Occult breast cancer patients with mastectomy have better prognosis than those with breast-conserving therapy.

Background: This single-center retrospective study compared the efficacy of breast-conserving therapy along with axillary lymph node dissection (ALND) with mastectomy and ALND with regard to survival of Chinese patients with occult breast cancer. Materials & methods: Univariate Kaplan-Meier analysis and multivariate Cox proportional hazards model were used to compare treatments and prognosis. Results: A total of 111 patients with a median follow-up of 72.9 months were included. 39 patients with mastectomy + ALND had better disease-free survival than 72 patients with breast-conserving therapy + ALND (HR = 0.31; p = 0.012). Patients with radiotherapy demonstrated inferior survival for both overall survival (HR = 2.67; p = 0.071) and disease-free survival (HR = 5.35; p = 0.002). Surgical strategies and radiotherapy remained significantly predictive of better disease-free survival in multivariate analyses. Conclusion: Mastectomy and ALND demonstrate superior disease-free prognosis compared with breast-conserving therapy and ALND in occult breast cancer.

Enhancing the photodegradation of tetracycline in aquaculture wastewater via iron(III)-alginate: Degradation pathway transformation and toxicity reduction.

Tetracycline's (TC) incomplete self-photolysis by light irradiation generally produces toxic intermediate products, which posing serious harm to the aqueous environment. In order to diminish the environmental risks of TC self-photolysis, an iron(III)-alginate (Fe-SA) hydrogel assisted photocatalytic method was developed and the underlying mechanisms was also analyzed in this work. Under simulated sunlight, the photo-degradation efficiency of TC was 61.1% at pH 7.0 within 2 h. Importantly, four of the seven intermediate products that identified during the self-photolysis of TC were found toxic based on QSAR analysis. In contrast, the removal efficiency of TC could be improved to 87.4% by adding Fe-SA under the same conditions. Moreover, only two relatively weakly toxic intermediate products were detected after exposing to the Fe-SA photocatalytic system, indicating a significant reduction of the potential ecological risks caused by TC self-photolysis. Furthermore, the determination of reactive oxidation species (ROS) demonstrated that the addition of Fe-SA primarily facilitated the degradation of TC and the related toxic intermediate products through assisting the free radical (∙OH and ∙O2-) photocatalytic degradation pathway. Additionally, the photocatalytic application under actual sunlight conditions and the reusability experiments of Fe-SA further confirmed its effectiveness and low cost in removing TC. This study revealed the photodegradation mechanisms of TC from the perspective of the self-photolysis process, and also offering new insights into the removal of TC pollution in the environment.

[Preparation of porous boron nitride-doped polypyrrole-2,3,3-trimethylindole solid-phase microextraction coating for polycyclic aromatic hydrocarbon detection].

