FUS-Mediated CircFGFR1 Accelerates the Development of Papillary Thyroid Carcinoma by Stabilizing FGFR1 Protein.

Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer and its incidence is rising globally. The molecular mechanisms of PTC progression remain unclear, hindering the development of effective treatments. This study focuses on hsa_circ_0008016 (circFGFR1), a circular RNA significantly up-regulated in PTC cells. Silencing circFGFR1 inhibited PTC cell proliferation and increased cell apoptosis, suggesting its role in PTC progression. The RNA-binding protein FUS was identified as a promoter of circFGFR1 formation. While circFGFR1 does not influence FGFR1 mRNA translation, it inhibits ubiquitination and degradation of FGFR1 protein, prolonging its half-life. CircFGFR1 also interacts with protein CBL, inhibiting CBL-mediated ubiquitination of FGFR1 proteins. Rescue assays confirmed circFGFR1 promotes PTC cell growth through mediating FGFR1. This study highlights the potential of circFGFR1 as a therapeutic target, offering insights into PTC's molecular mechanisms, and paving the way for novel treatment strategies.

Use of Palpation Imaging in Diagnosis of Breast Diseases: A Way to Improve the Detection Rate.

BACKGROUND Breast diseases pose increasing threat to women health as peoples lifestyle changes. The aim of this study was to investigate the clinical application value of Palpation Imaging (PI) in the diagnosis of breast diseases. MATERIAL AND METHODS From October 2019 to February 2020, 184 patients with 225 breast lesions were examined by using PI, ultrasound, and mammography in the department of Breast Surgery, the First Affiliated Hospital of Anhui Medical University. All cases were confirmed pathologically by core-needle biopsy or excisional biopsy. The cut-off value of the PI tests was determined by receiver operating characteristic (ROC) curve. We compared the examination results of PI with ultrasound and mammography to analyze the diagnostic value of PI. RESULTS Pathological examination revealed that 186/225(82.67%) lesions were benign, while 39 were malignant. All 8 parameters of PI were significantly correlated with pathological findings (P<0.05). The best cut-off value for the PI score was 19.5 and the area under the curve (AUC) for the PI was 0.921 (95% CI: 0.874-0.968, P<0.001) with 89.7% sensitivity and 86.0% specificity. PI showed greater sensitivity (89.7%) and its specificity (86.0% vs. 86.4%, P=0.931) and accuracy (86.7% vs. 84.6%, P=0.604) were similar to those of mammography. The combination of 3 types of test is superior to a single examination. The sensitivity was 100% and the specificity was 98.8%. CONCLUSIONS PI has high clinical value in differentiation of benign and malignant breast lesions. Combination examination has the potential to improve the detection of breast cancer in screening and diagnostic capacities and can be used as a supplement to ultrasound and mammography.

CELF6 modulates triple-negative breast cancer progression by regulating the stability of FBP1 mRNA.

BACKGROUND: Triple-negative breast cancer (TNBC) remains a great challenge in clinical treatment due to a shortage of effective therapeutic targets and acquired chemoresistance. Here, we identified the role of an RNA-binding protein, CUG-BP Elav-like family member 6 (CELF6), in the TNBC development and paclitaxel (PTX) chemoresistance. METHODS: Stable CELF6-overexpressing cell lines were established in BT549 and MDA-MB-231 cells. Cell proliferation was determined using cell counting, two-dimensional colony formation, and MTT assay. Meanwhile, cell migration and cell invasion were detected by Transwell assay. Furthermore, the downstream target gene of CELF6 was identified and the direct interaction was further determined by luciferase reporter assay, immunoprecipitation, and RNA pull-down. Additionally, the PTX resistant cell line was established to determine the role of CELF6 in PTX resistance. RESULTS: CELF6 overexpression suppressed cell proliferation, cell migration, and cell invasion. Mechanistically, Fructose-Bisphosphatase 1 (FBP1) was identified as the target gene of CELF6 and stabilized by CELF6 via binding 3'UTR. CELF6 overexpression mediated inhibition in TNBC development was dependent on FBP1. Moreover, CELF6 overexpression increased the sensitivity to PTX treatment. CONCLUSION: CELF6 functions as a tumor suppressor by upregulating FBP 1 expression via stabilizing its mRNA, and thereby inhibits TNBC progression.

