Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: A meta-analysis of prospective cohort studies.

BACKGROUND & AIMS: Previous studies implied that dietary isoflavone intake may reduce the risk of developing breast cancer, but some have shown ambiguous results. This study aimed to systematically evaluate and summarize available evidence on the effect dietary isoflavone intake has on the risk of developing breast cancer. METHODS: PubMed, Embase, and the Cochrane Library were searched for prospective cohort studies published through April 2017 that evaluated the effect of dietary isoflavone intake on the development of breast cancer. RESULTS: Sixteen prospective cohort studies, involving 11,169 breast cancer cases and 648,913 participants, were identified and included in our data analysis. The pooled relative risk (RR) of breast cancer was 0.99 for high versus low intake of isoflavones (95% confidence interval [CI], 0.91-1.09; P = 0.876) and 0.99 for moderate versus low intake of isoflavones (95%CI, 0.92-1.05; P = 0.653), with insignificant heterogeneity (P = 0.187 for high versus low, and P = 0.192 for moderate versus low). While a moderate consumption of soy-based foods did not significantly affect breast cancer risk, a high intake of soy-based foods associated with a lower risk of developing breast cancer. Considering specific foods, an increased the risk of developing breast cancer was seen with a moderate intake of formononetin, but no significant associations were found between breast cancer risk and other isoflavone-rich diets. CONCLUSIONS: The present meta-analysis indicates that women with a high dietary intake of soy foods may experience a statistically significant reduction in breast cancer risk. However, moderate formononetin consumption may increase the risk of developing breast cancer.

Downregulation of RASSF6 promotes breast cancer growth and chemoresistance through regulation of Hippo signaling.

This study aims to investigate the clinical significance and biological function of RASSF6 in human breast cancers. RASSF6 protein was found to be downregulated in 42 of 95 human breast cancer tissues by immunohistochemistry, which was associated with advanced TNM stage and nodal metastasis. The rate of RASSF6 downregulation was higher in Triple-negative breast cancer (TNBC). Downregulation of RASSF6 protein was also found in breast cancer cell lines, especially in TNBC cell lines. Overexpression RASSF6 inhibited cell growth rate and colony formation ability in MDA-MB-231 cell line. Depletion of RASSF6 promoted proliferation rate and colony formation ability in T47D cell line. Flow cytometry/PI staining demonstrated that RASSF6 inhibited cell cycle transition. AnnxinV/PI analysis showed that RASSF6 overexpression upregulated apoptosis induced by cisplatin (CDDP) while RASSF6 depletion inhibited apoptosis. JC-1 staining showed that RASSF6 overexpression inhibited mitochondrial membrane potential. Western blot analysis demonstrated that RASSF6 repressed cyclin D1, YAP while upregulated p21, cleaved caspase 3 and cytochrome c expression. In addition, RASSF6 activated Hippo signaling pathway by upregulating MST1/2 and LATS1 phosphorylation. Restoration of YAP inhibited cleaved caspase 3 and cytochrome c which were induced by RASSF6. Restoration of YAP also reduced the rate of CDDP induced apoptosis. In conclusion, this study provided evidence that RASSF6 functions as a potential tumor suppressor in human breast cancer through activation of Hippo pathway.

TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway.

