A flexible and stretchable triboelectric nanogenerator based on a medical conductive hydrogel for biomechanical energy harvesting and electronic switches.

With the development of intelligent wearable electronic products, new requirements are put forward for large-scale production and durable power supplies and sensors. Herein, a flexible and stretchable single-electrode triboelectric nanogenerator (TENG) based on a medical conductive hydrogel (MCH) has been fabricated for biomechanical energy harvesting and electronic switches. The obtained MCH-TENG encapsulated by silicone rubber as an electrification layer demonstrated high electrical output performances. The size of the fabricated MCH-TENG was 40 × 60 mm2, which can generate an open-circuit voltage of 400 V, a power density of 444.44 mW m-2, and power 240 LEDs in series at a contact frequency of 3.0 Hz. The device can act not only as a power supply to drive electronic devices, but also as an energy collector to collect the energy of human movements. Particularly, as an electronic switch, the device enabled a high current amplification through the Darlington transistor circuit. Consequently, this work provides a new perspective of flexible and stretchable MCH-TENGs for wearable electronic devices.

Circulating cell-free DNA-based methylation patterns for breast cancer diagnosis.

Mammography is used to detect breast cancer (BC), but its sensitivity is limited, especially for dense breasts. Circulating cell-free DNA (cfDNA) methylation tests is expected to compensate for the deficiency of mammography. We derived a specific panel of markers based on computational analysis of the DNA methylation profiles from The Cancer Genome Atlas (TCGA). Through training (n = 160) and validation set (n = 69), we developed a diagnostic prediction model with 26 markers, which yielded a sensitivity of 89.37% and a specificity of 100% for differentiating malignant disease from normal lesions [AUROC = 0.9816 (95% CI: 96.09-100%), and AUPRC = 0.9704 (95% CI: 94.54-99.46%)]. A simplified 4-marker model including cg23035715, cg16304215, cg20072171, and cg21501525 had a similar diagnostic power [AUROC = 0.9796 (95% CI: 95.56-100%), and AUPRC = 0.9220 (95% CI: 91.02-94.37%)]. We found that a single cfDNA methylation marker, cg23035715, has a high diagnostic power [AUROC = 0.9395 (95% CI: 89.72-99.27%), and AUPRC = 0.9111 (95% CI: 88.45-93.76%)], with a sensitivity of 84.90% and a specificity of 93.88%. In an independent testing dataset (n = 104), the obtained diagnostic prediction model discriminated BC patients from normal controls with high accuracy [AUROC = 0.9449 (95% CI: 90.07-98.91%), and AUPRC = 0.8640 (95% CI: 82.82-89.98%)]. We compared the diagnostic power of cfDNA methylation and mammography. Our model yielded a sensitivity of 94.79% (95% CI: 78.72-97.87%) and a specificity of 98.70% (95% CI: 86.36-100%) for differentiating malignant disease from normal lesions [AUROC = 0.9815 (95% CI: 96.75-99.55%), and AUPRC = 0.9800 (95% CI: 96.6-99.4%)], with better diagnostic power and had better diagnostic power than that of using mammography [AUROC = 0.9315 (95% CI: 89.95-96.34%), and AUPRC = 0.9490 (95% CI: 91.7-98.1%)]. In addition, hypermethylation profiling provided insights into lymph node metastasis stratifications (p < 0.05). In conclusion, we developed and tested a cfDNA methylation model for BC diagnosis with better performance than mammography.

Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer.

