Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors.

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2 (HER2)-positive (+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown. Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab. Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model. Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

Genomic and transcriptomic analysis of breast cancer identifies novel signatures associated with response to neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has become a standard treatment strategy for breast cancer (BC). However, owing to the high heterogeneity of these tumors, it is unclear which patient population most likely benefit from NAC. Multi-omics offer an improved approach to uncovering genomic and transcriptomic changes before and after NAC in BC and to identifying molecular features associated with NAC sensitivity. METHODS: We performed whole-exome and RNA sequencing on 233 samples (including matched pre- and post-treatment tumors) from 50 BC patients with rigorously defined responses to NAC and analyzed changes in the multi-omics landscape. Molecular features associated with NAC response were identified and validated in a larger internal, and two external validation cohorts, as well as in vitro experiments. RESULTS: The most frequently altered genes were TP53, TTN, and MUC16 in both pre- and post-treatment tumors. In comparison with pre-treatment tumors, there was a significant decrease in C > A transversion mutations in post-treatment tumors (P = 0.020). NAC significantly decreased the mutation rate (P = 0.006) of the DNA repair pathway and gene expression levels (FDR = 0.007) in this pathway. NAC also significantly changed the expression level of immune checkpoint genes and the abundance of tumor-infiltrating immune and stroma cells, including B cells, activated dendritic cells, γδT cells, M2 macrophages and endothelial cells. Furthermore, there was a higher rate of C > T substitutions in NAC nonresponsive tumors than responsive ones, especially when the substitution site was flanked by C and G. Importantly, there was a unique amplified region at 8p11.23 (containing ADGRA2 and ADRB3) and a deleted region at 3p13 (harboring FOXP1) in NAC nonresponsive and responsive tumors, respectively. Particularly, the CDKAL1 missense variant P409L (p.Pro409Leu, c.1226C > T) decreased BC cell sensitivity to docetaxel, and ADGRA2 or ADRB3 gene amplifications were associated with worse NAC response and poor prognosis in BC patients. CONCLUSIONS: Our study has revealed genomic and transcriptomic landscape changes following NAC in BC, and identified novel biomarkers (CDKAL1P409L, ADGRA2 and ADRB3) underlying chemotherapy resistance and poor prognosis, which could guide the development of personalized treatments for BC.

Influence of Cations on HCOOH and CO Formation during CO2 Reduction on a PdMLPt(111) Electrode.

Understanding the role of cations in the electrochemical CO2 reduction (CO2RR) process is of fundamental importance for practical application. In this work, we investigate how cations influence HCOOH and CO formation on PdMLPt(111) in pH 3 electrolytes. While only (a small amount of adsorbed) CO forms on PdMLPt(111) in the absence of metal cations, the onset potential of HCOOH and CO decreases with increasing cation concentrations. The cation effect is stronger on HCOOH formation than that on CO formation on PdMLPt(111). Density functional theory simulations indicate that cations facilitate both hydride formation and CO2 activation by polarizing the electronic density at the surface and stabilizing *CO2-. Although the upshift of the metal work function caused by high coverage of adsorbates limits hydride formation, the cation-induced electric field counterbalances this effect in the case of *H species, sustaining HCOOH production at mild negative potentials. Instead, at the high *CO coverages observed at very negative potentials, surface hydrides do not form, preventing the HCOOH route both in the absence and presence of cations. Our results open the way for a consistent evaluation of cationic electrolyte effects on both activity and selectivity in CO2RR on Pd-Pt catalysts.

Enhanced Electrochemical CO2 Reduction to Formate on Poly(4-vinylpyridine)-Modified Copper and Gold Electrodes.

