal breast tissue counterparts from the same patients were randomly selected for gene expression and copy number variation detection. Promoter methylation and histone modification levels were evaluated by MeDIP-qPCR and ChIP-qPCR, respectively. PCR product Sanger sequencing was carried out to detect the exon mutation rate. Twenty-two out of 38 invasive ductal carcinomas in the study (57.9%) revealed ARID1A mRNA low expression by realtime RT-PCR. The relative promoter methylation level was, significantly higher in ARID1A mRNA low expression group compared with its high expression group (p<0.001). In the low expression group, nineteen out of 22 invasive ductal carcinomas (86.4%) exhibited ARID1A promoter hypermthylation. In addition, the promoter hypermethylation was accompanied with repressive histone modification (H3K27Me3). Although five out of 38 invasive ductal carcinomas (13.2%) exhibited loss of ARID1A gene copy number by realtime PCR and nine exon novel mutations are seen from eight out of 33 invasive ductal carcinomas (24.2%), there was no statistically significant difference in both ARID1A mRNA low and high expression groups (p = 0.25,and p = 0.68, respectively). We demonstrate that promoter hypermethylation was the main culprit for ARID1A mRNA low expression in invasive ductal carcinomas. The influence of mutation and copy number variation on the expression were statistically insignificant at mRNA level, and were, therefore, not considered the main causes for ARID1A mRNA low expression in invasive breast cancer. © 2013 Zhang et al.


Song Y.-N.,Harbin Medical University | Geng J.-S.,Harbin Medical University | Liu T.,Harbin Medical University | Zhong Z.-B.,Harbin Medical University | And 9 more authors.
PLoS ONE | Year: 2012

Background: The androgen receptor (AR) expression and the CAG repeat length within the AR gene appear to be involved in the carcinogenesis of male breast carcinoma (MBC). Although phenotypic differences have been observed between MBC and normal control group in AR gene, there is lack of correlation analysis between AR expression and CAG repeat length in MBC. The purpose of the study was to investigate the prognostic value of CAG repeat lengths and AR protein expression. Methods: 81 tumor tissues were used for immunostaining for AR expression and CAG repeat length determination and 80 normal controls were analyzed with CAG repeat length in AR gene. The CAG repeat length and AR expression were analyzed in relation to clinicopathological factors and prognostic indicators. Results: AR gene in many MBCs has long CAG repeat sequence compared with that in control group (P = 0.001) and controls are more likely to exhibit short CAG repeat sequence than MBCs. There was statistically significant difference in long CAG repeat sequence between AR status for MBC patients (P = 0.004). The presence of long CAG repeat sequence and AR-positive expression were associated with shorter survival of MBC patients (CAG repeat: P = 0.050 for 5y-OS; P = 0.035 for 5y-DFS AR status: P = 0.048 for 5y-OS; P = 0.029 for 5y-DFS, respectively). Conclusion: The CAG repeat length within the AR gene might be one useful molecular biomarker to identify males at increased risk of breast cancer development. The presence of long CAG repeat sequence and AR protein expression were in relation to survival of MBC patients. The CAG repeat length and AR expression were two independent prognostic indicators in MBC patients. © 2012 Song et al.


Sun S.,Harbin Medical University | Jiang Y.,Harbin Medical University | Zhang G.,Harbin Medical University | Song H.,Harbin Medical University | And 6 more authors.
Journal of Surgical Oncology | Year: 2012

Background and objectives Although there is growing evidence supporting the hypothesis that fibroblast growth factor receptor 2 (FGFR2) is one of the few candidate genes linked with breast cancer susceptibility, the precise role of FGFR2 protein expression in breast cancer is still unknown. Our study examines FGFR2 protein expression in breast cancer and determines its associations with clinicopathological features and survival. Methods Specimens from 125 invasive ductal carcinoma grade 2 (IDC2) breast cancer patients were investigated by immunohistochemistry for FGFR2 protein expression. Associations between the expression of FGFR2 and various clinicopathological features as well as survival status were studied. Result Cytoplasmic and nuclear FGFR2 were expressed in 64.8% and 56.8% of breast cancer patients, respectively. Cytoplasmic FGFR2 expression was significantly associated with tumor size and TNM stage. Furthermore, patients with high expression levels of cytoplasmic and nuclear FGFR2 showed much lower overall survival (OS) and disease-free survival (DFS) rates than those patients with low FGFR2 expression. Cytoplasmic FGFR2 expression and lymph node metastasis were independent prognostic factors for both DFS and OS by multivariate analysis. Conclusions High FGFR2 expression is correlated with poor OS and DFS in breast cancer patients. It could be a biomarker for poor prognosis. Copyright © 2011 Wiley Periodicals, Inc.


Lv Z.,Harbin Medical University | Lv Z.,Heilongjiang Institute for Cancer Research | Yang L.,Harbin Medical University | Yang L.,Heilongjiang Institute for Cancer Research
Molecular Medicine Reports | Year: 2013

Glioblastoma multiforme (GBM) is a lethal brain tumor in adults. Despite advances in treatments, such as surgery, radiotherapy and chemotherapy, high-grade glioma remains fatal. The molecular and cellular mechanisms for GBM are not entirely clear and further studies are required to elucidate these. MicroRNAs (miRNAs) are small, non-coding, endogenous RNAs that are involved in cell differentiation and proliferation, and have been suggested to play a role in a variety of types of cancer. In this study, we investigated the role of miR-124 in the inhibition of proliferation of GBM cells. The downregulation of miR-124 in human GBM tumor cell lines was detected using quantitative RT-PCR. To assess the function of miR-124, we constructed stable cell lines, U87-124 and U373-124, which overexpressed miR-124 using lentiviral vectors. Overexpression of miR-124 inhibited the proliferation of GBM cancer cells in vitro. Using integrated bioinformatics analysis, SOS1 was found to be a direct target for miR-124, which is frequently upregulated in gliomas. Dual-luciferase reporter assays confirmed that the SOS1 mRNA 3'-untranslated regions (UTR) was directly targeted by miR-124 and that the mutated 3'UTR was not affected. This was revealed to be mechanistically associated with the induction of SOS/Ras/Raf/ERK and the suppression of ERK activity, which was achieved by silencing SOS1. This study therefore indicates an important role for miR-124 in the regulation of growth in the molecular etiology of GBM, and offers a potential strategy for the use of miR-124 in cancer treatment.