Objective: Triple negative breast cancer (TNBC) is known to have aggressive clinical course and a high risk of recurrence. Given the lack of effective targeted therapy options, paclitaxel-based chemotherapy is still the primary option for TNBC patients. However, patients who fail to achieve a complete response during neoadjuvant chemotherapy may be mainly due to sensitivity and resistance to chemotherapy. Thus, we concentrated the present research on the role of PGK1 in the sensitivity to paclitaxel treatment and the possible underlying mechanisms in TNBC. Methods: After exposure to paclitaxel, a cell viability analysis was made to investigate the influence of PGK1 silencing on cell death. The effect of PGK1 on apoptosis induced by paclitaxel treatment was examined in vitro by flow cytometry cell apoptosis assays. Western blotting was performed to examine the impact of PGK1 on paclitaxel-induced apoptosis. The correlation of PGK1 with apoptosis-associated protein X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) was analyzed in 39 specimens by immunohistochemistry analysis. Results: We observed that silencing PGK1 sensitized triple-negative breast cancer (TNBC) cell lines to paclitaxel treatment as a result of increased drug-induced apoptosis. Furthermore, mechanistic investigations suggested that XAF1 was increased in PGK1-knockdown cells along with the expression of the apoptotic proteins including cleaved caspase-3 and Bax. Immunohistochemistry analysis showed that PGK1 was negatively related to XAF1. Moreover, we found that downregulation of XAF1 reduced paclitaxel-induced apoptosis in PGK1-silenced triple-negative cell lines. Conclusion: Our results identified PGK1 as a potential biomarker for the treatment of TNBC, and inhibition of PGK1 expression might represent a novel strategy to sensitize TNBC to paclitaxel treatment.

Hypoxia-Mediated Complement 1q Binding Protein Regulates Metastasis and Chemoresistance in Triple-Negative Breast Cancer and Modulates the PKC-NF-κB-VCAM-1 Signaling Pathway.

OBJECTIVES: Complement 1q binding protein (C1QBP/HABP1/p32/gC1qR) has been found to be overexpressed in triple-negative breast cancer (TNBC). However, the underlying mechanisms of high C1QBP expression and its role in TNBC remain largely unclear. Hypoxia is a tumor-associated microenvironment that promotes metastasis and paclitaxel (PTX) chemoresistance in tumor cells. In this study, we aimed to assess C1QBP expression and explore its role in hypoxia-related metastasis and chemoresistance in TNBC. MATERIALS AND METHODS: RNA-sequencing of TNBC cells under hypoxia was performed to identify C1QBP. The effect of hypoxia inducible factor 1 subunit alpha (HIF-1α) on C1QBP expression was investigated using chromatin immunoprecipitation (ChIP) assay. The role of C1QBP in mediating metastasis, chemoresistance to PTX, and regulation of metastasis-linked vascular cell adhesion molecule 1 (VCAM-1) expression were studied using in vitro and in vivo experiments. Clinical tissue microarrays were used to verify the correlation of C1QBP with the expression of HIF-1α, VCAM-1, and RELA proto-oncogene nuclear factor-kappa B subunit (P65). RESULTS: We found that hypoxia-induced HIF-1α upregulated C1QBP. The inhibition of C1QBP notably blocked metastasis of TNBC cells and increased their sensitivity to PTX under hypoxic conditions. Depletion of C1QBP decreased VCAM-1 expression by reducing the amount of P65 in the nucleus and suppressed the activation of hypoxia-induced protein kinase C-nuclear factor-kappa B (PKC-NF-κB) signaling.immunohistochemistry (IHC) staining of the tissue microarray showed positive correlations between the C1QBP level and those of HIF-1α, P65, and VCAM-1. CONCLUSION: Targeting C1QBP along with PTX treatment might be a potential treatment for TNBC patients.

Fibroblast growth factor receptor 4 as a prognostic indicator in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) constitutes up to 15% of all breast cancers. It is one of the most aggressive breast cancers and is more prone to metastasize compared with other subtypes. Breast cancer patients with this subtype usually have a poor prognosis. Fibroblast growth factor receptor 4 (FGFR4) belongs to the receptor tyrosine kinase (RTK) family, and early analyses identified that FGFR4 was involved in breast cancer. However, the prognostic effect of FGFR4 on TNBC is unknown. In the present study, we investigated the association between FGFR4 and TNBC prognosis. METHODS: A total of 282 TNBC patients were enrolled. FGFR4 protein expression was detected in these 282 TNBC patients using immunohistochemistry (IHC). RESULTS: In the present study, FGFR4 was highly expressed in TNBC patients. Lymph node metastasis (LNM) (P=0.033) and p53 status (P=0.019) were associated with high FGFR4 expression. Univariate analysis identified high FGFR4 expression (P=0.016) as a prognostic predictor, and multivariate analysis found that high FGFR4 expression (P=0.016) was an independent prognostic factor. The Kaplan-Meier survival curve showed that high FGFR4 protein expression was correlated with poorer overall survival (OS). CONCLUSIONS: The results of our present study show that FGFR4 protein expression is correlated with a worse prognosis in TNBC.