Dysregulation of TRIM32 has been implicated in several human cancers, however, its clinical significance and biological function in breast cancer have not been investigated. Using immunohistochemistry, we found that TRIM32 expression is upregulated in breast cancer tissues and that it correlates with advanced stage and poor prognosis. TRIM32 is also overexpressed in 4/7 breast cancer cell lines. CCK8 and colony formation assays showed that TRIM32 depletion inhibited proliferation and colony formation in the T47D cell line, while TRIM32 overexpression promoted MCF-7 cell growth and colony formation. Cell viability and Annexin V/PI staining demonstrated that TRIM32 maintained breast cancer cell survival and reduced apoptosis rate when cells were treated with cisplatin. Western blot analysis demonstrated that TRIM32 overexpression resulted in an upregulation of p-IκB, p-p65, cIAP1, and cIAP2 and a downregulation of p21 and p27 in MCF-7 cells. TRIM32 depletion in T47D cells demonstrated the opposite results, suggesting that TRIM32 may activate the NF-κB pathway. The NF-κB inhibitor BAY 11-7082 blocked the effects of TRIM32 on cisplatin resistance and cIAP1/2 protein regulation. Taken together, the present study demonstrates that TRIM32 downregulates p21/p27 and upregulates IAP family proteins to facilitate breast cancer cell growth and inhibit drug-induced apoptosis, possibly through the NF-κB signaling pathway.

Improved galvanic replacement growth of Ag microstructures on Cu micro-grid for enhanced SERS detection of organic molecules.

Galvanic growth of Ag nano/micro-structures on Cu micro-grid was systematically studied for surface-enhanced Raman scattering (SERS) applications. Detailed characterizations via FE-SEM and HR-TEM showed that processing parameters, (reaction time, Ag(+) concentration, and PVP addition) all substantially affect thermodynamics/kinetics of the replacement reaction to yield substrates of significantly different microstructures/homogeneities and thus varied SERS performances (sensitivity, enhancement factor, and reproducibility) of the Ag substrates in the detection of R6G analyte. PVP as an additive was shown to notably alter nucleation/growth behaviors of the Ag crystals and promote the deposition of dense and uniform Ag films of nearly monodisperse polyhedrons/nanoplates through suppressing dendrites crystallization. Under optimized synthesis (50mM of Ag(+), 30s of reaction, and 700 wt.% of PVP), Ag substrates exhibiting a high Raman signal enhancement factor of ~1.1 × 10(6) and a low relative standard deviation of ~0.13 in the repeated detection of 10 µM R6G were obtained. The facile deposition and excellent performance reported in this work may allow the Ag microstructures to find wider SERS applications. Moreover, growth mechanisms of the different Ag nano/micro-structures were discussed based on extensive FE-SEM and HR-TEM analysis.

Prognostic significance of body mass index in breast cancer patients with hormone receptor-positive tumours after curative surgery.

PURPOSE: Obesity has been recognized as a significant risk factor for postmenopausal breast cancer. The aim of this study is to investigate the prognostic significance of body mass index (BMI) in hormone receptor-positive, operable breast cancer. METHODS: In this retrospective cohort study, 1,192 consecutive patients with curative resection of primary breast cancer were enrolled. Patients were assigned to two groups according to BMI: normal or underweight (BMI < 23.0 kg/m²) and overweight or obese (BMI ≥ 23.0 kg/m²). Associations among BMI and clinicopathological characteristics and prognosis of patients were assessed. RESULTS: A high BMI was significantly (P < 0.01) correlated with age, nodal stage, ALNR, ER positivity, PR positivity and menopausal status at diagnosis. Univariate analysis revealed that BMI, pathologic T stage, nodal stage, axillary lymph node ratio (ALNR) and adjuvant radiotherapy history were significantly (P < 0.05) associated with disease-free survival and overall survival, irrespective of tumour hormone receptor status. Multivariate analysis revealed BMI as an independent prognostic factor in all cases and in hormone receptor-positive cases. CONCLUSION: A high BMI (≥ 23.0 kg/m²) is independently associated with poor prognosis in hormone receptor-positive breast cancer.

[Influence of the number of removed axillary lymph nodes on the prognosis of node-negative primary breast cancer].

