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ABSTRACT: Abstract Purpose: The aim of this study was to investigate the relationship between the expressions of microRNA-9 (miR-9) and microRNA-200c (miR-200c) in human breast cancers and clinicopathological features. Methods: We investigated the expressions of miR-9 and miR-200c in 68 patients with breast cancers using the quantitative reverse transcription-polymerase chain reaction method, and assessed the E-cadherin status using the immunohistochemistry method. Results: The relative expression levels of miR-9 and miR-200c in breast cancer patients with lymph node metastasis were higher than that of patients without lymph node metastasis. The expression of miR-9 correlated inversely with E-cadherin expression. Conclusions: The results showed that higher expressions of miR-9 and miR-200c in human breast cancers were associated with lymph node metastasis. This study indicated that the elevation of miR-9 and miR-200c in human breast cancers can induce an invasive phenotype and may serve as a molecular diagnostic marker for patients with breast cancer.
Cancer Biotherapy & Radiopharmaceuticals 04/2013; · 1.44 Impact Factor
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ABSTRACT: BACKGROUND: Inhibitor of growth 4 (ING4) has deserved attention as a tumor suppressor gene in many malignant tumors. In our study, we investigated ING4 immunoexpression in gastrointestinal stromal tumors (GISTs) and its prognostic value. METHOD: The expression of ING4 and Ki67 was investigated in 41 samples of various risk gastrointestinal stromal tumors by immunohistochemical technique. The associations of ING4 expression and clinicopathological parameters, and prognosis of the patients, were analyzed by multivariate Cox regression analysis. RESULTS: ING4 expression showed a decreased trend from lower-risk to high-risk gastrointestinal stromal tumors, and an opposite trend for Ki67 expression. In lower-risk tumors, it was found the expression level of ING4 was 78.95 % ± 27.90 % and that of Ki67 was 4.42 % ± 3.75 %. However, in high-risk tumors, the expression level of ING4 was 9.23 % ± 7.66 % and that of Ki67 was 18.50 % ± 9.09 %. There was a strongly negative correlation between the expression levels of ING4 and Ki67. A significant difference was observed in the expression of ING4 between invasion and non-invasion (p < 0.001). The expression of ING4 was markedly correlated with tumor size (p < 0.001), mitotic index (p < 0.001), tumor necrosis (p = 0.021), invasion (p < 0.001), recurrence and metastasis (p = 0.021), and mortality (p < 0.001). CONCLUSION: The low expression level of ING4 protein was correlated with high-risk GISTs. ING4 might be involved in the progression of GISTs and inhibit its invasion. ING4 might be one of the prognostic indicators in GISTs.
Gastric Cancer 03/2013; · 2.42 Impact Factor
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ABSTRACT: We aimed to investigate risk factors of local and distant recurrence in small-sized, node negative breast cancer in women <35 years in a Chinese cohort. Between January 1994 and January 2007, 107 patients with pathologically confirmed small-sized ([Symbol: see text]1 cm), node negative breast cancer who did not receive neoadjuvant or adjuvant chemotherapy were included. The 5-year recurrence-free survival (RFS) was estimated according to different prognostic variables. With a median time of 60 months (range, 8-60 months) follow-up, local and distant recurrence were observed in 25 cases (23.4%). By univariate analysis, HER-2 positivity, triple negative (TN), and high Ki-67 index ([Symbol: see text] 14%) were risk factors of a lower RFS (hazard ratio (HR) 6.680, 95% confidence interval (CI) 2.350-18.985, P<0.0001 for HER-2 positive; HR 4.769, 95%CI 1.559-14.591, P=0.006 for TN; HR 6.030, 95%CI 2.659-13.674, P<0.0001 for high Ki-67 index). Patients with grade 3 tumors had a lower RFS (HR 2.922, 95%CI 1.096-7.791, P=0.032) compared with those with grade 1 or grade 2 tumors. By multivariate analysis, HER-2 positivity (HR 10.204, 95%CI 3.391-30.704, P<0.0001), TN (HR 10.521, 95% CI 3.152-35.113, P<0.0001) and high Ki-67 index (HR 10.820, 95%CI 4.338-27.002, P<0.0001) remained risk factors of RFS. In this cohort, HER-2 positivity, triple negative and high Ki-67 index were independent risk factors of RFS in young patients with T1a,bN0 breast cancer. Subsequent pregnancy did not affect RFS.
