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Inflammation has been confirmed to be closely related to the development of tumors, while peroxynitrite (ONOO - ) is one of the most powerful oxidative pro-inflammatory factors. Although ONOO - can kill bacteria through oxidation, it will activate matrix metalloproteinases (MMPs), accelerate the degradation of the extracellular matrix (ECM), and subsequently lead to the activation and release of other tumor promotion factors existing in the ECM, promoting tumor metastasis and invasion. Herein, we report a simple aggregation-induced emission (AIE) nanoprobe (NP), TPE-4NMB, that can simultaneously visualize and deplete ONOO - . The probe can light up the endogenous and exogenous ONOO - in cells and selectively inhibit the proliferation and migration of 4T1 cells by inducing an intracellular redox homeostasis imbalance through ONOO - depletion. After being modified with DSPE-PEG 2000 , the TPE-4NMB NPs can be used to image ONOO - induced by various models in vivo; especially, it can monitor the dynamic changes of ONOO - level in the residual tumor after surgery, which can provide evidence for clarifying the association between surgery, ONOO - , and cancer metastasis. Excitingly, inhibited tumor volume growth and decreased counts of lung metastases were observed in the TPE-4NMB NPs group, which can be attributed to the downregulated expression of MMP-9 and transforming growth factor-β (TGF-β), increased cell apoptosis, and inhibited epithelial-mesenchymal transition (EMT) mediated by ONOO - . The results will provide new evidence for clarifying the relationship between surgery, ONOO - , and tumor metastasis and serve as a new intervention strategy for preventing tumor metastasis after tumor resection.

Background: Despite advancements, breast cancer outcomes remain stagnant, highlighting the need for precise biomarkers in precision medicine. Traditional TNM staging is insufficient for identifying patients who will respond well to treatment., Methods: Our study involved over 6,900 breast cancer patients from 14 datasets, including in-house clinical data and single-cell data from 8 patients (37,451 cells). We integrated 10 machine learning algorithms in 55 combinations and analyzed 100 existing breast cancer signatures. IHC assays were conducted for validation, and potential immunotherapies and chemotherapies were explored., Results: We pinpointed six stable Panoptosis-related genes from multi-center cohorts, leading to a robust Panoptosis-model. This model outperformed existing clinical and molecular features in predicting recurrence and mortality risks, with high-risk patients showing worse outcomes. IHC validation from 30 patients confirmed our findings, indicating the model's broader applicability. Additionally, the model suggested that low-risk patients benefit more from immunotherapy, while high-risk patients are sensitive to specific chemotherapies like BI-2536 and ispinesib., Conclusion: The Panoptosis-model represents a major advancement in breast cancer prognosis and treatment personalization, offering significant insights for effectively managing a wide range of breast cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, Hou, Li, Ni and Wang.)

DNA repair is a vital mechanism in cells that protects against DNA damage caused by internal and external factors. It involves a network of signaling pathways that monitor and transmit damage signals, activating various cellular activities to repair DNA damage and maintain genomic integrity. Dysfunctions in this repair pathway are strongly associated with the development and progression of cancer. However, they also present an opportunity for targeted therapy in breast cancer. Extensive research has focused on developing inhibitors that play a crucial role in the signaling pathway of DNA repair, particularly due to the remarkable success of PARP1 inhibitors (PARPis) in treating breast cancer patients with BRCA1/2 mutations. In this review, we summarize the current research progress and clinical implementation of BRCA and BRCAness in targeted treatments for the DNA repair pathway. Additionally, we present advancements in diverse inhibitors of DNA repair, both as individual and combined approaches, for treating breast cancer. We also discuss the clinical application of DNA repair-targeted therapy for breast cancer, including the rationale, indications, and summarized clinical data for patients with different breast cancer subtypes. We assess their influence on cancer progression, survival rates, and major adverse reactions. Last, we anticipate forthcoming advancements in targeted therapy for cancer treatment and emphasize prospective areas of development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Drug resistance in breast cancer (BC) is a clinical challenge. Exploring the mechanism and identifying a precise predictive biomarker for the drug resistance in BC is critical. Three first-line drug (paclitaxel, doxorubicin and tamoxifen) resistance datasets in BC from GEO were merged to obtain 1,461 differentially expressed genes for weighted correlation network analysis, resulting in identifying ATRX as the hub gene. ATRX is a chromatin remodelling protein, therefore, ATRX-associated transcription factors were explored, thereby identifying the network of AR, GLI3 and GATA2. GO and KEGG analyses revealed immunity, transcriptional regulation and endocrinotherapy/chemotherapy resistance were enriched. Moreover, CIBERSORT revealed immunity regulation was inhibited in the resistance group. ssGSEA showed a significantly lower immune status in the ATRX-Low group compared to the ATRX-High group. Furthermore, the peaks of H3K9me3 ChIP-seq on the four genes were higher in normal tissues than in BC tissues. Notably, the frequency of ATRX mutation was higher than BRCA in BC. Moreover, depressed ATRX revealed worse overall survival and disease-free survival in the human epidermal growth factor receptor 2 (HER2)-/hormone receptor (HR)+ BC. Additionally, depressed ATRX predicted poor results for patients who underwent endocrinotherapy or chemotherapy in the HER2-/HR+ BC subgroup. A nomogram based on ATRX, TILs and ER exhibited a significantly accurate survival prediction ability. Importantly, overexpression of ATRX significantly inhibited the IC 50 of the three first-line drugs on MCF-7 cell. Thus, ATRX is an efficient predictive biomarker for endocrinotherapy and chemotherapy resistance in HER2-/HR+ BC and acts by suppressing the AR, GLI3 and GATA2 transcriptional network.