Correlation between FAS single nucleotide polymorphisms and breast carcinoma susceptibility in Asia.

BACKGROUND: FAS cell surface death receptor (FAS) gene has 2 common single nucleotide polymorphisms (SNPs) in its promoter, FAS-1377G > A (rs2234767) and FAS-670A > G (rs1800682). Several studies have investigated the role of these 2 polymorphisms in etiology of breast cancer in Asian population while the outcomes are inconsistent. To derive a more precise assessment of the association between breast cancer susceptibility with FAS gene promoter SNPs, a meta-analysis of published studies was performed. MATERIAL AND METHODS: We systematically searched PubMed, Embase, Web of Science, and the Chinese biomedical database (CBM) for papers published until November 1, 2018. Odds ratio (OR) with 95% confidential interval (95%CI) was conducted to evaluate the associations. Statistical analysis was conducted using Stata13.0 software. A total of 8 studies covering 2564 cases and 2633 controls were included. RESULTS: The integrated results suggest the following: For the FAS-1377G/A polymorphism, we only found significant associations for allele G vs allele A (OR = 1.100, 95%CI = 1.004-1.206, P = .040). After stratification by ethnicity, a significant association was observed only for the AA+GA vs GG genotype in East Asian populations (OR = 1.177, 95% CI = 1.010-1.371, P = .037). The association was not found in West Asian populations. For the FAS -670A/G polymorphism, no association with cancer risk was found in any comparison model. Sensitivity analysis suggests that the meta-analysis results obtained after excluding any single study were similar to the original ones, suggesting that the meta-analysis results were not significantly affected by any single study. CONCLUSION: These results indicated that FAS-1377G/A polymorphism may contribute to the increased breast cancer susceptibility and could be a promising target for cancer risk prediction. Further studies are needed to determine if the FAS gene confers a risk of breast cancer in other ethnic groups, such as Africans and Latin Americans.

Association of CAV1 polymorphisms with the risks of breast cancer: A systematic review and meta-analysis.

BACKGROUND: Caveolin-1 (CAV1) polymorphisms have been shown to correlated with breast cancer risk in previous studies. However, the role of CAV1 polymorphisms still remained indecisive, and dual functions of CAV1 was demonstrated in breast cancer development. Consequently, a meta-analysis to evaluate and summarize the association of the CAV1 polymorphisms with breast cancer susceptibility. MATERIAL AND METHODS: Extensive search was performed in PubMed, Web of Science, Google scholar, EMBASE.com, CNKI and Wanfang searching platform up to March 2019. The Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of each study. The Odds ratios (ORs) and the 95% confidence intervals (CIs) were analyzed to evaluate the strength of the associations in five genetic models. Inter-study heterogeneity was quantified using the I-squared (I2) test. In addition, the Egger's test and Begg's test were applied to evaluate the publication bias. RESULTS: 4 case-control studies with 2115 cases and 2138 controls were enrolled into this analysis. There was a significant association between rs3807987 polymorphism of CAV1 and breast cancer in allele comparison (A vs. G: OR = 1.288, 95％CI = 1.162-1.428, P < 0.001), heterozygote comparison (AG vs. GG: OR= 1.422, 95％CI=1.233-1.639, P < 0.001), and dominant comparison (AA+AG vs. GG: OR=1.395, 95％CI=1.228-1.586, P < 0.001). A significant association of rs3807987 polymorphism in allele comparison (A vs. G: OR=1.238, 95％CI=1.109-1.383, P < 0.001), heterozygote comparison (AG VS. GG: OR=1.466, 95％CI=1.267-1.697, P < 0.05), and dominant comparison (AA+AG vs. GG: OR=1.384, 95％CI=1.209-1.585, P < 0.001) was also founded amongst Chinese population. A significant association between rs7804372 polymorphism and breast cancer amongst Chinese population in recessive comparison (AA vs. AT + TT: OR = 0.730, 95％CI = 0.567-0.940, P = 0.015) was identified. No significant association between breast cancer risk and rs1997623 was found. CONCLUSION: CAV1 rs3807987 and rs7804372 polymorphisms are associated with the change of breast cancer risk. More well-designed and large studies in various populations are needed to further elaborate these associations.