Parallel Analyses of Somatic Mutations in Plasma Circulating Tumor DNA (ctDNA) and Matched Tumor Tissues in Early-Stage Breast Cancer.

PURPOSE: Early detection and intervention can decrease the mortality of breast cancer significantly. Assessments of genetic/genomic variants in circulating tumor DNA (ctDNA) have generated great enthusiasm for their potential application as clinically actionable biomarkers in the management of early-stage breast cancer.Experimental Design: In this study, 861 serial plasma and matched tissue specimens from 102 patients with early-stage breast cancer who need chemotherapy and 50 individuals with benign breast tumors were deeply sequenced via next-generation sequencing (NGS) techniques using large gene panels. RESULTS: Cancer tissues in this cohort of patients showed profound intratumor heterogeneities (ITHGs) that were properly reflected by ctDNA testing. Integrating the ctDNA detection rate of 74.2% in this cohort with the corresponding predictive results based on Breast Imaging Reporting and Data System classification (BI-RADS) could increase the positive predictive value up to 92% and potentially dramatically reduce surgical overtreatment. Patients with positive ctDNA after surgery showed a higher percentage of lymph node metastasis, indicating potential recurrence and remote metastasis. The ctDNA-positive rates were significantly decreased after chemotherapy in basal-like and Her2+ tumor subtypes, but were persistent despite chemotherapy in luminal type. The tumor mutation burden in blood (bTMB) assessed on the basis of ctDNA testing was positively correlated with the TMB in tumor tissues (tTMB), providing a candidate biomarker warranting further study of its potentials used for precise immunotherapy in cancer. CONCLUSIONS: These data showed that ctDNA evaluation is a feasible, sensitive, and specific biomarker for diagnosis and differential diagnosis of patients with early-stage breast cancer who need chemotherapy.

Effects of FGFR1 Gene Polymorphisms on the Risk of Breast Cancer and FGFR1 Protein Expression.

BACKGROUND/AIMS: Fibroblast growth factor receptor 1 (FGFR1) is widely considered to play an important role in mammary carcinogenesis. Some common variants in FGFR1 might be associated with its expression, and further affect breast cancer risk. The aim of this study was to investigate effects of single-nucleotide polymorphisms (SNPs) in FGFR1 on breast cancer susceptibility and FGFR1 protein expression. METHODS: SNPs rs17182023, rs17175624 and rs10958704 in FGFR1 were genotyped in 747 breast cancer cases and 716 healthy controls by SNaPshot method. The associations between SNPs and breast cancer were examined by logistic regression. Immunohistochemistry(IHC) was used to detect FGFR1 protein expression, and the association of FGFR1 polymorphisms with its protein expression was analyzed by Pearson's chi-square test. Additionally, Cox regression and Kaplan-Meier analysis was used to evaluate the association between FGFR1 protein expression and breast cancer prognosis. RESULTS: The minor allele of rs17182023 in FGFR1 was significantly associated with reduced breast cancer risk, with an odds ratio of 0.800 (95%CI = 0.684-0.935). No significant associations were detected between other SNPs and breast cancer. Moreover, rs17182023 was correlated to FGFR1 protein expression (P = 0.006), and patients with high FGFR1 protein expression tended to have poor outcomes. CONCLUSIONS: SNP rs17182023 was correlated to reduced breast cancer risk, and was associated with FGFR1 protein expression. High FGFR1 protein expression was an independent risk factor of breast cancer, and resulted in poor prognosis.

Prognostic implications of fibroblast growth factor receptor 4 polymorphisms in primary breast cancer.