Science China. Life sciences 03/2013; · 2.02 Impact Factor
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ABSTRACT: Microtubule-associated protein 1 light chain 3B (LC3B) was involved in autophagosome formation and had been as a marker of autophagy which played an important role in the development of breast cancer. The purpose of this study was to explore the level of LC3B expression in four stages of triple-negative breast cancer (TNBC) and to evaluate the prognostic significance of LC3B expression in TNBC. The ultimate aim was to identify the new factor that could be useful in predicting clinical behavior of TNBC. We evaluated the expression level of LC3B protein in four kinds of TNBC tissue samples, including intraductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) without metastases, IDC with lymph node metastases (LNM), and IDC with distant metastases (DM). Hundred and four primary TNBC patients were involved in present study, and the expression level of LC3B protein was assessed by immunohistochemistry. Medical records of these patients were reviewed, and the clinicopathological analysis was performed. High expression of LC3B was observed in 7.7 % of DCIS (1 of 13 cases), 16.2 % of IDC (6 of 37 cases), 35.7 % of LNM (15 of 42 cases), and 58.3 % of DM (7 of 12 cases). LC3B high expression was significantly associated with tumor size (P = 0.028), lymph node metastasis (P = 0.002), and Ki-67 expression (P = 0.047). LC3B high expression patients showed poorer DFS and OS rates compared with LC3B low expression patients (P = 0.024, and P = 0.047, respectively). Multivariate analyses confirmed that high LC3B expression was an independent and significant factor for predicting the poor outcome of TNBC patients. These preliminary results demonstrated that high LC3B expression was associated with lymph node and distant metastasis. Furthermore, high LC3B protein expression was correlated with shorter survival in patients with triple-negative breast carcinoma. These findings provided preliminary evidence for the function of LC3B on the progression of TNBC and suggested LC3B was a useful marker in prognostic evaluation for patients with TNBC.
Medical Oncology 03/2013; 30(1):475. · 2.14 Impact Factor
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Shu Zhao,
Wenjie Ma,
Minghui Zhang,
Dabei Tang,
Qingtao Shi,
Shanqi Xu,
Xiaosan Zhang,
Yupeng Liu,
Ying Song,
Leyuan Liu, Qingyuan Zhang
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ABSTRACT: The aim of this study was to investigate expression of CD147 and MMP-9 in triple-negative breast cancer (TNBC) so as to determine whether these two proteins may be correlated with poor prognosis of TNBC patients. We examined the expression levels of the CD147 and MMP-9 in 127 patients with TNBC and 30 patients with mammary gland fibroma using immunohistochemical staining before any treatments. Furthermore, we analyzed the correlation between the expression of these two proteins and various clinicopathologic factors including survival status of patients with TNBC. Positive stain of CD147 and MMP-9 was observed in all samples of TNBC. A statistically positive correlation was observed between the expression levels of CD147 and MMP-9 in TNBC tissues. The incidences of high expression were 48.0 % for CD147 and 53.5 % for MMP-9 in 127 TNBC tissues, respectively. High expression of either CD147 or MMP-9 was significantly correlated with clinical feature and shorter progression-free survival (PFS) (P(CD147) = 0.039; P(MMP-9) = 0.017) and overall survival (OS) (P(CD147) = 0.037; P(MMP-9) = 0.023). The expression levels of CD147 and MMP-9 are positively correlated with invasion, metastasis and shorter PFS/OS of TNBC. Patients with high expression of CD147 and MMP-9 had poor prognosis than TNBC patients with low expression.
