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To explore the learning curve of high intensity focus ultrasound (HIFU) treatment for breast fibroadenoma.A database of 110 patients with 255 breast fibroadenomas who underwent HIFU treatment at two different clinical centers (Center 1 and 2) were retrospectively analyzed. The learning curves of HIFU treatment for breast fibroadenoma were drawn by CUSUM analysis in two centers, respectively. According to the inflection point of the learning curves, the treatment was divided into two groups: initial phase and consolidation phase. HIFU treatment parameters were compared between two groups. The effectiveness and safety results were also evaluated.The inflection points of the learning curves were the 60HIFU treatment for breast fibroadenoma was effective and safe. The learning curve of HIFU treatment for breast fibroadenoma can be completed after treating 60-65 tumors without increasing the safety risk.

Circulating tumor cells (CTCs) have been shown to be associated with the response to neoadjuvant chemotherapy (NCT) and the prognosis of locally advanced breast cancer (LABC) patients. Our study aimed to investigate whether the change of CTC status during NCT could serve as a supplement to the Response Evaluation Criteria in Solid Tumors (RECIST) in the treatment and evaluation of LABC patients.6 ml of blood samples were collected before NCT, after the first cycle of NCT and after the completion of NCT, respectively. According to the change of CTC number during NCT, the patients were divided into "CTC low-response (low-R)" group and "CTC high-response (high-R)" group. Survival data of each group of patients were obtained through long-term follow-up.A total of 35 patients diagnosed with LABC were enrolled. The median follow-up for distant metastasis was 27 months (range 7-36 months). There was no significant difference in distant metastasis-free survival (DMFS) between PR/CR group and PD/SD group (P = 0.0914), while CTC low-R group had a worse DMFS than CTC high-R group (P = 0.0199). In PR/CR subgroup, patients with CTC low-R showed a lower DMFS compared with those with CTC high-R (P = 0.0159). However, in PD/SD subgroup, there was no significant difference in DMFS between CTC low-R and CTC high-R group (P = 0.7521). In terms of assessing response to NCT, CTC change or RECIST classification alone had an AUC of 0.533 (95% CI 0.277-0.790) and 0.700 (95% CI 0.611-0.789), respectively. When combining the two, the AUC slightly increased to 0.713 (95% CI 0.532-0.895).The change of CTC number during NCT has a potential to serve as a supplement to RECIST in the assessment of NCT efficacy and the prognosis of LABC patients.

Asthma is the most common chronic respiratory disease and has been declared a global public health problem by the World Health Organization. Due to the high heterogeneity and complexity, asthma can be classified into different 'phenotypes' and it is still difficult to assess the phenotypes and stages of asthma by traditional methods. In recent years, mass spectrometry-based proteomics studies have made significant progress in sensitivity and accuracy of protein identification and quantitation, and are able to obtain differences in protein expression across samples, which provides new insights into the mechanisms and classification of asthma.In this article, we summarize research strategies in quantitative proteomics, including labeled, label-free and targeted quantification, and highlight the advantages and disadvantages of each. In addition, new applications of quantitative proteomics and the current status of research in asthma have also been discussed. In this study, online resources such as PubMed and Google Scholar were used for literature retrieval.The application of quantitative proteomics in asthma has an important role in identifying asthma subphenotypes, revealing potential pathogenesis and therapeutic targets. But the proteomic studies on asthma are not sufficient, as most of them are in the phase of biomarker discovery.

Background. To construct and validate a radiomic-based model for estimating axillary lymph node (ALN) metastasis in patients with breast cancer by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods. In this retrospective study, a radiomic-based model was established in a training cohort of 236 patients with breast cancer. Radiomic features were extracted from breast DCE-MRI scans. A method named the least absolute shrinkage and selection operator (LASSO) was applied to select radiomic features based on highly reproducible features. A radiomic signature was built by a support vector machine (SVM). Multivariate logistic regression analysis was adopted to establish a clinical characteristic-based model. The performance of models was analysed through discrimination ability and clinical benefits. Results. The radiomic signature comprised 6 features related to ALN metastasis and showed significant differences between the patients with ALN metastasis and without ALN metastasis ( P < 0.001 ). The area under the curve (AUC) of the radiomic model was 0.990 and 0.858, respectively, in the training and validation sets. The clinical feature-based model, including MRI-reported status and palpability, performed slightly worse, with an AUC of 0.784 in the training cohort and 0.789 in the validation cohort. The radiomic signature was confirmed to provide more clinical benefits by decision curve analysis. Conclusions. The radiomic-based model developed in this study can successfully diagnose the status of lymph nodes in patients with breast cancer, which may reduce unnecessary invasive clinical operations.