OBJECTIVE: To analyze the relationship between the number of removed axillary lymph nodes and prognosis of axillary node-negative breast cancer. METHODS: The clinicopathological data of 655 patients with breast cancer were analyzed retrospectively. The disease-free survival curves were generated according to the number of removed axillary lymph nodes using Kaplan-Meier plots. The correlation between the co-variables and rate of breast cancer-related events was analyzed using Cox model. RESULTS: The overall five year-disease free survival rate of the 655 cases was 94.4%. The rate of patients with lymph node number ≤ 12 was 90.3%, and that of lymph node number > 12 was 96.5%, with a statistically significant difference (P = 0.009). Significantly less breast cancer-related events were observed in patients with lymph node number > 12 (15/426, 3.5%) than that in patients with lymph node number ≤ 12 (22/229, 9.6%) (P = 0.009). CONCLUSIONS: When axillary node dissection is indicated, dissection of lymph nodes >12 leads to much less breast cancer-related events than that in patients with dissected lymph node ≤ 12. The more lymph nodes are dissected, the more accurate prognosis can be estimated.

Study on the skip metastasis of axillary lymph nodes in breast cancer and their relation with Gli1 expression.

The skip metastasis (SM) of axillary lymph nodes (ALN) in breast cancer is an important phenomenon which is crucial to determine the correct choice of surgical resection. The mechanism of SM of ALN is unclear. Gli1 protein is a core epithelial-to-mesenchymal transition (EMT) regulatory factor that plays essential roles in both development and disease processes and has been associated with metastasis in carcinomas. The aim of this study was to investigate the clinicopathological characteristics of SM and evaluate the significance of Gli1 expression in breast cancer patients with metastasis of ALN. Clinicopathological data from 1,037 female breast cancer patients who underwent radical mastectomy were retrospectively reviewed. In this study, an SM was defined as level I absence but level II and/or level III involvement. The expression of Gli1 was evaluated by immunohistochemistry in 102 non-SM cases with positive nodes and 33 SM cases. In univariate analysis, we found that pN category, TNM stage, intrinsic subtypes and Gli1 expression was significant risk factor of SM. Further logistic regression analysis revealed that luminal A cases had a lower risk of SM relative to luminal B 1 (HER2 negative) cases. Further multivariate analysis revealed that Gli1 expression and numbers of positive lymph nodes were the independent factors which associated with SM. Collectively, Breast cancer with SM of ALN associated with the intrinsic subtype of the luminal B1. Gli1 expression related with the procession of breast cancer with SM, which can be used as a predictor of SM of ALN in breast cancer.

Fascin, an actin-bundling protein, promotes breast cancer progression in vitro.

Fascin, an actin-cross-linking protein, is up-regulated in breast cancer and correlates with a more aggressive disease. This study was conducted to elucidate the effects of manipulating fascin in breast cancer cells on the metastasis-associated events, including proliferation, adhesion, invasion, epithelial-mesenchymal transition (EMT) and enrichment of a CD44(+) /CD24(-) subpopulation that show some stem/progenitor cell properties. Western blot analysis of a panel of breast cancer cell lines revealed high expression of fascin in MDA-MB-435 and MDA-MB-231 cells but revealed no or low expression in MDA-MB-453, Her-18 and T47D. Gain-of-function and loss-of-function studies in breast cancer cells demonstrated that forced expression of fascin promoted cell proliferation assessed by the MTT assay, decreased cellular adhesion to fibronectin and potentiated the invasive capacity in the Transwell chamber invasion assay. Conversely, down-regulation of fascin via small interfering RNA increased cell adhesion and facilitated cell proliferation and invasion. In addition, fascin participated in the EMT and modulated the proportion of the CD44(+) /CD24(-) subpopulation in breast cancer cells. In conclusion, our data highlight an important role for fascin in breast cancer progression in vitro through orchestrating a variety of cellular events associated with metastasis, and thus, targeting this gene might have therapeutic implications.

Clinical and biological significance of hepsin overexpression in breast cancer.