Most polycyclic aromatic hydrocarbons (PAHs), which are persistent organic pollutants, have strong carcinogenicity, teratogenicity, and mutagenicity, and pose serious threats to the ecological environment and human health. Owing to the complexity of the matrix and low PAH content of environmental samples, separating and enriching PAHs in environmental samples is necessary prior to their detection. Solid-phase microextraction (SPME) technology is commonly used to detect PAHs owing to its advantages of simple operation, online connection with other instruments, low solvent usage, and integrability of sampling separation, enrichment, and desorption. The extraction coating is the core of this technology, and the type and thickness of the coating are important factors affecting the sensitivity and accuracy of the analysis. Common commercial extraction coatings include polydimethylsiloxane and quartz fiber; however, these materials have a number of disadvantages, such as poor thermal stability and high cost. Several methods, including electrochemical, sol-gel, molecular imprinting, and other coating methods, have been developed to prepare SPME coatings. Electrochemical methods have attracted considerable attention because of their simplicity, short duration, and high coating stability. In the development of an electrochemical method, the selection of the conductive polymer is of particular importance. Polypyrroles (Ppy) are easily synthesized and have numerous advantages, such as good conductivity and stable chemical properties. Thus, their use as a substrate material for SPME coatings is beneficial for improving the overall stability of the coating. Copolymerization with other polymers can enhance the adsorption performance of such coatings via synergistic effects. When doped with inorganic materials with high thermal stability, the composite coating can exhibit high temperature resistance. In this study, a porous boron nitride-doped Ppy-2,3,3-trimethylindole (Ppy/P2,3,3-TMe@In/BN) composite was prepared as a new SPME copolymer coating to detect three PAHs: naphthalene (NAP), acenaphthene (ANY), and fluorene (FLU). Scanning electron microscopy, thermal stability analysis, Fourier transform infrared spectroscopy, and other techniques were used to characterize the Ppy/P2,3,3-TMe@In/BN composite coating. The results showed that the coating featured a large number of porous and wrinkled dendritic structures, which increased the specific surface area of the composite coating and enabled the extensive enrichment of the three PAHs. When the sample inlet temperature of the chromatograph is 320 ℃, the chromatographic baseline of the coating is basically stable. Compared with commercial coatings, the prepared coating had better thermal stability. The coating formed stable intermolecular forces with the three PAHs owing to its numerous carbon-carbon double bonds (C=C), hydrogen bonds, and other structures, thereby achieving excellent enrichment of the target analytes. Compared with Ppy, Ppy/PIn, Ppy/P2,3,3-TMe@In, Ppy/BN, and polydimethylsiloxane (PDMS) coatings, the prepared Ppy/P2,3,3-TMe@In/BN composite coating exhibited better extraction effects for the three PAHs. The Ppy/P2,3,3-TMe@In/BN composite coating was polymerized on the surface of a stainless-steel wire by cyclic voltammetry and combined with gas chromatography-hydrogen flame ionization detection (GC-FID) to optimize the conditions influencing the extraction and separation of the three PAHs, thereby establishing a highly sensitive analytical method for detecting NAP, ANY, and FLU. This method had low limits of detection (LODs) of 10.6-14.5 ng/L (S/N=3) and high stability. The SPME-GC-FID method was used to detect the three PAHs in two environmental water samples, and a small amount of ANY (1.39 µg/L) was detected in one water sample. Satisfactory recoveries (82.5%-113.9%) were obtained when both water samples were spiked with the three PAHs at three levels. The experimental results indicate that the established analytical method can detect the three PAHs in environmental water samples.

The value of postcontrast delayed 3D fluid-attenuated inversion recovery MRI in the diagnosis of unilateral peripheral vestibular dysfunction.

Background: Clinically, unilateral peripheral vestibular dysfunction (UPVD) with dizziness or vertigo as the chief complaint is quite common. This study aimed to investigate the correlations between 3-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI) findings and cochleovestibular function test results in patients with UPVD and to explore the possible etiologies of UPVD. Methods: This retrospective study enrolled 76 patients with UPVD. Endolymphatic hydrops (EH) and perilymphatic enhancement (PE) in the vestibule and cochlea on 3D-FLAIR images, their correlations with the parameters of the cochleovestibular function test and vascular risk factors, and the immunological findings of patients with EH and PE were assessed. Results: Of the included patients, 48.7% showed positive MRI findings (the presence of EH and PE on 1 side). The pure-tone average (PTA) was higher in patients with cochlear PE than in those with vestibular (P=0.014) and cochlear EH (P=0.02). The canal paresis (CP) value was also higher in patients with vestibular PE than in those with vestibular (P=0.002) and cochlear EH (P=0.003). Video head impulse test (vHIT) gains were lower in patients with vestibular and cochlear PE than in those with vestibular and cochlear EH (P<0.001). A positive correlation was observed between the degree of vestibular and cochlear EH and PTA (both P values <0.001). PTA and CP with a cutoff value of 32 dB and 46.5%, respectively, yielded high sensitivity and specificity in determining positive MRI findings (P<0.001 and P=0.029, respectively). The prevalence of vascular risk factors was significantly higher in patients with PE than in those with EH (P=0.033). Conclusions: (I) Nearly half of the patients UPVD exhibited abnormal MRI findings. Cutoff values for PTA and CP of 32 dB and 46.5%, respectively, indicated that patients were more likely to have abnormal imaging findings. (II) The severity of EH was positively correlated with hearing impairment. (III) Patients with PE showed severe hearing impairment and vestibular dysfunction, which was presumed to be associated with vascular damage.