Fibroblast growth factor receptor 4 (FGFR4) belongs to the receptor tyrosine kinase (RTK) family, and FGFR4 polymorphisms have been implicated in both normal development and cancer, including breast cancer. In the present study, we investigated correlations between polymorphisms in FGFR4 and breast cancer prognosis. The FGFR4 SNPs rs1966265 and rs351855 were genotyped in 747 breast cancer patients using the SNaPshot method. FGFR4 protein expression was detected by immunohistochemistry in 339 samples. SNP rs351855 was correlated with FGFR4 protein expression under dominant and co-dominant models. Lymph node metastasis (LNM), ER (estrogen receptor) status, and molecular subtype were associated with high FGFR4 expression. Univariate analysis revealed rs351855 (CC/CT: P = 0.027, CC/TT: P < 0.001, CC/CT + TT: P = 0.005) to be a prognostic predictor, and multivariate analysis indicated rs351855 (CC/TT: P = 0.005) to be an independent prognostic factor. Kaplan-Meier survival analysis showed that high FGFR4 protein expression was associated with a poor prognosis. SNP rs351855 was correlated with worse outcomes, with a dose-dependent effect. The results of this study show that FGFR4 SNP rs351855 is associated with up-regulation of FGFR4 protein expression and a worse prognosis in breast cancer.

Androgen Receptor Expression and Bicalutamide Antagonize Androgen Receptor Inhibit ß-Catenin Transcription Complex in Estrogen Receptor-Negative Breast Cancer.

BACKGROUND/AIMS: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment. METHODS: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer. RESULTS: AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/ß-catenin signaling and inhibited the growth of AR+/ER- breast cancer. CONCLUSION: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.

The associations of genetic polymorphisms in CYP1A2 and CYP3A4 with clinical outcomes of breast cancer patients in northern China.

BACKGROUND: Cytochrome P450 (CYP) 1A2 and CYP3A4 may play a role in the differentiation of clinical outcomes among breast cancer women. This study aimed to analyze the association of genetic polymorphisms in the CYP1A2 and CYP3A4 genes with clinicopathological features, protein expression and prognosis of breast cancer in the northern Chinese population. RESULTS: Firstly, SNP rs11636419, rs17861162 and rs2470890 in the CYP1A2 were significantly associated with age and menstruation status. And SNP rs11636419 and rs17861162 were associated with the P53 status. Secondly, SNP rs2470890 was correlated with CYP1A2 protein expression under the co-dominant and dominant model (P = 0.017, P = 0.006, respectively). Thirdly, for SNP rs2470890, the Kaplan-Meier 5 year survival curves showed that patients carrying genotypes CT or TT had a worse OS compared with the genotype CC carriers under both codominant and dominant model (P < 0.001, P < 0.001, respectively). MATERIALS AND METHODS: Four single nucleotide polymorphisms (SNPs) were successfully genotyped in 459 breast cancer patients using the SNaPshot method. The associations of four polymorphisms with protein expression and clinicopathological characteristics were evaluated by Pearson's chi-square test. The Cox hazard regression analysis and Kaplan-Meier survival analysis were performed to evaluate the relationship between the SNPs and overall survival (OS) of breast cancer. CONCLUSIONS: CYP1A2 rs2470890 was significantly associated with the prognosis of patients with breast cancer and could serve as an independent impact factor of prognosis of breast carcinoma.

A novel panel of serum miR-21/miR-155/miR-365 as a potential diagnostic biomarker for breast cancer.

PURPOSE: Insufficient sensitivity and specificity prevent the use of most existing biomarkers for early detection of breast cancer. Recently, it was reported that serum microRNAs (miRNAs) may be potential biomarkers in many cancer diseases. In this study, we investigated whether serum levels of 5 miRNAs including miR-21, miR-125b, miR-145, miR-155, and miR-365 could discriminate breast cancer patients and healthy controls. METHODS: Serum levels of miRNAs were measured by using quantitative real-time polymerase chain reaction in 99 breast cancer patients and 21 healthy controls. The abundance change of serum miRNAs were also evaluated following surgical resection in 20 breast cancer patients. Receiver operating characteristic (ROC) curve analysis was performed to assess the sensitivity and specificity of miRNAs as diagnostic biomarkers. RESULTS: Serum levels of miR-21 and miR-155 was significantly higher, while miR-365 was significantly lower in breast cancer as compared with healthy controls. The serum levels of miR-21 and miR-155 significantly decreased following surgical resection. Additionally, the serum level of miR-155 at stages I and II was significantly higher compared to stage III. The serum miR-145 level was remarkably higher in progesterone receptor (PR)-positive patients than PR-negative. The positivity of miR-21, miR-155, and miR-365 was high compared to CA 153 and CEA in breast cancer. ROC curve analyses of a combination of miR-21, miR-155, and miR-365 yielded much higher area under curve and enhanced sensitivity and specificity in comparison to each miRNA alone. CONCLUSION: The combination of serum miR-21/miR-155/miR-365 may potentially serve as a sensitive and specific biomarker that enables differentiation of breast cancer from healthy controls.