Developing active and selective catalysts that convert CO2 into valuable products remains a critical challenge for further application of the electrochemical CO2 reduction reaction (CO2RR). Catalytic tuning with organic additives/films has emerged as a promising strategy to tune CO2RR activity and selectivity. Herein, we report a facile method to significantly change CO2RR selectivity and activity of copper and gold electrodes. We found improved selectivity toward HCOOH at low overpotentials on both polycrystalline Cu and Au electrodes after chemical modification with a poly(4-vinylpyridine) (P4VP) layer. In situ attenuated total reflection surface-enhanced infrared reflection-adsorption spectroscopy and contact angle measurements indicate that the hydrophobic nature of the P4VP layer limits mass transport of HCO3- and H2O, whereas it has little influence on CO2 mass transport. Moreover, the early onset of HCOOH formation and the enhanced formation of HCOOH over CO suggest that P4VP modification promotes a surface hydride mechanism for HCOOH formation on both electrodes.

Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case-Control Study in Chinese Females.

BACKGROUND: Leptin (LEP) plays a physiological role through its specific receptor (LEPR) and is involved in the occurrence and development of breast cancer. Our current study aimed at determining the influence of single-nucleotide polymorphisms (SNPs) in the genes coding for LEP and LEPR on breast cancer risk. METHODS: In the present study, 963 breast cancer cases and 953 controls were enrolled. Five SNPs of LEP and two of LEPR were chosen to evaluate the correlation of selected SNPs with breast cancer susceptibility among women in northern and eastern China. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), estrogen receptor, and progesterone receptor status. The expression patterns of risk variant-associated genes were detected by expression quantitative trait locus (eQTL) analysis with eQTLGen and The Cancer Genome Atlas database. RESULTS: There were significant differences between breast cancer cases and control groups in the menopausal status and family history of breast cancer. Two SNPs (rs1137101 and rs4655555) of the LEPR gene decreased overall breast cancer risk, and other five SNPs showed no significant association with breast cancer risk. rs1137101 (GA vs. GG; adjusted OR = 0.719, 95% CI = 0.578-0.894, p = 0.003) and rs4655555 (TT vs. AA; adjusted OR = 0.574, 95% CI = 0.377-0.873, p = 0.009) significantly decreased breast cancer risk after Bonferroni correction for multiple testing. In subgroup analyses, the GA and GA + AA genotypes of LEPR rs1137101 associated with decreased breast cancer risk in the subgroup of BMI ≤ 24 kg/m2 or WHR ≥ 0.85 after Bonferroni correction. Furthermore, we found that the expressions of rs4655555-associated gene LEPR and leptin receptor overlapping transcript (LEPROT) were upregulated in breast cancer tumor tissues compared with adjacent normal tissues, and a higher expression of LEPR in tumor tissues was correlated with poor prognosis of breast cancer patients using The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data. CONCLUSION: Our study demonstrated that the polymorphisms rs1137101 and rs4655555 located in the LEPR gene decreased breast cancer risk in Chinese females, which might be a research-worthy bio-diagnostic marker and applied for early prediction and risk assessment of breast cancer.

Prognostic value of gamma-interferon-inducible lysosomal thiol reductase expression in female patients diagnosed with breast cancer.

Because of the high heterogeneity of breast cancer outcome, identification of novel prognostic biomarkers is critical to improve patient stratification and guide precise treatment. We examined the prognostic value of gamma-interferon-inducible lysosomal thiol reductase (GILT) expression in a training set of 416 breast cancer patients and a validation set of 210 patients, and performed functional studies to investigate the functions and underlying mechanisms of GILT on breast cancer prognosis. Our results indicated that high GILT expression in breast cancer cells was associated with improved disease-free survival (DFS; hazard ratio [HR] = 0.189, 95% confidence interval [CI]: 0.099-0.361) and breast cancer-specific survival (BCSS; HR = 0.187, 95% CI: 0.080-0.437) of breast cancer patients both in the training set and the external validation set (HR = 0.453, 95% CI: 0.235-0.873 for DFS, HR = 0.488, 95% CI: 0.245-0.970 for BCSS). In vitro and in vivo studies showed that GILT overexpression inhibited breast cancer cells proliferation, invasion, migration and tumor formation in nude mice and increased sensitivity of breast cancer cells to standard treatment. Proteomics analysis indicated that GILT inhibited reactive oxygen species (ROS) and autophagy activation in breast cancer cells, and GILT overexpression-mediated tumor growth was further enhanced in the presence of autophagy or ROS inhibitors. Our results demonstrate that GILT expression can be effectively used to predict the prognosis and guide treatment strategies of breast cancer patients.