[Somatic Mutations of Acquired Aplastic Anemia].

Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are clonal diseases with hemopoietic stem cell (HSC) abnormalities,which are sometimes difficult to be distinguished from each other.The development of molecular detection techniques has facilitated our understanding of the molecular pathogenesis of the two diseases.This article reviewed the somatic mutation (SM) and cytogenetic changes of AA,and analyzed their molecular relationship with MDS and their roles in disease transformation.The most common somatic change in AA is the loss of PIGA and HLA alleles,which,along with trisomy 8 and del(13q),is related to the immune pathogenesis of AA.Among the 5 most common mutations in AA,PIGA and BCOR/BCORL1 mutations are related to a good prognosis,while DNMT3A and ASXL1 mutations are likely associated with clonal evolution and a poor prognosis.The risk factors for secondary MDS after AA include SM and cytogenetic changes such as del(7q) associated with poor prognosis,prolonged disease duration after diagnosis,onset age of AA,and leukocyte telomere attrition.Although role of SM in disease progression remains unclear because of its dynamic change and unknown significance,prognostic assessment based on the monitoring of SM and clinical features may guide the treatment.

DrABC: deep learning accurately predicts germline pathogenic mutation status in breast cancer patients based on phenotype data.

BACKGROUND: Identifying breast cancer patients with DNA repair pathway-related germline pathogenic variants (GPVs) is important for effectively employing systemic treatment strategies and risk-reducing interventions. However, current criteria and risk prediction models for prioritizing genetic testing among breast cancer patients do not meet the demands of clinical practice due to insufficient accuracy. METHODS: The study population comprised 3041 breast cancer patients enrolled from seven hospitals between October 2017 and 11 August 2019, who underwent germline genetic testing of 50 cancer predisposition genes (CPGs). Associations among GPVs in different CPGs and endophenotypes were evaluated using a case-control analysis. A phenotype-based GPV risk prediction model named DNA-repair Associated Breast Cancer (DrABC) was developed based on hierarchical neural network architecture and validated in an independent multicenter cohort. The predictive performance of DrABC was compared with currently used models including BRCAPRO, BOADICEA, Myriad, PENN II, and the NCCN criteria. RESULTS: In total, 332 (11.3%) patients harbored GPVs in CPGs, including 134 (4.6%) in BRCA2, 131 (4.5%) in BRCA1, 33 (1.1%) in PALB2, and 37 (1.3%) in other CPGs. GPVs in CPGs were associated with distinct endophenotypes including the age at diagnosis, cancer history, family cancer history, and pathological characteristics. We developed a DrABC model to predict the risk of GPV carrier status in BRCA1/2 and other important CPGs. In predicting GPVs in BRCA1/2, the performance of DrABC (AUC = 0.79 [95% CI, 0.74-0.85], sensitivity = 82.1%, specificity = 63.1% in the independent validation cohort) was better than that of previous models (AUC range = 0.57-0.70). In predicting GPVs in any CPG, DrABC (AUC = 0.74 [95% CI, 0.69-0.79], sensitivity = 83.8%, specificity = 51.3% in the independent validation cohort) was also superior to previous models in their current versions (AUC range = 0.55-0.65). After training these previous models with the Chinese-specific dataset, DrABC still outperformed all other methods except for BOADICEA, which was the only previous model with the inclusion of pathological features. The DrABC model also showed higher sensitivity and specificity than the NCCN criteria in the multi-center validation cohort (83.8% and 51.3% vs. 78.8% and 31.2%, respectively, in predicting GPVs in any CPG). The DrABC model implementation is available online at http://gifts.bio-data.cn/ . CONCLUSIONS: By considering the distinct endophenotypes associated with different CPGs in breast cancer patients, a phenotype-driven prediction model based on hierarchical neural network architecture was created for identification of hereditary breast cancer. The model achieved superior performance in identifying GPV carriers among Chinese breast cancer patients.

Murine models of rosacea: a review.