TMED3 promotes cell proliferation and motility in breast cancer and is negatively modulated by miR-188-3p.

BACKGROUND: The role of TMED3 involved in cancers has been seldom described, let alone in breast cancer. To explore the clinicopathological significance of TMED3 expression and the biological roles involved in breast cancer cells, we undertook the study. METHODS: Immunohistochemistry was performed to observe the pattern of TMED3 expression in breast cancer tissues, totaling 224 cases; followed by detailed statistical analysis between TMED3 expression versus clinicopathological information available. To explore the role of TMED3 involved in the malignant behaviors of breast cancer cells, wound-healing and Transwell assays were conducted to evaluate the variation of migration and invasion of MCF-7 and MDA-MB-231 cells whose TMED3 has been stably silenced using lenti-viral based short hairpin RNA (shRNA) vectors. MTT, clonogenic assay and xenograft nude mice model were undertaken to observe the variation of proliferation both in vitro and in vivo. RESULTS: It was shown that elevated TMED3 markedly correlated with ER, PR, Her-2 status, and lymph nodes metastases in addition to significant association with poor overall prognosis. In vitro, TMED3 was shown to promote proliferation, migration and invasion of breast cancer cells. Moreover, miR-188-3p was identified as a novel negative regulator of TMED3 in breast cancer, which can slow down the proliferation, migration and invasion of MCF-7 cells. Results from in vivo xenograft nude mice models showed that lenti-viral based miR-188-3p re-expression can markedly impair the tumor growth. CONCLUSIONS: Our data define and bolster the oncogenic role of TMED3 in breast cancer.

NEK5 promotes breast cancer cell proliferation through up-regulation of Cyclin A2.

NEK5, a contraction of NIMA Related Kinase 5, has been shown to regulate the centrosome integrity of cells though; it has been little described in cancer. Herein, to explore the clinicopathological meaning of NEK5 expression in breast cancer, immunohistochemistry was performed to detect the expression of NEK5 on tissue blocks, totaling 203 cases. Quantitative real-time PCR (qRT-PCR) was used to evaluate NEK5 mRNA expression with 30 cases of fresh tissues. To observe the function of NEK5 in the growth of breast cancer cells, both MTT and xenografted nude mice were performed. And Transwell assay was employed to observe the variation of migration and invasion. It was shown that up-regulated NEK5 was significantly associated with tumor progression and poor overall prognosis; and that silencing of NEK5 can significantly suppress the proliferation both in vivo and in vitro, inhibiting migration, and invasion. To get insight into the underlying mechanism by which NEK5 operates in proliferation of breast cancer cells, we showed that NEK5 can up-regulate Cyclin A2 and down-regulate Cyclin D1, Cyclin D3, and Cyclin E1 expression. Additionally, Cyclin A2 was also identified as a novel interacting protein for NEK5. Taking together, we firstly defined the oncogenic role of NEK5 in breast cancer that was related to proliferation, supporting that NEK5 might be used a new therapeutic target in breast cancer.

Curcumin synergistically increases effects of ß-interferon and retinoic acid on breast cancer cells in vitro and in vivo by up-regulation of GRIM-19 through STAT3-dependent and STAT3-independent pathways.