OBJECTIVE: Although many studies have documented the tumor-promoting role of hepsin in several types of malignancies, little is known about its clinical and biological significance in breast cancer. MATERIALS AND METHODS: Hepsin expression was examined in 4 pairs of fresh breast tumor samples and corresponding nontumor breast tissues by Western blotting. Immunohistochemistry for hepsin was performed on an additional cohort of 215 archival breast cancer samples. The clinical significance of hepsin expression was analyzed. Knockdown of hepsin expression was performed in 2 breast cancer cell lines, MDA-MB-231 and HER18, with a high abundance of endogenous hepsin, and the effects of hepsin silencing on cell invasion and proliferation were evaluated. RESULTS: Hepsin was aberrantly overexpressed in breast cancer tissues relative to adjacent nontumor tissues. Its overexpression was significantly associated with tumor stage (P = 0.037), lymph node metastasis (P = 0.010), estrogen receptor positivity (P = 0.019), and progesterone receptor positivity (P < 0.0001) in patients with breast cancer. Down-regulation of hepsin expression by small interfering RNA (siRNA) significantly reduced cell proliferation and invasion in both the MDA-MB-231 and HER18 cells compared to nonspecific control small interference RNA. CONCLUSION: Our data demonstrate that hepsin expression is frequently up-regulated in breast cancer tissues, which is associated with tumor growth and progression. Thus, inhibition of hepsin expression might be of therapeutic significance.

Fluorine- and iron-modified hierarchical anatase microsphere photocatalyst for water cleaning: facile wet chemical synthesis and wavelength-sensitive photocatalytic reactivity.

High photocatalytic efficiency, easy recovery, and no biological toxicity are three key properties related to the practical application of anatase photocatalyst in water cleaning, but seem to be incompatible. Nanoparticles-constructed hierarchical anatase microspheres with high crystallinity and good dispersion prepared in this study via one-step solution processing at 90 degrees C under atmospheric pressure by using ammonium fluotitanate as the titanium source and urea as the precipitant can reconcile these three requirements. The hierarchical microspheres were found to grow via an aggregative mechanism, and contact recrystallization occurred at high additions of the FeCl(3) electrolyte into the reaction system. Simultaneous incorporation of fluorine and iron into the TiO(2) matrix was confirmed by combined analysis of X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and UV-vis absorption spectroscopy. Surface structure and morphology changes of the microspheres induced by high-temperature annealing were clearly observed by field-emission scanning electron microscopy, especially for the phase-transformed particles. The original nanoparticles-constructed rough surfaces partially became smooth, resulting in a sharp drop in photocatalytic efficiency. Interestingly, iron loading has detrimental effects on the visible-light photocatalytic activity of both the as-prepared and the postannealed anatase microspheres but greatly enhances the photocatalytic activity of the as-prepared anatase microspheres under UV irradiation. No matter under UV or visible-light irradiation, the fluorine-loaded anatase microspheres and especially the postannealed ones show excellent photocatalytic performance. The underlying mechanism of fluorine and iron loading on the photocatalytic efficacy of the anatase microspheres was discussed in detail. Beyond photocatalytic applications, this kind of material is of great importance to the assembling of photoactive photonic crystal that can control light motion.

Expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas.

BACKGROUND: Biomarkers in breast neoplasms provide invaluable information regarding prognosis and help determining the optimal treatment. We have examined the possible correlation between cancer stem cell (CSC)-like markers (CD133, paired box gene 2 protein (PAX2), epithelial specific antigen (ESA)), and a new membrane estrogen receptor (G-protein coupled receptor 30 (GPR30)) in invasive ductal breast carcinomas with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers. METHODS: In 74 invasive ductal breast carcinomas, we investigated the protein expression of these molecular markers by immunohistochemistry, and their associations with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers. We studied the interrelationship between the expressions of these proteins. RESULTS: CD133, a putative CSC marker, was positively related to tumor size, tumor stage, and lymph node metastasis. PAX2 was negatively correlated with tumor recurrence. ESA, one of the breast CSC markers, was an indicator of tumor recurrence. GPR30 was associated with hormone receptors. Despite the correlation between GPR30 and the nuclear estrogen receptor, the expression was dependent. Positive staining of GPR30 in tumors displayed a significant association with high C-erbB2 expression and a tendency for tumor recurrence. A positive relationship between GPR30 and CD133 existed. CONCLUSION: Detecting the expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas may be of help in more accurately predicting the aggressive properties of breast cancer and determining the optimal treatment.