Breast cancer is the leading cause of cancer-related death among females, which is required to be solved urgently. Recent studies have found significant changes in a large number of genes and their transcriptional levels during breast cancer development, which are often closely related to the abnormal expression of long noncoding RNAs (lncRNAs). Herein, our study found that MBNL1-AS1 was down-regulated both in breast cancer tissues and cell lines, and it functioned as a tumor suppressor to inhibit cancer cell proliferation, migration, and invasion. MiR-423-5p was found to be a target of MBNL1-AS1 with an inverse relationship: an increase in miR-423-5p could counteract the inhibitory effect induced by MBNL1-AS1 on cancer cell promotion. Further, CREBZF was negatively regulated by miR-423-5p. Accordingly, CREBZF knockdown could impair the hindrance of cancer cell growth mediated by low miR-423-5p expression. Also, MBNL1-AS1 influenced the PI3K/AKT pathway, which was associated with cell proliferation and apoptosis, by regulating CREBZF. As a result, our work illustrated the tumor suppressor role of MBNL1-AS1 in breast cancer via upregulating miR-423-5p-targeted CREBZF. Thereby, the evidence indicates the complete understanding of the role of MBNL1-AS1/miR-423-5p/CREBZF axis in the regulation of breast cancer development, which could be used as a biomarker for predicating survival among breast cancer patients.

Introduction: The aim of the study was to explore the feasibility of performing sentinel lymph node biopsy (SLNB) using a carbon nanoparticle suspension (CNPS) after neoadjuvant chemotherapy in breast cancer patients., Methods: Some 152 patients diagnosed with primary breast cancer (cT1-3N0-2M0) were recruited. Patients were divided into two groups according to axillary lymph node (ALN) status after four to six cycles of neoadjuvant chemotherapy. All patients received a CNPS injection, after which SLNB and axillary lymph node dissection (ALND) were performed., Results: Sentinel lymph nodes (SLN) of 143 patients were identified; with an accuracy rate of 94.4% and a false-negative rate of 9.9%. Group A included 67 patients, and the detection, accuracy and false-negative rates within this group were 95.5%, 96.9% and 6.7%, respectively. The corresponding rates for group B (85 patients) were 92.9%, 92.4% and 11.8%, respectively., Conclusions: CNPS is an ideal tracer for improving the detection rate of SLN and can be used to determine SLN status following neoadjuvant chemotherapy.

Erythropoietin‑producing hepatocellular receptors (Ephs) comprise the largest subfamily of receptor tyrosine kinases and have been reported to be involved in a variety of biological cellular processes, including tumorigenesis and cancer progression. The present study aimed to determine the expression levels and clinicopathological significance of EphA8 in breast cancer (BC) using immunohistochemistry analysis of tissue microarrays. The results of the present study revealed that EphA8 expression levels were upregulated in BC tissue and were associated with tumor size and TNM stage. In addition, upregulated expression levels of EphA8 were identified to be a poor prognostic biomarker for patients with BC. The knockdown of EphA8 expression using short hairpin RNA resulted in increased levels of apoptosis as well as decreased proliferation, migration and invasion of BC cells both in vivo and in vitro . The knockdown of EphA8 also decreased the phosphorylation of AKT, which was accompanied by downregulation of Bcl‑2 expression levels and upregulation of p53, Caspase‑3 and Bax expression levels. Moreover, knockdown of EphA8 expression increased the chemosensitivity of BC cells to paclitaxel. In conclusion, the results of the present study indicated that EphA8 may be a useful prognostic marker in BC and that knockdown of EphA8 may represent a novel strategy in adjuvant chemotherapy for the treatment of BC.