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

BACKGROUND: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. METHODS: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models. RESULTS: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (ptrend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction  = 0.0497). However, these interactions became insignificant after Bonferroni correction. CONCLUSION: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

Emergence of Potential-Controlled Cu-Nanocuboids and Graphene-Covered Cu-Nanocuboids under Operando CO2 Electroreduction.

The electroreduction of CO2 (CO2RR) is a promising strategy toward sustainable fuels. Cu is the only Earth-abundant and pure metal capable of catalyzing CO2-to-hydrocarbons conversion with significant Faradaic efficiencies; yet, its dynamic structure under operando CO2RR conditions remains unknown. Here, we track the Cu structure operando by electrochemical scanning tunneling microscopy and Raman spectroscopy. Surprisingly, polycrystalline Cu surfaces reconstruct forming Cu nanocuboids whose size can be controlled by the polarization potential and the time employed in their in situ synthesis, without the assistance of organic surfactants and/or halide anions. If the Cu surface is covered by a graphene monolayer, smaller features with enhanced catalytic activity for CO2RR can be prepared. The graphene-protecting layer softens the 3D morphological changes that Cu-based catalysts suffer when exposed to aggressive electrochemical environments and allows us to track the kinetic roughening process. This novel strategy is promising for improving Cu long-term stability, and consequently, it could be used as a platform to ultimately control product selectivity.

Adipocyte-derived SFRP5 inhibits breast cancer cells migration and invasion through Wnt and epithelial-mesenchymal transition signaling pathways.

OBJECTIVE: Obesity is closely associated with metastasis in breast cancer patients. Secreted frizzled-related protein 5 (SFRP5), one of the novel adipokines with anti-inflammatory properties, is associated with obesity. This study aims to study the role of SFRP5 in the crosstalk between obesity and breast cancer metastasis and identify the underlying mechanism. METHODS: 3T3-L1 pre-adipocytes were differentiated to mature adipocytes and a hypertrophic adipocyte model was induced with palmitic acid (PA). Cell motility was measured in MDA-MB-231 and MCF-7 breast cancer cells co-cultured with adipocytes conditioned medium (CM) with or without SFRP5 protein. Wnt and epithelial-mesenchymal transition (EMT) signal pathways were investigated by western blot. Circulating SFRP5 level in 218 breast cancer patients and the association with clinicopathologic characteristics of breast cancer were further determined. Online databases ENCORI and PREDICT Plus were used to exam the link between SFRP5 and prognosis. RESULTS: Reduced SFRP5 level was detected in the hypertrophic adipocyte model. Recombinant SFRP5 protein inhibited MDA-MB-231 and MCF-7 cells invasion and migration induced by PA-treated adipocyte CM, and SFRP5 inhibition by specific antibody reversed the effect of SFRP5. Furthermore, SFRP5 significantly inhibited Wnt and downstream EMT in breast cancer cells. Low circulating SFRP5 level correlated with body mass index (BMI), lymph node (LN) metastasis, TNM stage and high Ki67 expression in breast cancer patients. Increased SFRP5 level was associated with favorable predicted survival. Kaplan-Meier curves showed high SFRP5 level in tumor tissue was associated with better outcome of breast cancer patients. CONCLUSIONS: Our findings demonstrated SFRP5 is a vital adipokine that mediates the crosslink between obesity and the metastatic potential of breast cancer. Promotion of SFRP5 expression in the adipose microenvironment may represent a novel approach for preventing breast cancer metastasis.

Erratum: Addendum: Metabolic Syndrome, and Particularly the Hypertriglyceridemic-Waist Phenotype, Increases Breast Cancer Risk, and Adiponectin Is a Potential Mechanism: A Case-Control Study in Chinese Women.