Medical Oncology 03/2013; 30(1):335. · 2.14 Impact Factor
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Dabei Tang, Qingyuan Zhang,
Shu Zhao,
Jincai Wang,
Kangping Lu,
Ying Song,
Ling Zhao,
Xinmei Kang,
Jingxuan Wang,
Shanqi Xu,
Lantian Tian
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ABSTRACT: OBJECTIVES: To investigate the expression profile of miR-1258 and heparanase (HPSE) in breast cancer and to assess their clinicopathological significance. DESIGN AND METHODS: The expression levels of miR-1258 and HPSE were analyzed in normal, benign and malignant breast tissues. Their serum levels were evaluated in healthy women and in patients with benign and malignant breast disease. We studied the correlation between the expression of miR-1258 and HPSE and the clinical features presented by the patients. RESULTS: MiR-1258 was down-regulated and HPSE was up-regulated in breast cancer, with a significant inverse correlation. A reduced miR-1258 expression and an elevated HPSE expression were associated with the lymph node status, late clinical stages, a short overall survival and a short relapse-free survival. In frozen fresh tissue samples, the miR-1258 levels in breast cancer with lymph node metastasis were significantly lower than that of breast cancer without lymph node metastasis and benign disease (BD). In contrast, the HPSE levels in breast cancer with lymph node metastasis were the highest. In serum samples, the miR-1258 levels in metastatic breast cancer (M1) were lower than that of primary breast cancer (M0) and BD. However, serum HPSE levels of M1 patients were significantly higher than that of M0 patients and BD patients. CONCLUSIONS: MiR-1258 may play an important role in breast cancer development and progression by regulating the expression of HPSE, and they might be potential prognostic biomarkers for breast cancer.
Clinical biochemistry 02/2013; · 2.02 Impact Factor
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ABSTRACT: Choroidal melanoma is the most common intraocular malignancy and can be fatal in half of the patients because of metastatic disease. Metastasis of choroidal melanoma to the omentum is extremely rare and, to our knowledge, no such case has ever been described in the literature. Here we present a 41-year-old Chinese man with an omental metastasis, 5 years after he was diagnosed with a spindle-cell-type malignant melanoma of the choroid and had his left eye enucleated. The patient demonstrated some uncommon symptoms, but the diagnosis was confirmed histopathologically. The cells were positive for S-100, HMB-45 and Melan-A proteins. He underwent a complete tumor resection and concomitantly received chemotherapy, biological treatment and traditional Chinese medicine. At 2-year follow-up, this patient continues to do well.
Japanese Journal of Clinical Oncology 01/2013; · 1.78 Impact Factor
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Zhongcheng Shi,
Zhenyu Cai,
Jingcui Yu,
Tingting Zhang,
Shu Zhao,
Emanuel Smeds, Qingyuan Zhang,
Fen Wang,
Changhong Zhao,
Songbin Fu,
Sankar Ghosh,
Dekai Zhang
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ABSTRACT: Toll-like receptors (TLRs) are key molecular sensors used by the mammalian innate immune system to detect microorganisms. Although TLR functions in colonic immune homeostasis and tolerance to commensal bacteria have been intensively researched, the precise roles of different TLRs in response to pathogen infection in the gut remain elusive. Peyer patches are the major entrance of Salmonella infection and antigen transportation in intestine. Here, we report that, in contrast to TLR5 as a carrier of Salmonella, TLR11 works as a blocker of Salmonella to prevent highly invasive Salmonella from penetrating into the murine Peyer patches and spreading systemically. TLR11 plays an important role in mediating TNF-alpha induction and systemic inflammation in response to Salmonella infection. Remarkably, mice lacking TLR11 are induced apparent hemorrhage at Peyer patches by highly invasive Salmonella, a phenotype resembling human Salmonella infection. Therefore, our results indicate a potentially important role for TLR11 in preventing murine intestinal infection and modulating antigen transportation in the gut and imply an important role for various TLRs in cooperation to tightly control of pathogens penetrating into Peyer patches. TLR11 knockout mouse can serve as a good animal model to study Salmonella infection.