Increased breast cancer risk with HABP1/p32/gC1qR genetic polymorphism rs2285747 and its upregulation in northern Chinese women.

OBJECT: Hyaluronic acid binding protein 1 (HABP1/p32/gC1qR) is overexpressed in breast cancer. However, it is unknown whether HABP1 gene polymorphisms affect breast cancer risk. This study aims to evaluate the potential association of single nucleotide polymorphisms (SNPs) of HABP1 with breast cancer in northern Chinese women. RESULTS: The minor allele of rs2285747 was strongly associated with breast cancer with OR of 1.553 (95% CI = 1.251-1.927). SNP rs2285747 was also associated with high HABP1 protein expression under the co-dominant and dominant model (p = 0.005, p = 0.019, respectively). For rs2472614, the patients with CG and GG were more likely to have HER2 negative tumors compared to CC (p = 0.015). For rs3786054, the patients with AG and GG were more likely to have HER2 and P53 negative breast cancer compared to AA (p = 0.024, p = 0.064, receptively). MATERIALS AND METHODS: Seven SNPs were analyzed in 505 breast cancer patients and 505 controls using SNaPshot method. The associations between SNPs and breast cancer were examined by logistic regression. The associations of SNPs with HABP1 protein expression and disease characteristics were examined by chi-square test. CONCLUSIONS: SNP rs2285747 of HABP1 increased breast cancer risk and elevated its protein expression in northern Chinese women.

Association of FGFR3 and FGFR4 gene polymorphisms with breast cancer in Chinese women of Heilongjiang province.

BACKGROUND: The fibroblast growth factor (FGF) receptor pathway is activated in many tumors. FGFR2 has been identified as a breast cancer susceptibility gene. Common variation in other FGF receptors might also affect breast cancer risk. We carried out a case-control study to investigate associations of variants in FGFR3 and FGFR4 with breast cancer in women from Heilongjiang Province. METHODS: SNP rs2234909 and rs3135848 in FGFR3 and rs1966265 and rs351855 in FGFR4 were successfully genotyped in 747 breast cancer patients and 716 healthy controls using the SNaPshot method. The associations between SNPs and breast cancer were examined by logistic regression. The associations between SNPs and disease characteristics were examined by chi-square tests or one-way ANOVA as needed. RESULTS: The minor alleles of rs1966265 and rs351855 in FGFR4 were strongly associated with breast cancer in the population, with odds ratios of 1.335 (95%CI = 1.154-1.545) and 1.364 (95%CI = 1.177-1.580), respectively. However, no significant associations were detected between other SNPs and breast cancer. Analyses of the disease characteristics showed that SNP rs351855 was associated with lymph-node-positive breast cancer with a dose-dependent effect of the minor allele (P = 0.008). CONCLUSIONS: SNPs rs1966265 and rs351855 in FGFR4 were associated with breast cancer in a northern Chinese population.

Effects of HER2 genetic polymorphisms on its protein expression in breast cancer.

BACKGROUND AND PURPOSES: HER2 protein expression has been considered to be an important prognostic factor in breast cancer patients. Although the molecular mechanism of HER2 protein expression is currently unknown, single nucleotide polymorphisms (SNPs) of the HER2 gene may have some effects on its own expression. Here, we performed a trial to study the association between HER2 genetic polymorphisms and its protein expression in breast cancer. METHODS: Three SNPs in the HER2 gene were genotyped in 303 breast cancer patients using the Sequenom Mass ARRAY system. HER2 protein expression, ER, PR, P53, and Ki67 status was detected by immunohistochemistry. A Pearson's chi-square test was used to analyze the associations of the polymorphisms with its protein expression, corresponding with clinicopathological characteristics of breast cancer. RESULTS: Under the codominant model, rs1058808 and rs2517956 polymorphisms were associated with HER2 protein expression in breast cancer (p=0.007; p=0.008, respectively). For SNP rs1058808, patients with genotypes CG and GG were more likely to have high HER2 protein expression than patients with genotype CC (p=0.007). No significant associations could be found between the three SNPs and breast cancer patients' clinical stage, tumor size, histological grade, lymph node metastasis, ER, PR, Ki67 and P53 status (p>0.05). CONCLUSIONS: HER2 rs1058808 and rs2517956 polymorphisms are associated with its protein expression in breast cancer. Our study might provide new insights into the mechanisms of HER2 protein expression.