[This corrects the article DOI: 10.3389/fendo.2019.00905.].

Retraction Note: Effect of perioperative infusion of Dexmedetomidine combined with Sufentanil on quality of postoperative analgesia in patients undergoing laparoscopic nephrectomy: a CONSORT-prospective, randomized, controlled trial.

The authors have retracted this article.

Association of PTPN1 polymorphisms with breast cancer risk: A case-control study in Chinese females.

BACKGROUND: Breast cancer (BC) risk, development, and prognosis were closely related to obesity, diabetes mellitus, and metabolic syndrome. Protein tyrosine phosphatase, non-receptor type 1 (PTPN1) located on chromosome 20q13, could negatively regulate insulin and leptin signaling. In this study, we determined the association of PTPN1 polymorphisms with BC risk. METHODS: We analyzed the distribution of 11 selected PTPN1 single nucleotide polymorphisms in Chinese female patients with BC (n = 953) and healthy controls (n = 963) based on a multicenter case-control study. The association of PTPN1 genotypes and haplotypes frequencies with BC risk were determined by logistic regression analysis. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), diabetes mellitus history, and fasting plasma glucose level. The eQTL (expression Quantitative Trait Loci) analysis for PTPN1 was conducted by GTEx database. RESULTS: There were significant differences between BC cases and control groups in menopausal status, number of births, and BMI. Four single nucleotide polymorphisms (SNPs; rs3215684, rs3787345, rs718049, and rs718050) decreased overall BC risk, and other seven SNPs showed no significant association with BC risk. In multivariate analysis, BMI and rs3215684 DT + DD genotype were identified as independent risk factors for BC, and mutated genotypes of rs3215684 were correlated with increased PTPN1 expression. There are no haplotypes showed different frequencies between cases and controls. In the stratified analysis, rs2206656 showed a significant association with decreased BC risk in the subgroup of BMI ≤ 24 kg/m 2 , while rs3215684 and rs718049 showed lower BC risk in the subgroup of WHR > 0.85. Seven SNPs showed lower BC risk in the subgroup with diabetes mellitus history and/or fasting plasma glucose level ≥ 7 mM, while rs754118 decreased BC risk in the subgroup of fasting plasma glucose level < 7 mM. CONCLUSION: Our findings suggest that PTPN1 SNPs associated with BC susceptibility in Chinese females, which also suggested a novel mechanism between obesity, diabetes mellitus, and BC risk.

Metabolic Syndrome, and Particularly the Hypertriglyceridemic-Waist Phenotype, Increases Breast Cancer Risk, and Adiponectin Is a Potential Mechanism: A Case-Control Study in Chinese Women.

Objective: To investigate the association between metabolic syndrome and breast cancer and to elucidate the potential mechanism underlying this association. Patients and Methods: Based on baseline data drawn from 21 hospitals in 11 provinces of China, we performed a case-control study among 1,127 women (595 cases and 532 controls), divided into premenopausal, and postmenopausal subgroups. Student's t test, Pearson's χ2 test, and logistic regression analyses were performed to ascertain the association between breast cancer and metabolic syndrome, including all of its components. In addition, we attempted to clarify the potential role of adiponectin in this association. Results: Among the components of metabolic syndrome, abnormal waist circumference was the component that markedly increased breast cancer risk in premenopausal women (OR 1.447, 95% CI 1.043-2.006). Metabolic syndrome with clusters of special risk factors showed an association with breast cancer risk. Among all these components of metabolic syndrome, the hypertriglyceridemic-waist (HW) phenotype significantly increased breast cancer risk (OR 1.56, 95% CI 1.02-2.39), regardless of menopausal status, rendering it a strong predictor of breast cancer. Total adiponectin levels and high-molecular-weight adiponectin were reversely associated with metabolic syndrome. In addition, total adiponectin levels among breast cancer patients were much lower than among controls (6.67 ± 3.05 vs. 8.01 ± 4.18, p = 0.014) only in the HW phenotype subgroup. Furthermore, the HW phenotype was associated with increased risk of estrogen receptor/progesterone receptor-positive (ER+/PR+) and -negative (ER-/PR-) breast cancer, with a 51% (OR 1.51, 95% CI 1.03-2.21) and 69% (OR 1.69, 95% CI 1.05-2.72) increase, respectively. However, there was no significant association between the HW phenotype and the ER+/PR- subtype. These results suggested that low adiponectin levels may be a mechanism that explains the association between the HW phenotype and breast cancer risk. Conclusion: Metabolic syndrome with special cluster factors is related to breast cancer risk; in particular, the HW phenotype can be regarded as a strong predictor of breast cancer. As an important factor involved in fat metabolism, adiponectin may strongly predict metabolic syndrome, especially the HW phenotype and breast cancer. Further research into this mechanism and epidemiological studies are needed. This study provides new evidence for the role of a healthy lifestyle in preventing breast cancer.