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is characterized by asthma-like attacks in its early stage, which is easily misdiagnosed as severe asthma. Therefore, new biomarkers for the early diagnosis of EGPA are needed, especially for differentiating the diagnosis of asthma.ObjectivesTo identify serum biomarkers that can be used for early diagnosis of EGPA and to distinguish EGPA from severe asthma.MethodData-independent acquisition (DIA) analysis was performed to identify 45 healthy controls (HC), severe asthma (S-A), and EGPA patients in a cohort to screen biomarkers for early diagnosis of EGPA and to differentiate asthma diagnosis. Subsequently, parallel reaction monitoring (PRM) analysis was applied to a validation cohort of 71 HC, S-A, and EGPA patients.ResultFour candidate biomarkers were identified from DIA and PRM analysis—i.e., serum amyloid A1 (SAA1), fibrinogen-α (FGA), and serum amyloid P component (SAP)—and were upregulated in the EGPA group, while cholesteryl ester transfer protein (CETP) was downregulated in the EGPA group compared with the S-A group. Receiver operating characteristics analysis shows that, as biomarkers for early diagnosis of EGPA, the combination of SAA1, FGA, and SAP has an area under the curve (AUC) of 0.947, a sensitivity of 82.35%, and a specificity of 100%. The combination of SAA1, FGA, SAP, and CETP as biomarkers for differential diagnosis of asthma had an AUC of 0.921, a sensitivity of 78.13%, and a specificity of 100%, which were all larger than single markers. Moreover, SAA1, FGA, and SAP were positively and CETP was negatively correlated with eosinophil count.ConclusionDIA-PRM combined analysis screened and validated four previously unexplored but potentially useful biomarkers for early diagnosis of EGPA and differential diagnosis of asthma.

To investigate the factors influencing the sonication dosage and efficiency of ultrasound-guided high intensity focused ultrasound (USgHIFU) for breast fibroadenomas.Forty-nine patients with 78 breast fibroadenomas who underwent USgHIFU were retrospectively analyzed. The energy efficiency factor (EEF) was set as dependent variable, and the factors possibly influencing the sonication dosage, including age, body mass index (BMI), fibroadenoma size, distance from the shallow margin of the fibroadenoma to skin, distance from the deep margin of the fibroadenoma to pectoralis major, types of near field acoustic pathway, and Adler blood flow classification of ultrasound, were set as independent variables. The correlation between EEF and these independent variables were analyzed, and an optimal scaling regression model was established.Fibroadenoma size, distance from the shallow margin of the fibroadenoma to skin and type of near field acoustic pathway had significant correlation with EEF (Fibroadenoma size, distance from the shallow margin of the fibroadenoma to skin and type of near field acoustic pathway could be used as predictors to evaluate the dosage delivery of USgHIFU treatment for breast fibroadenomas.

The incidence of breast cancer (BC) is the highest among women. Identification of miRNAs as biomarkers may help to improve the diagnosis of BC. The purpose of this study was to assess the expression levels of miR-1976 in plasma samples and the biological functions in the progression of BC. The expression levels of miR-1976 in plasma samples and tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The associations between the expression levels and clinicopathological features were studied. Cell supernatants were used to simulate circulation. The biological functions of miR-1976 were assessed in vitro and in vivo. The expression levels of miR-1976 in plasma samples were found significantly lower in patients with BC than those in healthy controls, and were associated with Ki-67. The expression levels in BC tissues were lower than those in adjacent normal tissues, and were correlated with the number of lymph nodes and Ki-67. The expression levels in BC cell supernatants and cell lines were lower than that in normal human breast epithelial cell line HBL-100. miR-1976 knockdown promoted proliferation in vitro and in vivo. miR-1976 may serve as a promising non-invasive biomarker for the diagnosis of BC in the future.

To determine the characteristics of ultrasound (US) imaging of completely ablated cases and the effects of duration and clinical experience on accurate microwave ablation (MWA) for the treatment of benign breast tumours.With written informed consent and approval of the institutional ethics committee, patients with symptomatic or palpable benign breast tumours (longest diameter, 7-32 mm), to whom MWA (2450 MHz) was performed, were enrolled in this prospective nonrandomised study. US and contrast-enhanced US (CEUS) images were applied for follow-up and analysed.Forty-seven consecutive patients with 52 completely ablated tumours were enrolled. Of these 52 tumour ablations in US, 16 ablations were defined as concentric type, and 36 were defined as nonconcentric type. Of these 52 ablations, 7 cases were defined as nonaccurate ablation with the largest margin ≥10 mm in US. The nonaccurate ablation rate in the training group (the first consecutive 30 cases, 7/30) was significant higher than that (the last 22 cases, 0/22) in the practiced group (p = 0.016). Of 38 completely ablated cases (9 mm the longest diameter20 mm), the average largest margin in70 s group was significant larger than that in70 s group (p = 0.019).Experience was important for accurate MWA in the treatment of benign breast tumour, and at least 30 cases training was recommended. Nevertheless, clinical trials are still required to validate our findings in the future.

