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1.  14-3-3ζ Cooperates with ErbB2 to Promote Progression of Ductal Carcinoma in Situ to Invasive Breast Cancer by Inducing Epithelial-Mesenchymal Transition 
Cancer cell  2009;16(3):195-207.
ErbB2, a metastasis-promoting oncoprotein, is overexpressed in ~25% of invasive/metastatic breast cancers, but in 50–60% of non-invasive ductal carcinomas in situ (DCIS). It has been puzzling how a subset of ErbB2-overexpressing DCIS develops into invasive breast cancer (IBC). We found that co-overexpression of 14-3-3ζ in ErbB2-overexpressing DCIS conferred a higher risk of progression to IBC. ErbB2 and 14-3-3ζ overexpression, respectively, increased cell migration and decreased cell adhesion, two prerequisites of tumor cell invasion. 14-3-3ζ overexpression reduced cell adhesion by activating the TGFβ/Smads pathway that led to ZFHX1B/SIP-1 upregulation, E-cadherin loss, and epithelial-mesenchymal transition (EMT). Importantly, patients whose breast tumors overexpressed both ErbB2 and 14-3-3ζ had higher rates of metastatic recurrence and death than those whose tumors overexpressed only one.
PMCID: PMC2754239  PMID: 19732720
2.  14-3-3ζ Overexpression Defines High Risk for Breast Cancer Recurrence and Promotes Cancer Cell Survival 
Cancer research  2009;69(8):3425-3432.
The ubiquitously expressed 14-3-3 proteins are involved in numerous important cellular functions. The loss of 14-3-3σ is a common event in breast cancer; however, the role of other 14-3-3s in breast cancer is unclear. Recently, we found that 14-3-3ζ overexpression occurs in early stage breast diseases and contributes to transformation of human mammary epithelial cells. Here, we show that 14-3-3ζ overexpression also persisted in invasive ductal carcinoma and contributed to the further progression of breast cancer. To examine the clinical impact of 14-3-3ζ overexpression in advanced stage breast cancer, we performed immunohistochemical analysis of 14-3-3ζ expression in primary breast carcinomas. 14-3-3ζ overexpression occurred in 42% of breast tumors and was determined to be an independent prognostic factor for reduced disease-free survival. 14-3-3ζ overexpression combined with ErbB2 overexpression and positive lymph node status identified a subgroup of patients at high risk for developing distant metastasis. To investigate whether 14-3-3ζ overexpression causally promotes breast cancer progression, we overexpressed 14-3-3ζ by stable transfection or reduced 14-3-3ζ expression by siRNA in cancer cell lines. Increased 14-3-3ζ expression enhanced anchorage independent growth and inhibited stress-induced apoptosis, whereas downregulation of 14-3-3ζ reduced anchorage independent growth and sensitized cells to stress-induced apoptosis via the mitochondrial apoptotic pathway. Transient blockade of 14-3-3ζ expression by siRNA in cancer cells effectively reduced the onset and growth of tumor xenografts in vivo. Therefore, 14-3-3ζ overexpression is a novel molecular marker for disease recurrence in breast cancer patients and may serve as an effective therapeutic target in patients whose tumors overexpress 14-3-3ζ.
PMCID: PMC2671640  PMID: 19318578
14-3-3ζ; breast cancer; apoptosis resistance; disease recurrence; prognostic marker
3.  Hemoglobin levels and anemia evaluation during pregnancy in the highlands of Tibet: a hospital-based study 
BMC Public Health  2009;9:336.
Anemia is regarded as a major risk factor for unfavorable pregnancy outcomes, but there have been no previous studies describing the pattern of hemoglobin concentration during pregnancy in Tibet and the relationship between altitude and Hb concentration in the pregnant women living in Tibet still has not been clearly established. The main objectives of this study were to study the hemoglobin levels and prevalence of anemia among pregnant women living in the highlands of Tibet and to evaluate potential associations of hemoglobin and anemia with women's characteristics.
The hospital-based study was conducted in 380 pregnant women. Their blood samples were tested and related sociodemographic information was collected. Multiple linear regression model and multiple logistic regression model were used to assess the association of pregnant women's characteristics with hemoglobin level and the occurrence of anemia. Centers for Disease Control (CDC), Dirren et al. and Dallman et al. methods were used to adjust the hemoglobin measurements based on altitude for estimating the prevalence of anemia.
The mean hemoglobin concentration was 127.6 g/L (range: 55.0-190.0 g/L). Prevalence rate of anemia in this study was 70.0%, 77.9% and 41.3%, respectively for three altitude-correction methods for hemoglobin (CDC method, Dirren et al. method, and Dallman et al. method). Gestational age, ethnicity, residence and income were significantly associated with the hemoglobin concentration and prevalence of anemia in the study population. Specially, the hemoglobin concentration of pregnant women decreased with increase in gestational age.
The hemoglobin level was low and prevalence rate of anemia was high among pregnant women in Lhasa, Tibet. Gestational age, ethnicity, residence and income were found to be significantly associated with the hemoglobin level and the occurrence of anemia in the study population.
PMCID: PMC2753353  PMID: 19754927
4.  Evaluation of a portable hemoglobin photometer in pregnant women in a high altitude area: a pilot study 
BMC Public Health  2009;9:228.
Anemia is a widespread public health problem associated with an increased risk of morbidity and mortality, especially in pregnant women. This study examined the agreement between a portable hemoglobin photometer and a laboratory analyzer in determining hemoglobin level in pregnant women.
This study recruited 69 pregnant women in Tibet, China. Capillary blood samples were taken to measure hemoglobin concentration using the hemoglobin photometer and the laboratory analyzer. Limit of agreement, concordance and intraclass correlation coefficient were used to evaluate the agreement. Laboratory measurement was considered as the standard reference method. Sensitivity and specificity were calculated to assess the error in screening for anemia.
Mean difference between the two methods was -2.1 g/l. wide 95% limits of agreement were found (-22.6 g/l to 18.4 g/l). The intraclass correlation coefficient was 0.795, and concordance correlation coefficient was 0.793. Sensitivity and specificity were 94.9% and 76.7% respectively. Positive predictive value was 84.1%, and negative predictive value was 92.0%.
This hemoglobin photometer is not recommended for determining hemoglobin concentration in pregnancy in a high altitude area.
PMCID: PMC2717084  PMID: 19591672

Results 1-4 (4)