Effect of perioperative infusion of Dexmedetomidine combined with Sufentanil on quality of postoperative analgesia in patients undergoing laparoscopic nephrectomy: a CONSORT-prospective, randomized, controlled trial.

BACKGROUND: Postoperative pain is one of the most common symptoms after surgery, which brings physical discomfort to patients. In addition, it may cause a series of complications, and even affect the long-term quality of life. The purpose of this prospective, randomized, double-blinded, controlled trial is to investigate the efficacy and safety of dexmedetomidine combined with sufentanil to attenuate postoperative pain in patients after laparoscopic nephrectomy. METHODS: Ninety patients undergoing laparoscopic nephrectomy were randomized into three groups: the control (sufentanil 0.02 µg/kg/h, Group C), sufentanil plus low dose of dexmedetomidine (0.02 µg/kg/h each, Group D1), and sufentanil plus high dose of dexmedetomidine (0.04 µg/kg/h, Group D2). The patient-controlled analgesia was programmed to deliver a bolus dose of 0.5 ml, followed by an infusion of 2 ml/h and a lockout time of 10 min. The primary goal was to calculate the cumulative amount of self-administered sufentanil; the secondary goals were to estimate pain intensity using the numerical rating scale (NRS), level of sedation, the first bowel movement, concerning adverse effects as well as duration of postoperative hospital stay. RESULTS: The total consumption of sufentanil in group D1 and D2 were significantly lower than in group C during the first 8 h after surgery (P < 0.05), whereas there were no statistically significant differences (P > 0.05) between group D1 and D2. Compared with group C, the NRS scores at rest during first 8 h after surgery were significantly lower in group D1 (P < 0.05). The NRS scores, neither at rest nor with movement, show statistically significant differences between group D1 and D2 at each time point following surgery (P > 0.05). The time to first flatus was shorter in group D1 compared with the control group (P < 0.05). In addition, compared with group C, group D1 and D2 had a shorter time for first defecation (P < 0.05). CONCLUSIONS: Dexmedetomidine combined with sufentanil showed better postoperative analgesia without adverse effects, as well as facilitated bowel movements for patients undergoing laparoscopic nephrectomy. TRIAL REGISTRATION: We registered this study in a Chinese Clinical Trial Registry (ChiCTR) centre on Dec 23 2015 and received the registration number: ChiCTR-IPR-15007628 .

Impact of phosphorylated insulin-like growth factor-1 receptor on the outcome of breast cancer patients and the prognostic value of its alteration during neoadjuvant chemotherapy.

