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Purpose: Breast cancer is a highly heterogeneous malignancy, seriously threatening female health worldwide and inducing higher mortalities. Few have the studies evaluated Fms-like TyrosineKinase-3 (FLT3) in prognostic risk, immunotherapy or any other treatment of breast cancer. Our study focused on investigating the function of FLT3 in breast cancer. Patients and methods: Based on transcriptome and methylation data mined from The Cancer Gene Atlas (TCGA), we explored the clinical features of FLT3 expression in 1079 breast cancer samples. RT-qPCR in cell lines and tissue samples was used to verify the expression difference of FLT3. Kaplan-Meier survival analysis and cox regression models were employed for screening of FLT3 with potential prognostic capacity. Subsequently, functional analysis of the co-expressed genes was conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene-set enrichment analysis (GSEA). The correlation between FLT3 expression and tumor immune infiltration was jointly analyzed with estimate, ssGSEA, TIMER, and TISIDB. Then we employed checkpoint-related molecules, immunophenoscore (IPS), and tumor mutation burden (TMB) to assess the efficacy of immuno-checkpoint inhibitors (ICIs). Pearson correlation coefficient was employed to exam the association between DNA methylation and FLT3 expression. Results: FLT3 displays an elevated expression in breast cancer than normal pairs and is significantly associated with multiple clinical characteristics like age, menopause status, histological type, pathological stage, and molecular subtype as well as increased overall survival (OS). Additionally, FLT3 is a favorable independent prognostic factor. GO, KEGG, and GSEA suggested that FLT3 was associated with diversified immune-related features. FLT3 expression is correlated with the abundance of various immune cells namely CD4+T cell, CD8+ T cell, myeloid dendritic cell, and neutrophil as well as immune inhibitors especially CTLA4, which is positively correlated with FLT3 expression. Moreover, TMB displayed a negative correlation with FLT3 expression while IPS showed adverse tendency. Ultimately, the methylation of FLT3 downregulates the gene expression and closely binds to a few clinical parameters. Conclusion: FLT3 can be used for prognostic prediction and is relevant to immune infiltration in breast cancer. FLT3 may pave the way for future novel immunotherapies. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation between pre-ablation ultrasound radiomics features and the sonication energy for focused ultrasound surgery (FUS) of benign breast tumors. Method: 53 benign breast tumors of 28 patients treated by ultrasound-guided focused ultrasound surgery (USgFUS) were included in this study. The sonication energy per unit volume of each tumor was calculated. Three-quarter point was chosen as the cut-off to divide the 53 included tumors into high sonication energy (HSE, n = 14) and low sonication energy (LSE, n = 39) groups. For each tumor, the region of interest (ROI) of both the tumor itself (tROI) and the near field tissue (nfROI) were delineated and analyzed separately using ImageJ software. Pearson correlation coefficient and multiple linear regression analysis were used for radiomics feature selection. To explore the diagnostic performance of different ultrasound radiomics features, a receiver operating characteristic (ROC) curve analysis was performed. Results: In total of 68 radiomics features were extracted from pre-ablation ultrasound images of each tumor. Of all radiomics features, BX in tROI (p < 0.001), BX (p = 0.001) and Circ (p = 0.019) in nfROI were independently predictive features of sonication energy per unit volume. The ROC curves showed that the area under the curve (AUC) values of BX in tROI, BX, and Circ in nfROI were 0.797, 0.787 and 0.822, respectively. Conclusion: This study provided three radiomics features of pre-ablation ultrasound image as predictors of sonication dose for FUS in benign breast tumors. Further clinical trials are needed to confirm the predictive effect of these radiomics features. [ABSTRACT FROM AUTHOR]

Objective: To explore the learning curve of high intensity focus ultrasound (HIFU) treatment for breast fibroadenoma. Methods: 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. Results: The inflection points of the learning curves were the 60th treatment in Center 1 and the 65th treatment in Center 2. The screening time, treatment time, sonication time and hyperechoic scale change time were significantly shorter in consolidation phase than those in initial phase of the two centers (p < 0.05). There were no differences in non-perfused volume (NPV) ratio and energy effect factor (EEF) between the two groups in Center 1, while in Center 2, these above-mentioned results in consolidation phase led to a greater improvement than those in initial phase. There was no difference of Visual Analogue Scale (VAS) scores and no adverse event observed in both centers. Conclusion: HIFU 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. [ABSTRACT FROM AUTHOR]

Objective: To investigate the factors influencing the sonication dosage and efficiency of ultrasoundguided high intensity focused ultrasound (USgHIFU) for breast fibroadenomas. Materials and Methods: 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. Results: Fibroadenoma size, distance from the shallow margin of the fibroadenoma to skin and type of near field acoustic pathway had significant correlation with EEF (p < 0.05). An EEF (^y) dosimetry model of ^y¼ 0.496X1þ 0.287X2+ 0.203X3 was established, in which X1 stands for size of fibroadenoma, X2 stands for the distance from shallow margin of the fibroadenoma to skin, and X3 stands for type of near field acoustic pathway. The predicted EEF value was significantly related to actual EEF (R ¼ 0.698, p ¼ 0.000). Conclusions: 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. [ABSTRACT FROM AUTHOR]