OBJECTIVE: The study aimed to investigate the effects of combination treatment of curcumin and ß-interferon (IFN-ß)/retinoic acid (RA) on breast cancer cells, including cell viability, apoptosis and migration, and to determine the mechanisms related to GRIM-19 through STAT3-dependent and STAT3-independent pathways. METHODS: The following groups were used for the in vitro experiment: control siRNA, GRIM-19 siRNA, IFN-ß/RA and IFN-ß/RA + curcumin. Cell viability is by the MTT method, cell apoptosis by flow cytometry and cell migration by wound healing experiment; GRIM-19, STAT3, survivin, Bcl-2, GADD153 and COX-2 expression was measured by Western blot. In vivo experiment, MCF-7 cells were subcutaneously injected into nude mice. RESULTS: GRIM-19 siRNA promoted MCF-7 cell proliferation and migration; inhibited cell apoptosis; and promoted the expression of STAT3, survivin, Bcl-2 and MMP-9. IFN-ß/RA inhibited cell proliferation and migration; promoted cell apoptosis; up-regulated GRIM-19; and inhibited the expression of STAT3, survivin, Bcl-2 and MMP-9. Combination treatment of curcumin and IFN-ß/RA had a stronger effect than that of the IFN-ß/RA group. In addition, curcumin and IFN-ß/RA combination inhibited the expression of COX-2 and up-regulated GADD153. CONCLUSION: Curcumin synergistically increases the effects of IFN-ß/RA on breast cancer cells. The mechanism may be related to the up-regulation of GRIM-19 through STAT3-dependent and STAT3-independent pathways.

A Wearable Goggle Navigation System for Dual-Mode Optical and Ultrasound Localization of Suspicious Lesions: Validation Studies Using Tissue-Simulating Phantoms and an Ex Vivo Human Breast Tissue Model.

Surgical resection remains the primary curative treatment for many early-stage cancers, including breast cancer. The development of intraoperative guidance systems for identifying all sites of disease and improving the likelihood of complete surgical resection is an area of active ongoing research, as this can lead to a decrease in the need of subsequent additional surgical procedures. We develop a wearable goggle navigation system for dual-mode optical and ultrasound imaging of suspicious lesions. The system consists of a light source module, a monochromatic CCD camera, an ultrasound system, a Google Glass, and a host computer. It is tested in tissue-simulating phantoms and an ex vivo human breast tissue model. Our experiments demonstrate that the surgical navigation system provides useful guidance for localization and core needle biopsy of simulated tumor within the tissue-simulating phantom, as well as a core needle biopsy and subsequent excision of Indocyanine Green (ICG)-fluorescing sentinel lymph nodes. Our experiments support the contention that this wearable goggle navigation system can be potentially very useful and fully integrated by the surgeon for optimizing many aspects of oncologic surgery. Further engineering optimization and additional in vivo clinical validation work is necessary before such a surgical navigation system can be fully realized in the everyday clinical setting.

Smac mimetic­induced caspase­independent necroptosis requires RIP1 in breast cancer.

There is an urgent requirement for the development of novel targeted therapies to treat breast cancer, which is the most comment type of malignancy among women. The evasion of apoptosis is a hallmark of cancer, and is often due to the upregulation of inhibitor of apoptosis proteins (IAPs) in tumor cells. Second mitochondrial­derived activator of caspase/direct IAP­binding protein with low PI is a natural IAP antagonist, which is found in the mitochondrion; this protein has a motif, which binds to a surface groove on the baculovirus IAP repeat domains of the IAPs. In the present study, the effects of the LCL161 Smac mimetic, a small molecule IAP antagonist, on breast cell lines was examined. The results from MTT and colony formation assays demonstrated that LCL161 markedly inhibited the proliferation and induced the apoptosis of MDA­MB­231 and MCF­7 cell lines. As determined by western blotting, cIAP1 was degraded in the breast cancer cells, which occurred in an LCL161­dependent manner. Upon caspase activation, LCL161 treatment induced necroptosis, another form of programmed cell death. The downregulation of receptor­interacting protein kinase­1 via small interfering RNA protected the cells from LCL161­induced necroptosis. Taken together, the results of the present study showed that LCL161 can induce multiple forms of programmed cell death in breast cancer cells, and may thus offer promise as an anticancer agent in diverse genotypic backgrounds.