[Clinical evaluation of full-field digital mammography and breast imaging reporting and data system on breast diseases].

OBJECTIVE: To evaluate the values of full-field digital mammography (FFDM) and breast imaging reporting and data system (BI-RADS) on breast diseases. METHODS: Eight hundreds and thirty-one patients with 871 focuses were analyzed who underwent imaging examinations with FFDM before operation during January 1, 2004 to December 31, 2005. All patients received operation and had identified pathological diagnosis including breast cancer, breast fibroma, intraductal papilloma and breast disease. The radiological diagnosis followed BI-RADS suggested by American College of Radiology. RESULTS: The imaging diagnostic sensitivity of overall focuses was 80.9%, the specificity was 90.0%, the positive predictive value was 88.4%, the negative predictive value was 83.3% and the diagnose accuracy was 85.5%. Two hundreds and sixty cases (97.7%) were pathological diagnosed breast cancer in BI-RADS category V, 67.8% (82/121) in BI-RADS category IV and 16.7% (81/484) in BI-RADS category I-III. CONCLUSIONS: When the radiological diagnosis is BI-RADS category V, surgery biopsy is the option. To category IV focuses, surgery biopsy or stereotactic vacuum-assisted biopsy should be suggested. As to category I-III focuses, the management should be prudent, and other factors should be considered including the social and economic factors.

[Performance of 18F-FDG PET/CT in the detection of primary breast cancer and staging of the regional lymph nodes].

OBJECTIVE: To evaluate the performance of 18F-FDG PET/CT in the detection of primary breast cancer, and the staging of regional lymph nodes. METHODS: Twenty four females with highly suspected breast cancer, underwent PET/CT imaging of the breast preoperatively. All the patients received no treatment at admission. Three nuclear medicine physicians analyzed the image and made the diagnosis. 32 breast lesions were evaluated by histology, revealing 25 breast carcinomas and 7 benign pathological changes. 23 patients had histological diagnosis of the breast tumor and regional lymph nodes. RESULTS: 20 of 25 breast carcinomas were successfully diagnosed by FDG-PET/CT. The sensitivity was 80% and specificity was 71.4%. No Tis breast carcinoma was detected. 75.0% of T1 breast carcinomas were detected, and with 85.7% of stage T2, 100.0% of T3. 10 patients were proved to have lymph node metastasis, and PET/CT got a sensitivity of 60.0%. As to a suspicious distant metastasis, PET/CT convinced the diagnosis. CONCLUSION: As a noninvasive technique, FDG PET/CT appears to be a useful method in staging patient with breast cancer, especially in cases in which the lesion is hard to predict by routine examination. But the accuracy of FDG PET/CT seems to be not high enough to identify patients who might avoid axillary lymph nodes dissection. In the detection of breast lesions, PET/CT doesn't seem to have a high sensitivity, especially in early stage breast cancers. The high cost and the space resolution limit its use as a routine diagnostic method of breast cancer.

Phase structure and luminescence properties of Eu3+-doped TiO2 nanocrystals synthesized by Ar/O2 radio frequency thermal plasma oxidation of liquid precursor mists.