Rosacea is a chronic inflammatory disease characterized by facial flushing, erythema, telangiectasia, papules, and pustules. Its pathogenesis has not been fully understood. In 2017, the global ROSacea COnsensus (ROSCO) panel updated the diagnosis, classification, and assessment of rosacea. Phenotype-based treatments and long-term managements have also been recommended. Murine models are a powerful tool in unveiling and dissecting the mechanisms of human diseases. Here, we summarized murine models of rosacea developed or used in previous research, including LL-37 intradermal injection model, KLK-5-induced inflammation model, croton oil inflammation model, 12-O-Tetradecanoylphorbol-13-acetate inflammation model, arachidonic acid inflammation model, RTX-induced vasodilation model, and UVB-induced model. LL-37 injection model has become the most intensively used model in rosacea research. Each model could show the pathophysiological and clinical features of rosacea to some extent. However, no model can show the full picture of the characteristics of rosacea. Improving existed murine models, developing new murine models, and applying them to pathogenesis and treatment research on rosacea are highly warranted in the future.

Overexpression of IncRNA SAMMSON Promotes Triple-Negative Breast Cancer Cell Proliferation by Interacting with p53.

This study was carried out to explore the role of the long noncoding RNA (lncRNA) SAMMSON in triple-negative breast cancer (TNBC). The research patients in this study included 68 TNBC patients. Cell Counting Kitcck-8 were utilized to determine cell proliferation abilities, respectively. Proteins and mRNAs were estimated by western blot and Methylation-specific polymerase chain reaction, respectively. We found that SAMMSON was upregulated, while p53 was downregulated in cancer (TNBC) tissues than in non-cancer tissues of TNBC patients. SAMMSON expression levels in TNBC tissues increased with the increase of clinical stages of TNBC patients. SAMMSON and p53 were inversely correlated in TNBC tissues. In TNBC cells, SAMMSON overexpression decreased p53 expression, while p53 overexpression failed to affect SAMMSON expression. In addition, SAMMSON overexpression increased TNBC cell proliferation, while p53 overexpression decreased the proliferation rates of TNBC cells. In addition, p53 overexpression attenuated the effects of SAMMSON overexpression. Therefore, overexpression of SAMMSON could promote TNBC cell proliferation by interacting with p53.

Contralateral risk-reducing local therapy in breast cancer patients with BRCA1/2 mutations: systemic review and meta-analysis.

BACKGROUND: Unilateral breast cancer (UBC) patients with germline pathogenic BRCA1/2 variants have a higher risk of developing contralateral breast cancer (CBC) and need contralateral risk-reducing local treatments, including contralateral risk-reducing mastectomy (CRRM) and prophylactic irradiation (CPI). The aim of our study was to systematically explore the efficacy of CRRM and CPI in reducing CBC risk and increasing survival. METHODS: A search was done, and eligible randomized trials and cohort studies should include and compare UBC patients with germline pathogenic BRCA1/2 variants who have and have not received contralateral risk-reducing local treatment. Random-effects meta-analysis was used in this study. Primary outcomes of the studies included overall survival (OS) and the incidence of contralateral breast cancer (CBC), and secondary outcomes included breast cancer-specific survival (BCSS). RESULTS: A total of five studies with 1769 UBC patients with germline pathogenic BRCA1/2 variants were enrolled in our meta-analysis. CRRM was correlated with a lower risk of CBC in UBC patients with germline pathogenic BRCA1/2 variants (summary RR = 0.07; 95%CI 0.03-0.13, I2 = 3%), a significantly increased OS (summary RR, 1.15; 95%CI 1.04-1.26, I2 = 26%) and a significantly increased BCSS (summary RR, 1.18; 95%CI 1.07-1.31, I2 = 64%) compared with surveillance. CPI also decreased the risk of CBC (RR 0.02; 95%CI 0.05-0.88) but did not significantly improve OS (RR 0.97; 95%CI 0.90-1.05) and BCSS (RR 0.97; 95%CI 0.90-1.05) compared with surveillance. CONCLUSIONS: CRRM reduces CBC risk and increases OS and BCSS in UBC patients with germline pathogenic BRCA1/2 variants, and could be offered as a risk-reducing local treatment. For those who oppose CRRM, CPI could be offered for CBC-risk reduction, while its survival benefit is still uncertain.