Negative regulation of CDC42 expression and cell cycle progression by miR-29a in breast cancer.

OBJECTIVE: The inhibitory role of microRNA-29a (miR-29a) has been assessed in breast cancer cells. Herein, we analyze the underlying mechanisms of its role in cell cycle progression in breast cancer cells. METHODS: We applied real-time polymerase chain reaction (PCR) to detect the expression of miR-29 in breast cancer cell lines. Then one of the cell lines, MDA-MB-453, was transfected with mimics of miR-29a. The cell cycle was analyzed by fluorescence-activated cell sorting after staining the cells with propidium iodide. Real-time PCR, luciferase assay and western blot were used together to verify the regulation of the predicted target, cell division cycle 42 (CDC42) by miR-29a. RESULTS: MiR-29s were decreased in our selected mammary cell lines, among which miR-29a was the dominant isoform. Overexpression of miR-29a caused cell cycle arrest at the G0/G1 phase. We further found that miR-29a could target the expression of CDC42, which is a small GTPase associated with cell cycle progression. CONCLUSION: We suggest that miR-29a exerts its tumor suppressor role in breast cancer cells partially by arresting the cell cycle through negative regulation of CDC42.

Notch-1 promotes breast cancer cells proliferation by regulating LncRNA GAS5.

BACKGROUND: Notch signaling is indicated as novel therapeutic targets to prevent recurrence of breast cancer. LncRNAs were identified as downstream target of Notch pathway. However, the exact mechanisms involved in Notch signaling, lncRNAs and breast cancer remain to be explained. OBJECTIVE: This original research aimed to determine the prognostic implications of Notch-1 for breast cancer, and explain mechanisms involved in regulation of lnRNA GAS5 by Notch-1, and identify the function of this mechanism on breast cancer. METHOD: Thirty breast cancer patients were included from The First Affiliated Hospital of Anhui Medical University (China) since January 2006 in this study. The mRNA level by RT-PCR and protein level of Notch-1 by western blot in tumor tissues and adjacent normal tissues were evaluated and 5-year survival analysis was applied to examine the significance of Notch-1. The levels of ten reported lncRNAs were determined by RT-PCR, and subsequently linear analysis was applied to analyze the relationship between these four unique lncRNAs and protein level of Notch-1, which identified the most relevant lncRNA GAS5 with Notch-1 in breast cancer. Subsequently, Notch1-siRNA was applied to influence the expression of Notch-1 in T47D, then the level of RSA5 was measured by RT-PCR, and CCK-8 assay was applied to measure the proliferation of T47D cells. RESULTS: High level of Notch-1 provided a poor prognosis in breast cancer. Interference of Notch-1 significantly suppressed proliferation of T47D cell (P < 0.05), and significantly increased the level of GAS5. CONCLUSION: Notch-1 promotes breast cancer cells proliferation by regulating LncRNA GAS5.

Herceptin as a single agent in the treatment of patients with metastatic breast cancer.

OBJECTIVE: The aim of this retrospectively study was to assess the clinical efficacy and toxicity of Herceptin as a single agent in the treatment of patients with metastatic breast cancer (MBC). METHODS: We retrospectively included and analyzed 31 metastasis breast cancer patients in our patient database. All of the included 31 patients were pathology confirmed of breast carcinoma with remote metastases and treated with Herceptin as a single agent. The clinical efficacy and drug-related toxicity were analyzed. RESULTS: No complete response patients were observed for 31 cases. And 8 (26%) reached partial response 16 (52%) with stable disease. The objective response rate of the 31 patients was 23%. We further divided the 31 cases into three subgroups according to the treatment modality. The objective response rate was 36%, 14%, and 17% for the first-line, second-line, and third-line treatment modality, respectively. The objective response rate was not statistical different among the three subgroups (P > 0.05). The main drug-related adverse event were asthenia, chills, diarrhea, nausea, hypotension and dizziness with their incidence of 68%, 26%, 13%, 10%, 10%, and 6%, respectively, for each patients. CONCLUSION: Herceptin as a single agent was effective and safe in the treatment of patients with MBC.