Journal of Biological Chemistry 11/2012; · 4.77 Impact Factor
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Shu Zhao,
Huike Yang,
Minghui Zhang,
Dekai Zhang,
Yupeng Liu,
Yan Liu,
Ying Song,
Xiaosan Zhang,
Hongbin Li,
Wenjie Ma, Qingyuan Zhang
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ABSTRACT: In order to investigate the prognostic value of circulating tumor cells (CTCs) in patients with metastatic breast cancer (MBC), the blood cells from 98 MBC patients and 60 controls were evaluated by RT-PCR to detect the presence of markers EpCAM, CK19, and hMAM. Peripheral blood was obtained from all patients with MBC before any systemic therapy. Immunofluorescence staining experiment was conducted on CTCs samples from 10 patients to investigate the coexpression of EpCAM, CK19, and hMAM. In addition, analyses were carried out for their correlation with patients' clinicopathologic features. EpCAM+, CK19+, and hMAM+ cells were detected in 50 (51.0 %), 43 (43.9 %), and 68 (69.4 %) of the 98 patients, respectively. Triple-marker-positive CTCs were detected in 86 of 98 (87.8 %) patients with a significantly higher rate than the control group. Among the 98 patients, 12 (12.2 %) patients were negative for three genes, 34 (34.7 %) positive for one gene, 29 (29.6 %) positive for any two genes, and 23 (23.5 %) positive for all three genes. Compared to single-marker detection, the triple combined marker detection exhibited significantly higher rate. Furthermore, the specificity of triple combined markers of serial test was 100 %. The expression of three genes was significantly correlated with lymph node metastasis, high histological grade, and high levels of serum CA153 and CEA. Double-immunofluorescence labeling confirmed the presence of following CTCs phenotypes: CK19+/hMAM+, CK19+/hMAM-, CK19-/hMAM+, CK19+/EpCAM+, CK19-/EpCAM+, CK19+/EpCAM-, hMAM+/EpCAM+, and hMAM+/EpCAM-. After 2 years of follow-up, the presence of CTCs with triple-marker positive in peripheral blood was an independent risk factor for reduced progression-free survival (PFS) and overall survival (OS), and the presence of CTCs before any chemotherapy predicts poor OS and PFS in patients with MBC.
Cell biochemistry and biophysics 09/2012; · 3.34 Impact Factor
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ABSTRACT: This study aims to analyze 30 cases of primary pulmonary lymphoma (PPL) including treatment as well as follow-up information during the past 10 years and to investigate the correlation between microvessel density (MVD) and survival in patients with PPL. We reviewed all patients from October 2000 to October 2010. Patient demographics such as survival, recurrence, time to follow-up, and treatment mode were recorded. We also assessed MVD in the pretreated pulmonary lymphoma tissues of 30 previously untreated patients using α-CD34 immunohistochemical staining. The median age of the 30 patients was 46.9 years. With a median follow-up of 4.3 years (range, 2 to 10 years), the 5-year overall survival (OS) rate was 57 % and progression-free survival (PFS) was 44 %. High MVD, elevated serum lactate dehydrogenase (LDH), and B symptoms was significantly correlated with clinical features and shorter PFS (P (MVD) = 0.021, P (LDH) = 0.023, and P (B symptoms) = 0.005) and OS (P (MVD) = 0.028, P (LDH) = 0.032, and P (B symptoms) = 0.001). Application of surgical treatment improved the PFS (P = 0.024) and OS (P = 0.028) of patients with stage IE disease (patients who were nodal negative). The patient's stage predicted the outcome and guides the use of treatments. Patients with high MVD measured in the microenvironment had worse PFS/OS than those with low MVD expression. Patients who had B symptoms or elevated serum LDH had poor prognosis. Patients with lymph node involvement (stage IIE or greater) had poor prognosis.
Tumor Biology 08/2012; · 1.94 Impact Factor
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ABSTRACT: Bisphosphonates are widely used in clinical practice to prevent and treat osteoporosis and cancer-induced bone loss. Recently, analysis of results of several published observational studies found that women who used bisphosphonates had a significant reduction in the risk of breast cancer compared with nonusers. However, the findings were inconsistent. We systematically searched MEDLINE and EMBASE databases through June 1, 2011. The eligibility determination and the data extraction were conducted independently by 2 of the authors. A random-effect model was used to obtain the pooled estimates of effect. We identified 2 cohort studies and 2 case-control studies that were eligible for analysis, which involved 15,363 patients with breast cancer and 84,931 bisphosphonate users. The results of our meta-analysis revealed that women who received bisphosphonates have a 15% risk reduction of any breast cancer (pooled risk ratio [RR], 0.85 [95% confidence interval {CI}, 0.74-0.98]; P = .03) and a 32% risk reduction of invasive breast cancer (pooled RR, 0.68 [95% CI, 0.59-0.80]; P < .001) compared with nonusers. In addition, there was a significant dose-response relationship between the duration of bisphosphonate use and breast cancer risk. A significantly protective effect of bisphosphonates was observed in patients who used bisphosphonates for more than 1 year before the diagnosis of breast cancer compared with nonusers. The bisphosphonate users had a risk reduction of breast cancer by 8% (pooled RR, 0.92 [95% CI, 0.87-0.96]; P = .001) for each additional year of the duration of bisphosphonate use. The use of bisphosphonates may have a beneficial effect on breast cancer risk.