The Distinct Performances of Ultrasound, Mammograms, and MRI in Detecting Breast Cancer in Patients With Germline Pathogenic Variants in Cancer Predisposition Genes.

A proportion of up to 10% of breast cancer resulted from hereditary germline pathogenic variants (GPVs) in cancer predisposition genes (CPGs), which been demonstrated distinct clinical features and imaging manifestations. However, the performance of imaging modalities for breast cancer surveillance in CPG mutation-carriers is still unclear, especially in Asian women. A population of 3002 breast cancer patients who received germline genetic testing of CPGs was enrolled from three hospitals in China. In total, 343 (11.6%) patients were found to harbor GPVs in CPGs, including 137 (4.6%) in BRCA1 and 135 (4.6%) in BRCA2. We compared the performances of ultrasound, mammograms, MRI, and the combining strategies in CPG mutation carriers and non-carriers. As a result, the ultrasound showed a higher detection rate compared with mammograms regardless of the mutation status. However, its detection rate was lower in CPG mutation carriers than in non-carriers (93.2% vs 98.0%, P=2.1×10-4), especially in the BRCA1 mutation carriers (90.9% vs 98.0%, P=2.0×10-4). MRI presented the highest sensitivity (98.5%) and the lowest underestimation rate (14.5%) in CPG mutation carriers among ultrasound, mammograms, and their combination. Supplemental ultrasound or mammograms would add no significant value to MRI for detecting breast cancer (P>0.05). In multivariate logistic regression analysis, the family or personal cancer history could not replace the mutation status as the impact factor for the false-negative result and underestimation. In summary, clinicians and radiologists should be aware of the atypical imaging presentation of breast cancer in patients with GPVs in CPGs.

CircRNA circ-PDCD11 promotes triple-negative breast cancer progression via enhancing aerobic glycolysis.

Well-described evidence has demonstrated the critical roles of aerobic glycolysis in triple-negative breast cancer (TNBC) oncotherapy. Moreover, next-generation high-throughput sequencing indicates the potential regulation of energy metabolism by circular RNAs (circRNAs) in TNBC. However, circRNA modulation of TNBC aerobic glycolysis is still unclear. Here, the present research aimed to investigate the function and underlying mechanisms of novel circPDCD11 (hsa_circ_0019853) in TNBC aerobic glycolysis. The results revealed that circPDCD11 expression was significantly upregulated in TNBC tissues and cells. Clinical data demonstrated that the high expression of circPDCD11 was closely correlated with a poor prognosis and acted as an independent risk factor for TNBC prognosis. Functionally, in vitro gain- and loss-of-function experiments revealed that circPDCD11 accelerated glucose uptake, lactate production, ATP generation, and the extracellular acidification rate in TNBC cells. In vivo, circPDCD11 silencing repressed tumor growth. Mechanistically, circPDCD11 acted as a miRNA sponge to enhance LDHA expression by sponging miR-432-5p. In conclusion, these combined results demonstrated that circPDCD11 acts as an oncogene for TNBC, providing a promising prognostic biomarker for TNBC.

Effect of MiR-210 on the Chemosensitivity of Breast Cancer by Regulating JAK-STAT Signaling Pathway.