QKI, a KH domain containing RNA binding, is an RNA-binding protein that is involved in cell proliferation and apoptosis through binding to the QKI response element (QRE) site of its target mRNA. And Caspase 8 (CASP8) and Caspase 3 (CASP3) play important roles in the pathway of apoptosis. The purpose of this study was to investigate the effect of QKI-5 on the apoptosis of Sertoli cells. The experimental results show that pig tissues contain QKI-5, QKI-6 and QKI-7. Overexpression of QKI-5 significantly decreased the mRNA expression of CASP8 (P < 0.05) and the protein expression of CASP8 (P < 0.05). On the contrary, inhibiting QKI-5 increased the expression of CASP8 significantly. Overexpression of QKI-5 significantly reduced the apoptosis of Sertoli cells and promoted cell growth (P < 0.05). Furthermore, QKI-5 specifically reduced the stability of CASP8 mRNA by binding QRE sites on CASP8. Our experiments provide preliminary evidence that QKI-5 induces Sertoli cells proliferation by inhibiting apoptosis, and this may be one of the factors promoting testicular development. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to screen and identify the target genes of miR-375 in pig Sertoli (ST) cells and to elucidate the effect of miR-375 on the proliferation of ST cells. Methods: In this study, bioinformatics software was used to predict and verify miR-375 target genes. Quantitative polymerase chain reaction (PCR) was used to detect the relationship between miR-375 and its target genes in ST cells. Enzyme-linked immunosorbent assay (ELISA) of rearranged L-myc fusion (RLF) and hypoxia-induced gene domain protein 1A (HIGD1A) was performed on porcine ST cells, which were transfected with a miR-375 mimics and inhibitor to verify the results. Dual luciferase reporter gene assays were performed to assess the interactions among miR-375, RLF, and HIGD1A. The effect of miR-375 on the proliferation of ST cells was analyzed by CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS). Results: Five possible target genes of miR-375, including RLF, HIGD1A, colorectal cancer associated 2, POU class 3 homeobox 1, and WW domain binding protein 1 like, were found. The results of quantitative PCR suggested that mRNA expression of RLF and HIGD1A had a negative correlation with miR-375, indicating that RLF and HIGD1A are likely the target genes of miR-375. The ELISA results revealed that RLF and HIGD1A were negatively correlated with the miR-375 protein level. The luminescence results for the miR-375 group cotransfected with wild-type RLF and HIGD1A vector were significantly lower than those of the miR-375 group co-transfected with the blank vector or mutant RLF and HIGD1A vectors. The present findings suggest that RLF and HIGD1A are target genes of miR-375 and that miR-375 inhibits ST cell proliferation according to MTS analysis. Conclusion: It was speculated that miR-375 affects cell proliferation through its target genes, which play an important role in the development of testicular tissue. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node biopsy (SLNB) is well accepted to be a standard procedure in breast cancer surgery with clinically negative lymph nodes. Isosulfan blue is the first dye approved by the USA Food and Drug Administration for the localization of the lymphatic system. Few alternative tracers have been investigated. In this study, we aimed to compare the differences between 10 % fluorescein sodium and 1 % isosulfan blue in breast sentinel lymph node biopsy and to investigate the feasibility of using 10 % fluorescein sodium as a new dye for breast sentinel lymph node biopsy. Methods: A total of 30 New Zealand rabbits were randomly divided into the fluorescein sodium group and the isosulfan blue group (15 rabbits per group). Fluorescein sodium or isosulfan blue was injected subcutaneously into the second pair of mammary areolas. Results: The average fading time of the second lymph nodes in the isosulfan blue group was significantly shorter than that in the fluorescein sodium group. Moreover, the detection rates of SLNs were higher in the fluorescein sodium group than in the isosulfan blue group. No significant differences between the fluorescein sodium group and isosulfan blue group were observed regarding the distances between the detected sentinel lymph nodes and second pair of mammary areolas, the distances between the second lymph nodes and second pair of mammary areolas, the number of detected sentinel lymph nodes and second lymph nodes, the average dyeing time of the sentinel and the second lymph nodes, and the average fading time of the second lymph nodes. Conclusions: In summary, we first reported that fluorescein sodium is a potential new tracer for breast sentinel lymph node biopsy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 < 0.001). Of these 167 breast cancer cases, a significantly higher rate (54/58) of intratumoral ALDH1 expression was observed in invasive cancer without EIC cases than that in DCIS cases (19/46, one case not available) and invasive cancer with EIC cases (27/60, two cases not available) (P < 0.001). Interestingly, a significantly higher rate (22/48) of intratumoral ALDH1 expression in invasive component was observed than that in in situ component (7/48) in the same tumor (P = 0.001). In 47 DCIS cases, no significant association was observed between ALDH1 positivity and any clinicopathological parameter (all 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 < 0.001), and high Ki67 expression (P = 0.009). Conclusions: ALDH1 may play an important role in the invasion of breast cancer, and may be associated with aggressive phenotypes of breast cancer. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1608671725154947. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]