The expression of insulin-like growth factor-1 receptor (IGF-1R), which is involved in the genesis and progression of breast cancer, is thought to be associated with the overall survival (OS) of patients. However, the predictive and prognostic significance of the IGF-1R expression in breast cancer remains controversial. The present study aimed to identify the factors associated with the levels of phosphorylated (p)-IGF-1R in breast cancer, their impact on the outcomes of breast cancer patients, and the prognostic value of alterations of p-IGF-1R during neoadjuvant chemotherapy (NAC). The present study included 348 female breast cancer patients whose paraffin-embedded tumor tissue sections had been collected by biopsy and/or resection, among which the pre-NAC and post-NAC sections were available from 40 patients. Human epidermal growth factor receptor 2 (HER2) positivity and molecular subtype were significantly associated with the presence of p-IGF-1R in the tumor tissue (P<0.05). Patients with p-IGF-1R present in the tumor tissue had a shorter OS (P=0.003). The p-IGF-1R levels in the tumor after NAC differed significantly from those prior to NAC (P=0.005); however, this alteration in p-IGF-1R levels was not associated with a shorter OS. In parallel with HER2, p-IGF-1R appears to be a promising indicator for predicting clinical outcomes and may be an attractive target for improving the efficacy of antitumor therapy, particularly for patients with HER2-negative, estrogen receptor-positive and luminal B tumors.

A case-control study on risk factors of breast cancer in Han Chinese women.

This study aimed to investigate risk factors associated with breast cancer among Han Chinese women in northern and eastern China. A matched case-control study involving 1489 patients with breast cancer and 1489 controls was conducted across 21 hospitals in 11 provinces in China, from April 2012 to April 2013. We developed a structured questionnaire to record information from face-to-face interviews with participants. Student's t-tests, Pearson's chi-square tests, and univariate and multivariate conditional logistic regression analyses were used to identify variables with significant differences between the case and control groups. Ten variables were identified (P<0.05): location, economic status, waist-to-hip ratio, menopause, family history of breast cancer, present life satisfaction, sleep satisfaction, milk products, behavior prevention scores, and awareness of breast cancer. We identified a comprehensive range of factors related to breast cancer, among which several manageable factors may contribute to breast cancer prevention. Further prospective studies concerning psychological interventions, sleep regulation, health guidance, and physical exercise are required. A screening model for high-risk populations should be put on the agenda.

Circulating High-Molecular-Weight (HMW) Adiponectin Level Is Related with Breast Cancer Risk Better than Total Adiponectin: A Case-Control Study.

The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI<=24.0. Higher HMW/total adiponectin ratio was negatively associated with breast cancer (P=0.019) in the subgroup of postmenopausal women. Interestingly, in the subgroup of women with family history of breast cancer, higher circulating total and HMW adiponectin were positively associated with breast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed.

Screening for candidate genes related to breast cancer with cDNA microarray analysis.

OBJECTIVE: The aim of this study was to reveal the exact changes during the occurrence of breast cancer to explore significant new and promising genes or factors related to this disease. METHODS: We compared the gene expression profiles of breast cancer tissues with its uninvolved normal breast tissues as controls using the cDNA microarray analysis in seven breast cancer patients. Further, one representative gene, named IFI30, was quantitatively analyzed by real-time PCR to confirm the result of the cDNA microarray analysis. RESULTS: A total of 427 genes were identified with significantly differential expression, 221 genes were up-regulated and 206 genes were down-regulated. And the result of cDNA microarray analysis was validated by detection of IFI30 mRNA level changes by real-time PCR. Genes for cell proliferation, cell cycle, cell division, mitosis, apoptosis, and immune response were enriched in the up-regulated genes, while genes for cell adhesion, proteolysis, and transport were significantly enriched in the down-regulated genes in breast cancer tissues compared with normal breast tissues by a gene ontology analysis. CONCLUSION: Our present study revealed a range of differentially expressed genes between breast cancer tissues and normal breast tissues, and provide candidate genes for further study focusing on the pathogenesis and new biomarkers for breast cancer.

Spatial location engineering of oxygen vacancies for optimized photocatalytic H2 evolution activity.

Enhanced H2 evolution efficiency is achieved via manipulating the spatial location of oxygen vacancies in niobates. The ultrathin K4 Nb6O17 nanosheets which are rich in surface oxygen vacancies show enhanced optical absorption and band gap narrowing. Meanwhile, the fast charge separation effectively reduces the probability of hole-electron recombination, enabling 20 times hydrogen evolution rate compared with the defect-free bulk counterpart.