The study is aimed at exploring the effect of microribonucleic acid- (miR-) 210 on the chemosensitivity of breast cancer and its potential molecular mechanism. Cell Counting Kit-8 (CCK-8) was applied to detect the half maximal inhibitory concentration (IC50) of cisplatin (DDP) on cell, and quantitative polymerase chain reaction (qPCR) was carried out to measure the relative expression level of miR-210. The IC50 value of DDP on cells was detected via CCK-8 after downregulating the expression of miR-210 in MCF-7/DDP cells. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) confirmed the effect of themiR-210 downregulation on the apoptosis of drug-resistant MCF-7/DDP cells. Besides, the impacts of the miR-210 downregulation on apoptosis-related proteins and Janus-activated kinase- (JAK-) signal transducer and activator of transcription (STAT) signaling pathway-related proteins were examined by Western blotting. The interaction between miR-210 and the target protein was detected through luciferase activity assay, qPCR, and Western blotting. Drug-resistant MCF-7/DDP cells had significantly stronger resistance to DDP and a remarkably higher expression level of miR-210 than control parental MCF-7 cells (p < 0.05). After the downregulation of the miR-210 expression, MCF-7/DDP cells had markedly reduced resistance but obviously increased sensitivity to DDP (p < 0.05). MiR-210 downregulation increased the apoptosis of MCF-7/DDP cells (p < 0.05). In addition, after miR-210 was knocked down, the expression level of b-cell lymphoma 2 (Bcl-2) was decreased, while the expression levels of Bcl-2-associated X protein (Bax) and cysteinyl aspartate-specific proteinase-3 (caspase-3) were increased. Besides, miR-210 was able to suppress the expression of protein inhibitor of the activated STAT 4 (PIAS4) gene by directly targeting its 3' untranslated region (3'UTR). The expression of miR-210 has a correlation with chemoresistance of breast cancer MCF-7 cells. MiR-210 regulates the JAK-STAT signal transduction pathway by targeting PIAS4, thus exerting an effect on breast cancer chemosensitivity.

Effects of Ulinastatin on Proliferation and Apoptosis of Breast Cancer Cells by Inhibiting the ERK Signaling Pathway.

PURPOSE: To explore the effects of ulinastatin on the proliferation and apoptosis of breast cancer cells and the relevant mechanism of action. METHODS: Breast cancer cells (MCF-7) were cultured and randomly divided into three groups, namely, control group, ulinastatin group, and ulinastatin+extracellular-regulated protein kinase (ERK) inhibitor group. Then, the Cell Counting Kit-8 (CCK-8) assay was carried out to detect the effect of ulinastatin on the viability of breast cancer cells. The effects of ulinastatin on the proliferation and apoptosis of breast cancer cells were determined via EdU staining and Hoechst 33258 staining assays, respectively. The messenger ribonucleic acid (mRNA) and protein expression levels of ERK and forkhead box O3 (FOXO3) in breast cancer cells were measured through reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: In comparison with the control group, the ulinastatin group displayed decreased viability of breast cancer cells, a decreased positive rate of 5-ethynyl-2'-deoxyuridine (EdU) staining, an increased positive rate of Hoechst 33258 staining, and reduced mRNA and protein levels of ERK and FOXO3 in breast cancer cells. Compared with those in the ulinastatin group, the viability of breast cancer cells was lowered, the positive rate of EdU staining was reduced, the positive rate of Hoechst 33258 staining was raised, and the mRNA and protein levels of ERK and FOXO3 in breast cancer cells clearly declined in the ulinastatin+ERK inhibitor group. CONCLUSION: Ulinastatin inhibits the proliferation and promotes the apoptosis of breast cancer cells. The possible mechanism of action is associated with the suppression of the ERK signaling pathway.

Anti-vascular endothelial growth factor therapy in breast cancer: Molecular pathway, potential targets, and current treatment strategies.

As the highest incidence of female malignancy, breast cancer is likewise the leading cause of cancer-related deaths. The development of cancer relies on neo-vascularization, which provides sufficient nutrition and oxygen, and supplies a pathway for distant metastasis. Angiogenesis represents the formation of new blood vessels, and is a principal pathogenetic action in breast cancer. Vascular endothelial growth factor (VEGF) is a major angiogenesis regulator that modulates the maintenance and function of mature vascular networks. Therefore, the VEGF pathway is a promising oncotherapeutic target. This review elaborates an update on the prognostic value of VEGF in breast cancer, summarizes clinical experience and lessons of anti-VEGF therapeutics, meanwhile, provides an overview of biomarkers that predict the effectiveness of anti-angiogenic treatment.

LINC00337 induces tumor development and chemoresistance to paclitaxel of breast cancer by recruiting M2 tumor-associated macrophages.