BACKGROUND Epithelial to mesenchymal transition (EMT) contributes to metastases in various types of tumors, and is also the key step in the breast cancer metastatic cascade. In our previous study, a mouse model containing human-derived normal breast tissue was established and allowed EMT/MET process of human breast cancer cells to be mimicked in a humanized mammary microenvironment. MATERIAL AND METHODS Two-dimensional electrophoresis (2-DE) and mass spectrometry were used to detect different proteins between parental MDA-MB-231 and its variant sub-line obtained from tumors grown in transplanted normal human breast tissue (MDA-MB-231br). We knocked down the ezrin in 2 cell lines (MDA-MB-231 and SUM1315). The migration and invasion ability was assessed. EMT markers were examined by real-time reverse transcription PCR analysis and Western blot analysis. The relationship of ezrin with cortactin was tested by tissue microarray and co-immunoprecipitation. RESULTS Proteomic analysis revealed 81 differentially expressed proteins between parental MDA-MB-231 and MDA-MB-231br. Among these proteins, the expression of ezrin and cortactin and the phosphorylation of ezrin were significantly correlated, accompanied with a group of classic EMT makers. Knockdown of ezrin reversed the expression of EMT markers and downregulated cortactin and EMT transcription factors. Ezrin silencing inhibited tumor cell migration and invasion. Breast cancer tissue microarray and immunohistochemistry showed a significant positive association between ezrin and cortactin. CONCLUSIONS These findings indicate that ezrin is correlated with cortactin in facilitating EMT in breast cancer. The interaction between ezrin and cortactin is a novel mechanism contributing to the EMT process in cancer metastases.

Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases such as steatosis, cirrhosis, and hepatocellular carcinoma. HCV particles have been found to associate with apolipoproteins, and apolipoproteins not only participate in the HCV life cycle, but also help HCV escape recognition by the host immune system, which pose challenges for the development of both HCV treatments and vaccines. However, no study has reported on the comprehensive identification of apolipoprotein associations with HCV particles. In the present study, we performed proteome analysis by affinity purification coupled with mass spectrometry (AP-MS) to comprehensively identify the apolipoprotein associations with HCV particles, and ApoM was first identified by AP-MS besides the previously reported ApoE, ApoB, ApoA-I and ApoC-I. Additionally, three assays further confirmed that ApoM was a novel virus particle associated protein. We also showed that ApoM was required for HCV production, especially for the assembly/release step of HCV life cycle. Furthermore, ApoM interacted with the HCV E2 protein. Finally, HCV infection reduced ApoM expression both in vitro and in vivo. Collectively, our study demonstrates that ApoM, identified as a novel HCV particle associated protein, contributes to HCV assembly/release and interacts with HCV E2 protein. It provides new insights on how HCV and the host apolipoproteins are reciprocally influenced and lays a basis for research in developing innovative antiviral strategies.

Aims: To determine the factors influencing ultrasound breast tumor size assessment accuracy.Material and methods: Five factors (tumor type, molecular subtype, histological size, histological grade, and breast density) were used to assess the measurement accuracy of breast ultrasound in tumor size. Size underestimation was defined as ultrasound index lesion diameter < histological size by at least 5 mm.Results: Breast ultrasound underestimated tumor size significantly, especially in cases with intraductal components (p=0.002). There was a tendency for higher size underestimation in breast cancer tumors with high–histological grade (p=0.03), human epidermal growth factor receptor type 2 (HER2)-overexpressing breast cancer tumors (p=0.02) and hormone receptor (HR)−/HER2+ breast cancer tumors (p=0.008). Furthermore, core biopsy revealedhigher probability of size underestimation with intraductal components (p=0.002). Size underestimation was more frequent with larger histological size (p