Clinical Breast Cancer 05/2012; 12(4):276-81. · 2.38 Impact Factor
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ABSTRACT: Suppression of cell spreading and migration by inhibitor of growth 4 suggests that its loss may induce metastasis. Inhibitor of growth 4 expression level in 60 breast cancer tissues, 30 normal adjacent tissues, and tissues from patients with benign hyperplasia was determined by real-time polymerase chain reaction, Western blot, and immunohistochemistry. The correlation between inhibitor of growth 4 expression and clinical stage, histologic grade, and microvessel density in breast cancer was analyzed. Inhibitor of growth 4 messenger RNA and protein expression in breast cancer was significantly lower than that observed in adjacent normal and hyperplastic breast tissues (P < .05). Inhibitor of growth 4 expression decreased with increasing clinical stage and histologic grade. Moreover, the presence of lymph node metastasis was correlated with decreased inhibitor of growth 4 messenger RNA expression (P < .01), and a negative correlation was noted between inhibitor of growth 4 protein expression and microvessel density in breast cancer. Inhibitor of growth 4 may represent an important biomarker for assessing the severity of breast cancer. Further studies are required to fully evaluate the diagnostic and possible prognostic value of determining inhibitor of growth 4 levels in breast cancer.
Human pathology 03/2012; 43(10):1611-7. · 3.03 Impact Factor
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ABSTRACT: The fatigue prevalence in breast cancer survivors is high during the endocrine treatment. However, there are few evidence-based interventions to manage this symptom. The aim of this study was to investigate the effectiveness of spore powder of Ganoderma lucidum for cancer-related fatigue in breast cancer patients undergoing endocrine therapy. Spore powder of Ganoderma lucidum is a kind of Basidiomycete which is a widely used traditional medicine in China. 48 breast cancer patients with cancer-related fatigue undergoing endocrine therapy were randomized into the experimental or control group. FACT-F, HADS, and EORTC QLQ-C30 questionnaires data were collected at baseline and 4 weeks after treatment. The concentrations of TNF-α, IL-6, and liver-kidney functions were measured before and after intervention. The experimental group showed statistically significant improvements in the domains of physical well-being and fatigue subscale after intervention. These patients also reported less anxiety and depression and better quality of life. Immune markers of CRF were significantly lower and no serious adverse effects occurred during the study. This pilot study suggests that spore powder of Ganoderma lucidum may have beneficial effects on cancer-related fatigue and quality of life in breast cancer patients undergoing endocrine therapy without any significant adverse effect.
Evidence-based Complementary and Alternative Medicine 01/2012; 2012:809614. · 4.77 Impact Factor
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ABSTRACT: Substantial evidence has demonstrated immune defects in breast cancer patients. They have decreased numbers of peripheral blood lymphocytes, but higher numbers of functionally suppressive CD4(+) CD25(+) Treg in both peripheral blood and tumor microenvironment. Constitutive high expression of CD25 is a pivotal characteristic of natural Treg cells. This study aims at investigating if CD25 variability affects breast carcinogenesis. Two polymorphisms (rs7072793 C > T, rs3118470 C > T) in the promoter of CD25 were selected and analyzed by a multiple independent case-control study to assess the association between CD25 genotypes and breast cancer risk. Genotyping a total of 1110 patients and 1060 healthy controls in Chinese populations showed that rs7072793 CT genotype had an odd ratio of 1.49 (95% confidence interval, 1.23-1.89) for developing breast cancer compared with CC genotype, the rs7072793 TT carriers had a further increased risk of breast cancer (OR = 2.11; 95% CI = 1.66-2.87). Furthermore, our transient transfection which focused on reporter gene expression modulated by CD25 promoter demonstrated that the presence of an rs7072793 T allele led to greater transcriptional activity than the C allele. Similarly, rs13347 T carriers were shown to have larger proportion of CD4(+) CD25(+) Tregs in the PBMCs than C carriers in the flow cytometry analysis. However, no significant differences were found in genotype frequencies at rs3118470 C > T site between cases and controls. Our findings suggest that rs7072793 C > T genetic variation in CD25 genes may be genetic modifier for developing breast cancer. © 2011 Wiley Periodicals, Inc.