Association between single nucleotide polymorphisms in the OPRM1 gene and intraoperative remifentanil consumption in northern Chinese women.

BACKGROUND: Recent studies have suggested that some single nucleotide polymorphisms (SNPs) in the human µ-opioid receptor gene (OPRM1) affect the postoperative analgesic efficacy of opioids and their side effects. In this study, we assessed the association between SNPs in the OPRM1 gene and intraoperative remifentanil consumption as well as perioperative side effects during gynecological hysteroscopic surgery in women from Northern China. METHODS: We analyzed 178 women undergoing gynecological hysteroscopic surgery. SNP genotyping was performed using the SNaPshot method. The state anxiety index (SAI) and pressure pain threshold (PPT) of all patients were assessed preoperatively. Monitored anesthesia care was maintained by the intravenous infusion of remifentanil. Intraoperative remifentanil usage and perioperative side effects were recorded. Statistical analyses were performed using SPSS software. RESULTS: Patients carrying one or two copies of the minor allele (G allele) of rs558025 required significantly more intraoperative remifentanil than patients without the minor allele (p = 0.001, corrected p = 0.006). There were no significant associations between the six SNPs and various clinical characteristics. No significant associations between the six SNPs and PPT or SAI were found in our study. CONCLUSIONS: SNP rs558025 in the OPRM1 gene was associated with intraoperative remifentanil consumption during gynecological hysteroscopic surgery in our subjects.

Superomniphobic, transparent, and antireflection surfaces based on hierarchical nanostructures.

Optical surfaces that can repel both water and oil have much potential for applications in a diverse array of technologies including self-cleaning solar panels, anti-icing windows and windshields for automobiles and aircrafts, low-drag surfaces, and antismudge touch screens. By exploiting a hierarchical geometry made of two-tier nanostructures, primary nanopillars of length scale ∼ 100-200 nm superposed with secondary branching nanostructures made of nanoparticles of length scale ∼ 10-30 nm, we have achieved static contact angles of more than 170° and 160° for water and oil, respectively, while the sliding angles were lower than 4°. At the same time, with respect to the initial flat bare glass, the nanotextured surface presented significantly reduced reflection (<0.5%), increased transmission (93.8% average over the 400 to 700 nm wavelength range), and very low scattering values (about 1% haze). To the authors' knowledge, these are the highest optical performances in conjunction with superomniphobicity reported to date in the literature. The primary nanopillars are monolithically integrated in the glass surface using lithography-free metal dewetting followed by reactive ion etching,1 while the smaller and higher surface area branching structure made of secondary nanoparticles are deposited by the NanoSpray2 combustion chemical vapor deposition (CCVD).

Associations between single-nucleotide polymorphisms and epidural ropivacaine consumption in patients undergoing breast cancer surgery.

Up to date, few published studies indicated the associations between genetic polymorphisms and epidural local anesthetics consumption. In this study, we investigated the associations between seven single-nucleotide polymorphisms (SNPs) and epidural ropivacaine consumption during breast cancer surgery in women from northeastern China. These seven SNPs (rs3803662 and rs12443621 in TNCR9, rs889312 in MAP3K1, rs3817198 in LSP1, rs13387042 at 2q35, rs13281615 at 8q24, and rs2046210 at 6q25.1) were identified by recent genome-wide association studies associated with tumor susceptibility. A total of 418 breast cancer women received thoracic epidural anesthesia with ropivacaine for elective mastectomy with axillary clearance. Their blood samples were genotyped for the seven SNPs using the SNaPshot method. For SNP rs13281615, the subjects with genotype AG and GG consumed a greater amount of the total epidural ropivacaine and the mean ropivacaine dose than the subjects with genotype AA (p=0.047 and p=0.003, respectively). Furthermore, no statistical differences were found in the total dose of ropivacaine, the mean consumption of ropivacaine, the onset of ropivacaine, or the initial dose of lidocaine among the three genotypic groups for the other six SNPs studied. Our study indicated that SNP rs13281615 at 8q24 was associated with the consumption of epidural ropivacaine during breast cancer surgery in northeastern Chinese women. It might provide new insights into the mechanisms of ropivacaine action and metabolism and facilitate the development of personalized medicine.