Background: Women with triple negative breast cancers (TNBCs) have a poor prognosis due to lack of suitable targeted therapies. Changes in the protein glycosylation are increasingly being recognized as an important modification associated with cancer etiology. Methods: In an attempt to identify TNBC biomarkers with greater diagnostic and prognostic capabilities, hydrazide- based chemistry method combined with LC-MS/MS were used to purify and identify N-linked glycopeptides or glycoproteins of tissues from TNBC patients. Results: A total of 550 unique N-linked glycoproteins were identified, among these proteins, 72 unique N-linked glycoproteins were significantly regulated in tumor tissues, of which 56 proteins were upregulated and 16 proteins were downregulated. To assess the validity of the results, three selected proteins including Vascular endothelial growth factor receptor 1, Insulin receptor, Tissue factor pathway inhibitor were selected for western blot analysis, and these proteins were found as potential biomarkers of TNBC. The top three pathways of differentially expressed glycoproteins participated in were caveolar-mediated endocytosis signaling, agrin interactions at neuromuscular junction and LXR/RXR activation. Conclusion: This work provides potential glycoprotein markers to function as a novel tissue-based biomarker for TNBC.

Background Aldehyde dehydrogenase 1 (ALDH1) is an important marker of tumor-initiating cells. We aimed to investigate ALDH1 expression in benign breast disease and human breast cancer of different histologic stages. Methods Immunohistochemical staining of ALDH1 was applied to 21 cases with benign breast diseases, 47 ductal carcinoma in situ (DCIS) cases, 62 cases diagnosed with invasive cancer with extensive intraductal component (EIC), and 58 cases diagnosed with invasive cancer without EIC. Results ALDH1 was expressed in tumor cells in 61.0 % of 164 breast cancer cases, which was higher than that in benign breast disease (3/21) (P 0.05). However, ALDH1 positive invasive breast cancers were significantly more likely to be with large tumor size (P = 0.001), high grade (P

Background The objective of this study is to investigate the association among the polymorphisms of XRCC1 gene, smoking, drinking, family history of tumors, and the risk of colorectal cancer (CRC) in the population of Han nationality in Jiangsu Province, China. Methods A case–control study of 320 patients with CRC and 350 cancer-free subjects as a control group was conducted. The three polymorphic sites, codons 194, 280, and 399, of XRCC1 genes were analyzed by PCR-RFLP. Results We find that heavy smoking (>500 cigarettes per year) significantly increased the susceptibility of CRC (OR = 1.89, 95 % confidence interval (CI) 1.27–2.84) after stratification by total smoking amount. There was also significant difference between cases and controls when family history of tumors (OR = 2.96, 95 % CI 1.76–4.99) was considered. Comparing with individuals carrying XRCC1 399Arg/Arg genotype, the subjects with 399Arg/Gln (OR = 1.46, 95 % CI 1.06–2.01) or 399Gln/Gln genotype (OR = 1.93, 95 % CI 1.05–3.54) had a significantly increased risk for CRC. Taking smoking and drinking habits into consideration, we found that subjects with heavy smoking history and XRCC1 194Arg allele had the significantly increased risk for CRC (OR = 2.91, 95 % CI 1.35–6.24). Individuals, who carry 399Gln allele and have a heavy smoking (OR = 2.72, 95 % CI 1.52–4.89) or drinking habit (OR = 1.98, 95 % CI 1.06–3.67), also have higher risk. In smoking population, 194Arg (P = 0.491) and 399Gln (P = 0.912) had not significantly increased risk for CRC, so did 399Gln (P = 0.812) in smoking population. Conclusions Individuals carrying XRCC1 399Gln allele with a smoking or drinking habit were in increased risk, and heavy-smoking subjects with 194Arg allele also have higher risk for CRC in the Han nationality population of Jiangsu Province, which also showed a positive correlation with exposure dose of tobacco. But XRCC1 399Gln allele or 194Arg allele were not independent risk factors for CRC in smoking or drinking population.

Purpose To prospectively assess MR imaging evaluation of the ablation zone and pathological changes after microwave ablation (MWA) in breast cancer. Materials and methods Twelve enrolled patients, diagnosed with non-operable locally advanced breast cancer (LABC), were treated by MWA and then neoadjuvant chemotherapy, followed by surgery. MR imaging was applied to evaluate the effect of MWA. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were applied to analyze the ablated area. Results All MWA procedures were performed successfully under local anesthesia. For a mean duration of 2.15 min, the mean largest, middle and smallest diameters in the ablated zone 24-h post-ablation in MR imaging were 2.98 cm ± 0.53, 2.51 cm ± 0.41 and 2.23 cm ± 0.41, respectively. The general shape of the ablation zone was close to a sphere. The ablated area became gradually smaller in MR imaging. No adverse effects related to MWA were noted in all 12 patients during and after MWA. HE staining could confirm the effect about 3 months after MWA, which was confirmed by TEM. Conclusions 2 min MWA can cause an ablation zone with three diameters larger than 2 cm in breast cancer, which may be suitable for the local treatment of breast cancer up to 2 cm in largest diameter. However, the long-term effect of MWA in the treatment of small breast cancer should be determined in the future.