Molecular Carcinogenesis 12/2011; · 3.16 Impact Factor
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ABSTRACT: The objectives of this study are to explore the clinical features and treatment outcomes and to investigate the correlation between microvessel density (MVD) and survival in patients with angioimmunoblastic T-cell lymphoma (AITL). We retrospectively analyzed clinical and follow-up data of 31 patients treated in two hospitals during 1995-2009 histologically proven AITL. We also assessed MVD in the lump of 31 previously untreated patients using α-CD34 immunohistochemical staining. The median age of the 31 patients was 48 years, eighty percent of the patients were in an advanced stage. 67.7% of them had B symptoms, with the follow-up of 2-13 years, the 5-year overall survival rate was 25.8%. The response rates (RR) of CHOP group and COP (cyclophosphamide, vincristine and prednisolone) group are 76.5 and 75%, respectively, which is no significant difference (P = 0.894). RR did not differ whether chemotherapy regimens contained anthracycline or not. The 3-year PFS rate for patients who received COP and CHOP regimen was 25.4 and 35.3% (P = 0.562), while 5-year OS rates were 25.0 and 29.4%, respectively (P = 0.667). The median PFS for patients with high MVD and low MVD were 15.1 and 30.0 months (P = 0.048), while the median OS were 20 and 45 months, respectively (P = 0.038). Patients who were sensitive to initial chemotherapy COP regimen have the similar therapeutic effect to CHOP regimen. Patients with high MVD measured in the microenvironment had worse PFS and OS than AITL patients with low expression.
Medical Oncology 10/2011; 29(4):2311-6. · 2.14 Impact Factor
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Breast Cancer Research and Treatment 07/2011; · 4.43 Impact Factor
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ABSTRACT: Triple-negative breast cancer (TNBC) has a poor prognosis and lacks prognostic indicators. The androgen receptor (AR) and E-cadherin are involved in the pathogenesis of breast cancer, but their roles are not clearly defined. We designed this study to evaluate AR and E-cadherin expression and to determine their relationships with the clinicopathologic parameters of triple-negative breast cancer. The present study included 127 TNBC patients. Immunohistochemical stains for AR and E-cadherin were performed, and the relationships between AR and E-cadherin expression and clinicopathologic data and prognosis were analyzed. We found that in TNBC patients, AR was expressed in 16(12.6%) cases, and E-cadherin was expressed in 41(33.0%) cases. AR expression was associated with tumor grade (P = 0.004) and menopausal status (P = 0.017), and E-cadherin expression was associated with node status (P= 0.016). A multivariate analysis demonstrated that tumor size, tumor grade, lymph node status, and E-cadherin were of prognostic significance for disease-free interval and overall survival. Compared with AR-positive patients, AR-negative patients showed significantly poorer outcomes with respect to the disease-free interval (P = 0.047) and overall survival (P = 0.038). E-cadherin-negative patients experienced shorter disease-free interval (P = 0.016) and poorer overall survival (P = 0.012) than did E-cadherin-positive patients. An AR-positive and E-cadherin-negative expression profile was associated with recurrence or metastasis (P = 0.036). Moreover, as the expression of nuclear AR increased (25% vs. 33.3%, P = 0.361), less E-cadherin staining was observed in TNBC samples. This finding suggested that AR and E-cadherin expression could be a useful prognostic marker for classifying subgroups of TNBC.
Medical Oncology 04/2011; 29(2):526-33. · 2.14 Impact Factor
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ABSTRACT: Acquired resistance to doxorubicin has become a serious obstacle in breast cancer treatment. The underlying mechanism responsible for this has not been completely elucidated. In this study, a doxorubicin-resistant MCF-7/Dox cell was developed to mimic the occurrence of acquired doxorubicin resistance. We next contrasted the expression profiles of ICBP90 and Topo IIα and tumor cell growth of different breast cancer cell lines to doxorubicin. Decreased expression levels of ICBP90 and Topo IIα were found in doxorubicin-resistant cells. To examine its function in chemoresistance, RNA interference (RNAi) and forskolin stimulation experiments further demonstrated that ICBP90 and Topo IIα were involved in the proliferation of cells that had acquired doxorubicin resistance. In MCF-7/Dox and ICBP90-siRNA cells, the cell growth wasn't inhibited by doxorubicin and preferentially arrested in G1 phase. However, after forskolin increased the Topo IIα expression, these breast cancer cells were again found to be inhibited by doxorubicin. Further, immunohistochemical assay breast cancer patients accepted EFC regimen showed ICBP90 was significantly associated with tumor cell proliferation, locally advanced disease and Topo IIα expression. In conclusion, down-regulation of ICBP90 induced the descended expression of Topo IIα protein which is the target enzyme of doxorubicin.