BACKGROUND: M2 tumor-associated macrophages are closely related to the progression and prognosis of breast cancer (BCa), and could be regulated by long intergenic non-coding RNAs (lincRNAs). Moreover, the differential expression of lincRNAs affects tumor resistance. This study focused on the potential involvement and mechanism of LINC00337 in BCa. METHODS: The expression of LINC00337 in BCa was detected by bioinformatics analysis and RT-qPCR. Cell viability and proliferation were analyzed by cell counting kit-8 (CCK-8) and clone formation assay. BCa cells were treated with different concentrations of paclitaxel (PAX) to determine the chemotherapy resistance of LINC00337. Tumor formation assay, Western blot, ELISA and immunohistochemistry were performed to determine the relationship between LINC00337 and PAX in vivo. Macrophages were induced to M2-like polarization, and then functional experiments (CCK-8, wound healing) and molecular experiments (ELISA, RT-qPCR, Western blot) were used to verify the role of LINC00337. RESULTS: LINC00337 was up-regulated in BCa. High-expressed LINC00337 accelerated viability and proliferation of BCa cells, improved the resistance of BCa cells to PAX, and accelerated tumor growth. Overexpressed LINC00337 up-regulated the expressions of M2 macrophage markers and M-CSF, and reduced the level of GM-CSF. PAX significantly reduced the viability of BCa cells and down-regulated LINC00337. Furthermore, the successfully induced M2 type macrophages to promote BCa cell activity, migration and EMT protein expression, and LINC00337 enhanced the effect of M2 type macrophages. ShLINC00337 had the opposite effect to overexpressed LINC00337. CONCLUSION: LINC00337 accelerated the malignant phenotype of BCa cells and promoted chemoresistance to paclitaxel through M2-like macrophages.

Circulating exosomal miR-363-5p inhibits lymph node metastasis by downregulating PDGFB and serves as a potential noninvasive biomarker for breast cancer.

Sentinel lymph node (LN) biopsy is currently the standard procedure for clinical LN-negative breast cancer (BC) patients but it is prone to false-negative results and complications. Thus, an accurate noninvasive approach for LN staging is urgently needed in clinical practice. Here, circulating exosomal microRNA (miRNA) expression profiles in peripheral blood from BC patients and age-matched healthy women were obtained and analyzed. We identified an exosomal miRNA, miR-363-5p, that was significantly downregulated in exosomes from plasma of BC patients with LN metastasis which exhibited a consistent decreasing trend in tissue samples from multiple independent datasets. Plasma exosomal miR-363-5p achieved high diagnostic performance in distinguishing LN-positive patients from LN-negative patients. The high miR-363-5p expression level was significantly correlated with improved overall survival. Functional assays demonstrated that exosomal miR-363-5p modulates platelet-derived growth factor (PDGF) signaling activity by targeting PDGFB to inhibit cell proliferation and migration. Our study revealed, for the first time, plasma exosomal miR-363-5p plays a tumor suppressor role in BC and has the potential for noninvasive LN staging and prognosis prediction of BC.

Silencing of Nek2 suppresses the proliferation, migration and invasion and induces apoptosis of breast cancer cells by regulating ERK/MAPK signaling.

Breast cancer is a frequent cancer among women. The current study investigated the biological functions of Nek2 in breast cancer and its possible mechanism. The mRNA expression of Nek2 in breast epithelial cells and eight breast cancer cell lines was detected by qRT-PCR. Silencing Nek2 was transfected into MDA-MB-231 and MCF7 cells to examine its roles in the viability, migration, invasion, cell colony, apoptosis and cell cycle of the breast cancer cells by performing CCK-8, wound scratch, Transwell, clone formation and flow cytometry assays, respectively. The expressions of related genes were detected using qRT-PCR and Western blot. MAPK pathway agonist IGF (insulin-like growth factor-1) was added into MDA-MB-231 and MCF7 cells and then cell viability was examined. Nek2 expression was frequently up-regulated in breast cancer cell lines, and silencing Nek2 significantly inhibited the viability, cell migration, invasion and clone formation, promoted cell apoptosis of MDA-MB-231 and MCF7 cells, and arrested cell cycle in G0/G1 phase. Furthermore, knocking down Nek2 decreased the mRNA and protein expressions of Bcl-2, CyclinB1 and CyclinD1, and increased Bax and p27 expressions. Moreover, knocking down Nek2 inhibited the phosphorylation of ERK and p38, and almost completely reversed the expression of p-ERK increased by IGF, but Nek2 knockdown had no obvious effect on p-p38. The inhibitory effect of Nek2 silencing on the cell viability was mainly realized by the inhibition of ERK/MAPK signaling. Nek2 plays an important role in the regulation of the progression of breast cancer in vitro probably through regulating the ERK/MAPK signaling.