Background Few studies have systematically reported the relationship between the risk of breast cancer and family history of other cancers. This study was designed to systematically determine the relationship between breast cancer risk and family history of other cancers in first-degree relatives. Methods Between January 2006 and June 2011, 823 women diagnosed with breast cancer were included, and age-matched women diagnosed with benign breast disease were selected as controls. Family history of other cancers in first-degree relatives was recorded by trained reviewers. Multivariate logistic regression was applied to analyze the relationships. Results A family history of esophagus cancer (OR: 2.70, 95% CI: 1.11 – 6.57), lung cancer (OR: 2.49 95% CI: 1.10 – 5.65), digestive system cancer (OR: 1.79, 95% CI: 1.14 – 2.79) and any cancer (OR: 2.13, 95% CI: 1.49 – 3.04) in first-degree relatives was directly associated with increased breast cancer risk. In subgroup analysis, the risk of hormone receptor positive breast cancer was increased in subjects with a family history of lung cancer (OR: 3.37, 95% CI: 1.45 – 7.82), while the risk of hormone receptor negative breast cancer was increased in subjects with a family history of esophagus cancer (OR: 6.19, 95% CI: 2.30 – 16.71), uterus cancer (OR: 6.92, 95% CI: 1.12 – 42.89), digestive tract cancer (OR: 2.05, 95% CI: 1.03 – 4.10) and gynecology cancer (OR: 6.79, 95% CI: 1.46 – 31.65). Additionally, a significant increase in breast cancer was observed with a family history of digestive system cancer for subjects 50 y and younger (OR: 1.88, 95% CI: 1.03 – 3.43), not for subjects 50 y older (OR: 1.67, 95% CI: 0.86 – 3.25). Conclusions Breast cancer aggregates in families with several types of cancer especially for digestive system cancer. The influence of a family history of other cancers seems more likely to be limited to hormone receptor negative breast cancer.

Background The association between family history and risk of triple negative breast cancer and ductal carcinoma in situ (DCIS) has not been well investigated, especially in Asian populations. We investigated the association between family history and risk of DCIS or triple negative breast cancer in a Han Chinese population. Methods A case–control study, comprising 926 breast cancer patients and 1,187 benign breast disease controls, was conducted in our hospital. Multivariate logistic regression was used to assess the relationships between family history and risk of DCIS or triple negative breast cancer. Results Subjects with a family history of breast cancer had higher breast cancer risk than those without a family history (odds ratio (OR) = 2.11, 95% confidence interval (CI) = 1.26 to 3.52). Family history was not significantly associated with an increased risk of DCIS (OR = 1.27, 95% CI = 0.36 to 4.46), while family history was significantly associated with an increased risk of invasive breast cancer (OR = 2.22, 95% CI = 1.32 to 3.75), irrespective of triple negative breast cancer (OR = 3.35, 95% CI = 1.43 to 7.88) or non-triple negative breast cancer (OR = 2.14, 95% CI = 1.21 to 3.80). Conclusion Our results indicate that having a family history of breast cancer is associated with an increased risk of triple negative breast cancer with a magnitude of association similar to that for non-triple negative breast cancer. Furthermore, family history is not significantly associated with an increased risk of DCIS. Future cohort studies with larger sample sizes are still needed to explore these relationships.

BACKGROUND: Previous studies provide an ambiguous picture of creatine kinase (CK) expression and activities in malignancy. The aim of this study was to investigate the role of serum CK level in breast cancer patients. PATIENTS AND METHODS: 823 female patients diagnosed with breast cancer were consecutively recruited as cases, and 823 age-match patients with benign breast disease were selected as controls. Serum CK was analyzed by commercially available standardized methods. RESULTS: Serum CK level was significantly associated with breast cancer (P = 0.005) and subtypes of breast cancer, including breast cancer with diameter>2 cm (P = 0.031) and stage IIIbreast cancer (P = 0.025). The mean serum CK level in patients with>2 cm tumor was significantly lower than that in≤2 cm (P = 0.0475), and the mean serum CK level of stage III breast cancer patients was significantly lower than that of stage I and II breast cancer patients (P = 0.0246). Furthermore, a significant difference (P = 0.004) was observed between serum CK level and ERBB2+breast cancer not other molecular subtypes. CONCLUSIONS: Serum CK levels in cases was significantly lower compared with controls. Notably, our results indicated for the first time that there was a negative correlation between serum CK levels and breast cancer stage. Serum CK level, which may reflect the status of host immunity, may be an important factor in determining breast cancer development and progression.