Eu3+-doped TiO2 luminescent nanocrystals have been synthesized in this work via Ar/O2 thermal plasma oxidizing mists of liquid precursors containing titanium tetra-n-butoxide and europium(III) nitrate, with varied O2 input in the plasma sheath (10-90 L/min) and Eu3+ addition in the precursor solution (Eu/(Ti + Eu) = 0-5 atom%). The resultant nanopowders are mixtures of the anatase (30-36 nm) and rutile (64-83 nm) polymorphs in the studied range, but the rutile fraction increases steadily at a higher Eu3+ addition, as revealed by X-ray diffraction (XRD) and Raman spectroscopy, because of the creation of oxygen vacancies in the TiO2 gas clusters by substitutional Eu3+ doping. The amount of Eu3+ that can be doped into a TiO2 lattice was limited up to 0.5 atom%, above which Eu2Ti2O7 pyrochlore was formed in the final products. High resolution transmission electron microscopy (HRTEM) observation indicates that the particles are dense and have sizes ranging from several nanometers up to 180 nm. Efficient nonradiative energy transfer from the TiO2 host to Eu3+ ions, which was seldom reported in the wet-chemically derived nanoparticles or thin films of the current system, was confirmed by combined studies of excitation, UV-vis (ultraviolet-visible), and PL (photoluminescence) spectroscopy. As a consequence of this, bright red emissions were observed from the plasma-generated nanopowders either by exciting the TiO2 host with UV light shorter than 405 nm or by directly exciting Eu3+ at a wavelength beyond the absorption edge (405 nm) of TiO2.

[Research on the association between different levels of serum iron and essential hypertension].

OBJECTIVE: To study the relationship between serum iron(SI) and essential hypertension (EHT) based on population-based samples. METHODS: Using clustering multistage sampling method, all the people above 18 years old in the target population were investigated. Blood pressure was measured and the questionnaire was used to find out related factors. Five milliliters fast vein blood were drawn and the serum were used for testing on serum iron (SI) and other elements such as blood sugar, cholesterol (CHOL), triglyceride (TG), high density lipoprotein(HDL-C), low density lipoprotein (LDL-C), serum sodium, serum potassium, serum calcium etc. A case control study was carried out with EHT patients from the selected population as case group, and the other healthy peoples as controls. Database was created by Fox Pro and SPSS 10.0 was used for statistical analysis. RESULTS: The concentrations of SI, with (17.75 +/- 7.66) micromol/ L in EHT group and (17.23 +/- 7.83) micromol/L in control group, showed statistical difference (P < 0.05) between the two groups. The concentrations of SI also showed statistical difference (P < 0.05) between the high DBP and normal group with the average level as (17.84 +/- 7.58) micromol/L in high DBP group and (17.26 +/- 7.85) micromol/L in normal group. Data from monovariate analysis showed that the increase of SI was a risk factor for EHT, DBP and SBP. By multivariate analysis for EHT, while SI still existed in the model (OR = 1.296, 95% CI: 1.057-1.590), but for SBP the results almost remained the same (OR = 1.285, 95% CI:1.102-1.498). CONCLUSION: Data from the results showed that SI was probably a risk factor for EHT.

[The epidemiological survey of prevalence rate of hypertension in the countryside of Zhangwu county, Liaoning province].

OBJECTIVE: To investigate the prevalence state of essential hypertension in the countryside of Zhangwu county, Liaoning province to confirm whether this county is the high prevalence region of essential hypertension. METHODS: Five thousand, two hundred and eight 15-year olds or older were sampled by means of whole population random sampling. Blood pressure was measured and the related risk factors were investigated with the uniform questionnaire. SPSS 10.0 of statistical software was used for data analysis. RESULTS: The standardized prevalence rate of hypertension was 35.0% at this region, 40.0% in male, 32.0% in female. The prevalence rates of hypertension were increased with the increasing of the age in both males and females. There were significant statistically differences in the prevalence rates of hypertension between the different age groups, different countrysides and different villages. The standardized prevalence rate of hypertension were 43.0% the highest and 29.0% lowest respectively in the countryside, with prevalence rates, were 59.4% highest and 26.9% lowest respectively in the village. In all the patients with hypertension, 72.0% having hypertension II, III. CONCLUSION: The countryside of Zhangwu county was a high prevalence region of essential hypertension which was unusual in our country. The reason of this status was still unknown which called for further study.