European journal of pharmacology 02/2011; 656(1-3):33-8. · 2.59 Impact Factor
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ABSTRACT: The prognostic significance of circulating tumor cells (CTCs) in patients with breast cancer is controversial. We performed a meta-analysis of published literature to assess whether the detection of CTCs in patients diagnosed with primary breast cancer can be used as a prognostic factor. We searched Medline, Science Citation Index, and Embase databases as well as reference lists of relevant articles (including review articles) for studies that assessed the prognostic relevance of tumor cell detection in the peripheral blood (PB). A total of 24 eligible studies with 4,013 cases and 1,333 controls were included. Meta-analyses were performed using a random-effects model, using the hazard ratio (HR) and 95% confidence intervals (95% CIs) as effect measures. The positive detection of CTCs in patients was significantly associated with poor overall survival (OS) (HR = 3.00 [95% CI 2.29-3.94], n = 17, P < 0.0001) and recurrence-free survival (RFS) (HR = 2.67 [95% CI 2.09-3.42], n = 22, P < 0.0001). CTC-positive breast cancers were significantly associated with high histological grade (HR = 1.21 [95% CI 1.09-1.35], n = 34, P < 0.0001), tumor size (>2 cm) (HR = 1.12 [95% CI 1.02-1.22], n = 31, P = 0.01). and nodal status (≥1) (HR = 1.10 [95% CI 1.00-1.21], n = 32, P = 0.037), but cytokeratin-19 (CK-19) mRNA-positive CTCs were not associated with these clinicopathological parameters of breast cancer. Furthermore, the presence of CTCs was not associated with estrogen receptor (ER) negativity, progesterone receptor (PR) negativity, or human epidermal growth factor receptor type 2 (HER2) positivity. Detection of CTCs in the PB indicates poor prognosis in patients with primary breast cancer. Larger clinical studies are required to further evaluate the role of these markers in clinical practice.
Breast Cancer Research and Treatment 02/2011; 130(3):809-16. · 4.43 Impact Factor
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ABSTRACT: Aromatase inhibitors can cause joint symptoms. The purpose of this pilot study was to evaluate the feasibility of immunologic therapies for this kind of joint symptoms.
A total of 16 postmenopausal women with stage I-III breast cancer with joint symptoms related to Aromatase inhibitors were enrolled. They received immunologic therapies of thymosin α1 1.6 mg, twice a week for 4 weeks. Outcome measures included the Brief Pain Inventory-Short Form, Western Ontario and McMaster Universities Osteoarthritis index, and the Functional Assessment of Cancer Therapy-General quality of life measure. Interferon-gamma and interleukin-4 were determined to evaluate immunomodulatory activity. Paired Samples Test and linear regression analysis were used to statistics the outcome measures.
From baseline to the end of treatment, patients reported improvement in the mean Brief Pain Inventory-Short Form worst pain scores (5.7-3.4, P < 0.001), pain severity (3.9-2.9, P = 0.01), and pain-related functional interference (4.2-1.8, P < 0.001), as well as the Western Ontario and McMaster Universities Osteoarthritis function subscale and Functional Assessment of Cancer Therapy-General physical well-being (P < 0.001 and P < 0.001, respectively). No adverse events were reported. The mean serum concentrations for secretion of interferon-gamma were significantly lower (P < 0.001); serum concentrations of interleukin 4 were higher (P = 0.02).
Immunologic therapies could play a role in reducing Aromatase inhibitor- related joint symptoms in breast cancer survivors and affecting the immune system in powerful ways. The improvements of immune system were associated with aromatase inhibitor-related joint symptoms.
American journal of clinical oncology 12/2010; 33(6):557-60. · 2.21 Impact Factor