Expression and prognostic value of CDK1, CCNA2, and CCNB1 gene clusters in human breast cancer.

OBJECTIVE: Cell cycle-associated proteins play important roles in breast cancer (BRCA), based on evidence from cell lines, preclinical murine models, and human tissue samples. METHODS: Herein, we used the Onomine, GEPIA, Kaplan-Meier Plotter, and cBioPortal databases to examine transcriptional and survival data pertaining to cyclin-associated gene clusters (CDK1, CCNA2, and CCNB1) in BRCA patients. RESULTS: CDK1, CCNA2, and CCNB1 gene expression levels were higher in BRCA compared with control tissue samples and were correlated with more-advanced tumor stage. Kaplan-Meier survival analyses confirmed that elevated CDK1, CCNA2, and CCNB1 expression levels were associated with overall and post-progression survival and recurrence-free probability rates in patients with BRCA. CONCLUSION: The results of this study implied that CDK1, CCNA2, and CCNB1 gene clusters may provide potential therapeutic targets and prognostic biomarkers in patients with BRCA.

Cost-Effectiveness Analysis of Imaging Modalities for Breast Cancer Surveillance Among BRCA1/2 Mutation Carriers: A Systematic Review.

BACKGROUND: BRCA1/2 mutation carriers are suggested with regular breast cancer surveillance screening strategies using mammography with supplementary MRI as an adjunct tool in Western countries. From a cost-effectiveness perspective, however, the benefits of screening modalities remain controversial among different mutated genes and screening schedules. METHODS: We searched the MEDLINE/PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases to collect and compare the results of different cost-effectiveness analyses. A simulated model was used to predict the impact of screening strategies in the target group on cost, life-year gained, quality-adjusted life years, and incremental cost-effectiveness ratio (ICER). RESULTS: Nine cost-effectiveness studies were included. Combined mammography and MRI strategy is cost-effective in BRCA1 mutation carriers for the middle-aged group (age 35 to 54). BRCA2 mutation carriers are less likely to benefit from adjunct MRI screening, which implies that mammography alone would be sufficient from a cost-effectiveness perspective, regardless of dense breast cancer. CONCLUSIONS: Precision screening strategies among BRCA1/2 mutation carriers should be conducted according to the acceptable ICER, i.e., a combination of mammography and MRI for BRCA1 mutation carriers and mammography alone for BRCA2 mutation carriers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42020205471.

Hsa_circ_0069094 accelerates cell malignancy and glycolysis through regulating the miR-591/HK2 axis in breast cancer.

Circular RNAs (circRNAs) are implicated in the initiation and advancement of diverse tumors. CircRNA hsa_circ_0069094 (circ_0069094) has been reported to be upregulated in BC, but the biological role of circ_0069094 in BC is indistinct. Hence, we aimed to survey the biological role of circ_0069094 in BC. In the present study, we verified that circ_0069094 was upregulated in BC tissues and cells. BC patients with high circ_0069094 expression had a poor prognosis. Functional analysis revealed that circ_0069094 silencing induced apoptosis, curbed proliferation, and reduced glycolysis in BC cells in vitro, but circ_0069094 overexpression had an opposing influence. Also, circ_0069094 knockdown reduced BC growth in vivo. Mechanically, circ_0069094 was validated as a decoy for miR-591, which targeted HK2. Importantly, circ_0069094 sponged miR-591 to regulate HK2 expression. Both miR-591 silencing and HK2 overexpression counteracted circ_0069094 inhibition-mediated influence on cell proliferation, apoptosis, and glycolysis in BC cells. In conclusion, these results indicated that circ_0069094 facilitated cell malignancy and glycolysis by upregulating HK2 through adsorbing miR-591, suggesting that circ_0069094 might be a prognostic biomarker and therapeutic target for BC.