The combination of inferior pedicle method and dermal suspension sling technique: one new efficient method for breast reduction.

OBJECTIVE: To explore a method of breast reduction which ensures well nipple and areola lactation function, adequate blood supply and good medial fullness and projection. At the same time, this study could evaluate the advantages of the combination of inferior pedicle method and dermal suspension sling technique for breast reduction. METHODS: From 2011.11 to 2013.8, 13 women have undergone breast reduction using utilizing inferior pedicle combined with the dermal suspension sling technique. The inferior pedicle was designed with medial and lateral triangular flaps in the areas where normally be excised. These triangular flaps were deepithelialized and defatted. The flaps were attached to the chest wall above the inferior pedicle to create a dermal "cage". RESULTS: After operation, Sensation of nipple and areola complex, breast projection and shape were sustained during follow-up, of which the median interval was 12 months. No patient had poor projection and bottoming out. CONCLUSION: Dermal suspension and horizontal dermal placation provides a structural foundation to the inferior pedicle. It is an effective method of treatment for breast reduction, in that the sensation and lactation function of nipple and areola complex get further guaranteed, have nice breast projection and shape, and can be applied to all cases of breast reduction.

Dosimetric absorption of intensity-modulated radiotherapy compared with conventional radiotherapy in breast-conserving surgery.

The aim of this study was to investigate the dosimetric benefits between intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (CR) among patients receiving breast-conserving surgery. A dosimetric comparison of IMRT and CR was evaluated in 20 patients with early-stage breast cancer using a three-dimensional treatment planning system. The prescribed mammary gland dose was completed in 25 fractions with a total dose of 5,000 cGy. Homogeneity of the planning target volume (PTV), irradiation dose and volume of organs at risk (OARs) were evaluated through a dose-volume histogram. For the homogeneity of PTV, the average volume receiving 95% of the prescribed dose in the IMRT plan was similar to that in the CR plan (97 vs. 96%, respectively). With regard to normal tissue sparing in OARs, the ipsilateral lung V20 in the IMRT and CR plans was 27.8 and 20.8%, respectively. The mean dose and V30 of the heart for five patients were 598.4 versus 348.3 cGy and 10.06 versus 5.3%, respectively. The mean dose sparing the heart or lung was markedly reduced in the IMRT plan compared with the CR plan. The results of the current study demonstrated that whole breast IMRT improves PTV dose distribution and improves normal tissue sparing in OARs.

[Nipple reduction by using a modified Z-shaped incision technique].

OBJECTIVE: To explore an ideal surgical method for nipple hypertrophy correction. METHODS: From July 2008 to June 2011, 44 nipple reductions were performed for 22 women (44 sides) by using the modified Z-shaped incision technique. The incision consists of two circles, one quadrangle and one triangle located on the top, body and base of the nipple. The nipple's height was decreased and the nipple diameter and base area were reduced. Bilateral nipples were designed symmetrically. RESULTS: 22 cases(44 sides) were treated with primary healing. The mean diameter of the nipple was reduced to (9.8 +/- 1.6) mm from (17.6 +/- 3.4) mm, the average height from (18.8 +/- 3.6) mm to (8.2 +/- 1.4) mm, with the patient supine. All the patients were followed up for 14 months to 4 years with satisfactory results. No nipple necrosis, infection and numb happened. 20 patients completed the self-designed survey scale 1 year after operation, of which 4 cases achieved normal lactation, and the remaining patients didn't have childbirth and breastfeeding yet. CONCLUSIONS: The modified Z-shaped incision technique could reduce the height, diameter, and most importantly, reduce the basal shape of all types of hypertrophic nipple to create a desired new cylindrical nipple without affection of nipple sensation and function.

A common variant in the SIAH2 locus is associated with estrogen receptor-positive breast cancer in the Chinese Han population.