One new antitumour cassane-type diterpene from Caesalpinia crista.

1α-acetoxy-5α, 7ß-dihydroxycassa-11,13(15)-diene-16,12-lactone, a new cassane-type diterpene was isolated from Caesalpinia crista. The structure of this compound was elucidated by analysis of NMR spectra, and the relative configuration was established by NOE experiment. The new compound was evaluated for antitumour activity against T47D, DU145 and showed significant inhibitory activities.

A miRNA binding site single-nucleotide polymorphism in the 3'-UTR region of the IL23R gene is associated with breast cancer.

BACKGROUND: Research into the etiology of breast cancer has recently focused on the role of the immunity and inflammation. Interleukin-23 and its receptor (IL23R) guide T cells towards the Th17 phenotype. IL23R single nucleotide polymorphisms (SNPs) have been shown to be associated with digestive system cancers. To evaluate the influences of IL23R gene polymorphisms on the risk of sporadic breast cancer, a case-control study was conducted in Chinese Han women. METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped two tag SNPs (rs10889677 in the 3'-UTR region and nonsynonymous variants rs1884444 in exon 2) in IL23R gene of 491 breast cancer patients and 502 matched healthy controls. The genotypes were determined using the SNaPshot technique. The differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed with the Chi-square test for trends. For rs10889677 in IL23R, the frequencies of the AA genotype and the A allele were statistical significant higher in breast cancer patients than in controls (P = 0.0084 and P = 0.0171, respectively), whereas the C allele was associated with an earlier age of breast cancer onset (50.6 years for AA, 48.7 years for AC and 46.0 years for CC (P = 0.0114)) in case-only study. The clinical features analysis demonstrated significant associations between rs1884444 in IL23R and human epidermal growth factor receptor 2 (Her-2) and tumor size status. CONCLUSIONS AND SIGNIFICANCE: Our results suggest that a miRNA binding site SNP in the 3'-UTR region of the IL23R gene may be associated with the risk of breast cancer and contribute to the early development of breast cancer in Chinese women.

Association analysis of IL-17A and IL-17F polymorphisms in Chinese Han women with breast cancer.

BACKGROUND: Research into the etiology of breast cancer has recently focused on the role of the immunity and inflammation. The proinflammatory cytokines IL-17A and IL-17F can mediate inflammation and cancer. To evaluate the influences of IL-17A and IL-17F gene polymorphisms on the risk of sporadic breast cancer, a case-control study was conducted in Chinese Han women. METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped three single-nucleotide polymorphisms (SNPs) in IL-17A (rs2275913, rs3819025 and rs3748067) and five SNPs in IL-17F (rs7771511, rs9382084, rs12203582, rs1266828 and rs763780) to determine the haplotypes in 491 women with breast cancer and 502 healthy individuals. The genotypes were determined using the SNaPshot technique. The differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed with the Chi-square test for trends. For rs2275913 in IL-17A, the frequency of the AA genotype was higher in patients than controls (P = 0.0016). The clinical features analysis demonstrated significant associations between IL-17 SNPs and tumor protein 53 (P53), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and triple-negative (ER-/PR-/Her-2-) status. In addition, the haplotype analysis indicated that the frequency of the haplotype A(rs2275913)G(rs3819025)G(rs3748067), located in the IL-17A linkage disequilibrium (LD) block, was higher in patients than in controls (P = 0.0471 after correction for multiple testing). CONCLUSIONS AND SIGNIFICANCE: Our results suggested that SNPs in IL-17A but not IL-17F were associated with the risk of breast cancer. Both IL-17A and IL-17F gene polymorphisms may provide valuable information for predicting the prognosis of breast cancer in Chinese women.