Zhang X.,Harbin Medical University | Zhang Y.,Harbin Medical University | Yang Y.,Heilongjiang Institute for Cancer Research | Niu M.,Harbin Medical University | And 9 more authors.
Cancer Epidemiology | Year: 2012

Background: ARID1A gene encodes BAF250a which is a member of the ARID family of DNA-binding proteins and a subunit of human SWI/SNF-related complexes. Low expression of ARID1A has been correlated with specific tumor cell lines or specific pathological types of cancer tissue. The purpose of this study was to investigate the expression of ARID1A in invasive ductal breast carcinomas and to evaluate its clinicopathological characteristics and prognostic value. Methods: ARID1A mRNA expression was evaluated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 40 pairs of fresh frozen breast cancer and normal breast samples. BAF250a expression was evaluated by immunohistochemistry in 112 paraffin-embedded surgical specimens of invasive breast cancers and 20 cases of matched normal breast tissues. We further analyzed the clinicopathological characteristics of ARID1A expression. Overall survival time was assessed by the Kaplan-Meier method and Cox regression model. Results: ARID1A mRNA expression was lower in breast cancer tissue than in corresponding normal tissue (P< 0.001), and this decreased expression level was markedly associated with factors such as larger tumor size (P= 0.038), higher stage (P= 0.016), ER(-) (P= 0.038), higher Ki-67 (P= 0.025), P53 mutation (P= 0.018) and ER(-)/PR(-)/Her-2(-) molecular subtype (P= 0.044). With immunohistochemical staining, we showed that low BAF250a expression existed in 56% (63/112) of the breast cancers tissues. Low BAF250a expression was significantly associated with tumor stage (P= 0.021), P53 (P= 0.018), Ki-67 (P= 0.031) and ER(-)/PR(-)/Her-2(-) molecular subtype (P= 0.044). Low ARID1A expression was a predictor, not an independent, of overall survival. Conclusion: These data suggest that low ARID1A expression is frequent in breast cancers, and we need to investigate further the role of ARID1A and SWI/SNF complexes in breast tumorigenesis, especially in triple-negative breast cancer. © 2011 .


Liu T.,Harbin Medical University | Ye L.,Harbin Medical University | Guan X.,Harbin Medical University | Liang X.,Harbin Medical University | And 7 more authors.
International Journal of Biological Macromolecules | Year: 2013

One water-soluble polysaccharide (PCPw) was isolated and purified from the roots of Pulsatilla chinensis by DEAE cellulose-52 and Sephadex G-100 column chromatography, and its antitumor activity was evaluated on 4T1 tumor-bearing mice through transplantable animal tumor. After 10 days of PCPw (50, 100 and 200. mg/kg) treatment once daily in tumor-bearing mice, PCPw oral administration could not only significantly inhibit the growth of transplantable 4T1 tumor in mice but also promote concanavalin A (Con A), lipopolysaccharide (LPS)-stimulated splenocytes proliferation, the serum lysozyme level and 2,4-dinitrofluorobenzene (DNFB)-induced delayed-type hypersensitivity (DTH) reactions, especially at the dose of 100. mg/kg. Meanwhile, significant improvements in peripheral blood abnormality and anemia were observed in PCPw-treated group. These results suggested that PCPw could improve both cellular and humoral immune response and might be explored as a potential natural antitumor drug. © 2012 Elsevier B.V.


Liu T.,Harbin Medical University | Zhang X.,Harbin Medical University | Shang M.,Harbin Medical University | Zhang Y.,Harbin Medical University | And 5 more authors.
Journal of Surgical Oncology | Year: 2013

Background: Among the different types of breast cancer, basal-like breast cancer (BLBC) has an extremely poor prognosis due to its high rate of recurrence and metastasis. The present study aimed to investigate the correlation between the expression of Slug, E-cadherin, and vimentin, and the clinicopathological characteristics and prognosis of patients with BLBC. We further inferred from these findings whether Slug leads to a poor prognosis in patients with BLBC through epithelial-mesenchymal transition (EMT). Methods: Immunohistochemistry was performed for 441 patients with breast cancer to determine the expression levels of Slug, E-cadherin, and vimentin. The correlation between protein expression and clinicopathological characteristics of patients with BLBC was evaluated, and these patients were followed up to determine survival rate. Results: High Slug and low E-cadherin expression in BLBC patients closely correlated with histological grade, lymph node metastasis, tumor-node-metastasis (TNM) stage, and lymphatic vessel metastasis. Survival analysis revealed that the poor prognosis of BLBC is associated with TNM stage, high Slug and vimentin expression, and low E-cadherin levels. Conclusions: High Slug expression is closely correlated with poor prognosis in patients with BLBC. We speculate that this may be attributed to the involvement of Slug in the EMT of BLBC. © 2012 Wiley Periodicals, Inc.

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