BACKGROUND: Genome-wide association studies (GWAS) have identified many loci associated with breast cancer risk. These studies have primarily been conducted in populations of European descent. OBJECTIVE: To determine whether previously reported susceptibility loci in other ethnic groups are also risk factors for breast cancer in a Chinese population. METHOD: We genotyped 21 previously reported single nucleotide polymorphisms (SNPs) within a female Chinese cohort of 1203 breast cancer cases and 2525 healthy controls using the Sequenom iPlex platform. Fourteen SNPs passed the quality control test. These SNPs were subjected to statistical analysis for the entire cohort and were further analyzed for estrogen receptor (ER) status. The associations of the SNPs with disease susceptibility were assessed using logistic regression, adjusting for age. The Bonferroni correction was used to conservatively account for multiple testing, and the threshold for statistical significance was P<3.57×10(-3) (0.05/14). RESULT: Although none of the SNPs showed an overall association with breast cancer, an analysis of the ER status of the breast cancer patients revealed that the SIAH2 locus (rs6788895; P = 5.73×10(-4), odds ratio [OR] = 0.81) is associated with ER-positive breast cancer. CONCLUSION: A common variant in the SIAH2 locus is associated with ER-positive breast cancer in the Chinese Han population. The replication of published GWAS results in other ethnic groups provides important information regarding the genetic etiology of breast cancer.

Single nucleotide polymorphism 6q25.1 rs2046210 and increased risk of breast cancer.

The onset and development of breast cancer (BC) are influenced by many factors, including the single nucleotide polymorphism (SNP) rs2046210 at 6q25.1. However, studies of the potential association between rs2046210 at 6q25.1 and risk of BC have given inconsistent results. We performed a meta-analysis to address this controversy. PubMed, EMBASE, and Web of Science were systematically searched to identify relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association between this SNP and risk of BC. A total of 14 studies are included in the meta-analysis, involving 123,085 cases and 120,761 controls. The A-allele, AA/GA, and AA genotypes were significantly associated with increased risk of BC (A-allele vs. G-allele: OR = 1.20, 95%CI = 1.15-1.25, P for heterogeneity < 0.0001; AA/GA vs. GG: OR = 1.22, 95%CI = 1.16-1.28, P for heterogeneity < 0.0001; AA vs. GA/GG: OR = 1.18, 95%CI = 1.13-1.24, P for heterogeneity = 0.064). In further stratified analysis by ethnicity, the elevated risks were found in Europeans and Asians, while there was no significant association detected in African population. In the subgroup analysis based on sample size and source of control, significant results were observed in all the subgroups. There was evidence of heterogeneity (P < 0.10), which largely disappeared after stratification by ethnicity. In summary, this meta-analysis suggests the participation of rs2046210 at 6q25.1 in the susceptibility for BC, especially in Europeans and Asians.

Three novel antimicrobial peptides from the skin of Rana shuchinae.

Intensive studies have demonstrated that there are many antimicrobial peptides in amphibian skins. Three novel antimicrobial peptides were identified from the skin of the frog, Rana shuchinae. They are named shuchins 3-5. Their sequences were determined as KAYSMPRCKGGFRAVMCWL-NH2, KAYSTPRCKGLFRALMCWL-NH2, and KAYSMPRCKYLFRAVLCWL-NH2 by Edman degradation and mass spectrometry analysis, respectively. They are composed of 19 amino acids (aa) with unique sequences. BLAST search indicated that they showed no similarity to any known peptides or proteins. They are a novel family of antimicrobial peptide. These peptides showed antimicrobial activities against all of tested microorganisms including Gram-positive bacteria, Gram-negative bacteria and fungi. The cDNAs encoding precursors of these peptides were cloned from the skin cDNA library of R. shuchinae. The precursors are composed of 64 amino acid residues including predicted signal peptides, acidic spacer peptides, and mature antimicrobial peptides. The current work identified a novel antimicrobial peptide family.