Background: The physical and psychological well-being of patients with breast cancer is an important global issue. Acceptance and commitment therapy (ACT) aims to equip patients with the skills to respond and adapt to difficult circumstances. However, the extent of the physical and psychological outcomes of this therapy in patients with breast cancer remains unclear., Objectives: The aim of the study was to summarize available evidence and assess the efficacy of ACT on physiological and psychological outcomes in patients with breast cancer., Methods: Published randomized controlled studies were identified in MEDLINE, PsycInfo, Embase, Web of Science, CINAHL, and CNKI from inception to December 2019 and Cochrane Library, AMED, and Clinical trials.gov from inception to September 2020. Methodological rigor was assessed by two reviewers using the Cochrane Handbook for Systematic Review of Interventions. Sufficient data were statistically pooled with review manager; otherwise, a narrative summary was used., Results: Thirteen trials were included in the review. Methodological quality varied across the studies. Meta-analyses demonstrated that ACT had moderate to large effects on reducing anxiety, depression, and stress and improving hope. Sensitivity analyses reached results similar to those of the meta-analyses. However, the effects of ACT on the physiological symptoms, fear of cancer recurrence, and psychological flexibility of patients with breast cancer remain inconclusive., Discussion: ACT has beneficial effects on the anxiety, depression, stress, and hope of patients with breast cancer. The evidence of ACT on physiological symptoms, fear of cancer recurrence, and psychological flexibility needs to be treated with caution. Further studies are needed and should consider different delivery forms and also explore the mechanisms of each component of ACT under different cultural contexts., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Accumulating evidence suggests that intrinsic resistance to radiotherapy reduces the survival of patients with cancer. The present study investigated whether miR-93-5p affects proliferation, migration, apoptosis, and radiosensitivity of breast cancer (BC) cells. MDA-MB-468, MCF-7, and MDA-MB-231 BC cells were incubated with hsa-miR-93-5p mimics, hsa-miR-93-5p inhibitor, and negative control RNA with or without exposure to ionizing radiation to determine cell proliferation, migration, and apoptosis using the Cell Counting Kit-8 assay, wound healing assay and apoptotic assay, respectively. Overexpression of miR-93-5p inhibited the migratory abilities (P = 0.001) and decreased the cell proliferation (P = 0.049) of MCF-7 cells. In MCF-7 cells, a significant increase in apoptosis was detected after treatment with miR-93-5p compared with the negative control (P = 0.001) and miR-93-5p inhibitor (P = 0.004). In MDA-MB-468 cells, the proportion of apoptotic cells increased following exposure to ionizing radiation (P = 0.001). The percentage of apoptotic MDA-MB-231 cells in the miR-93-5p group was significantly increase compared with that determined in the negative control (P = 0.044) and hsa-miR-93-5p inhibitor (P = 0.046) groups. In conclusion, our findings showed that miR-93-5p reduces BC cell proliferation and migratory capacity, and increases the ratio of apoptotic cells. Overexpression of miR-93-5p could increase radiosensitivity in BC cells by increasing apoptosis. This evidence provides new insight into the treatment of BC and identifies miR-93-5p as a potential therapeutic target.

Supersensitive magnetic resonance (MR) imaging requires contrast with extremely high r 2 values. However, synthesized magnetic nanoparticles generally have a relatively low r 2 relaxivity. Magnetosomes with high saturation magnetization and good biocompatibility have shown potential values as MR imaging contrast agents. Magnetosomes that target human epidermal growth factor receptor-2 (HER2) were prepared using genetic technology and low-frequency sonication. Anti-HER2 affibody of the ability to target HER2 was displayed on the membrane surface of the magnetosomes through the anchor protein MamC, allowing the bacterial nanoparticles to target tumors overexpressing HER2. The prepared nanoparticles exhibited a very high relaxivity of 599.74 mM -1 s -1 and better dispersion, and their ability to target HER2 was demonstrated both in vitro and in vivo. Also, the HER2-targeting magnetosomes significantly enhanced the MR imaging of orthotopic breast cancer models with or without HER2 expression using a 7.0 T scanner. In particular, tumors overexpressing HER2 demonstrated better MR imaging than HER2-negative tumors after intravenous administration of HER2-targeting magnetosomes, and the MR signals of the augmented contrast could be detected from 3 to 24 h. The magnetosomes did not cause any notable pathogenic effect in the animals. Therefore, we expect that noninvasive imaging of tumors using HER2-targeting magnetosomes has potential for clinical applications in the near future.

Loading of microRNAs (miRNAs) into exosomes that are involved in cellular communication is a selective process. The current study investigates whether the enrichment of miRNAs in exosomes reflects the pathogenesis of breast cancer (BC) and ductal carcinoma in situ (DCIS). The levels of miRNAs were quantified in exosomes from plasma of 32 BC patients, 8 DCIS patients and 8 healthy women by TaqMan real-time PCR-based miRNA array cards containing 47 different miRNAs. Then, exosomal miR-16, miR-30b and miR-93 that displayed deregulation in the arrays were selected and analyzed in 111 BC patients, 42 DCIS patients and 39 healthy women by TaqMan real-time PCR. Identification of exosomes was performed by Western blot. The levels of exosomal miR-16 were higher in plasma of BC (p = 0.034) and DCIS (p = 0.047) patients than healthy women, and were associated with estrogen (p = 0.004) and progesterone (p = 0.008) receptor status. Particularly, in estrogen-positive patients miR-16 was significantly enriched in exosomes (p = 0.0001). Lower levels of exosomal miR-30b were associated with recurrence (p = 0.034). Exosomal miR-93 was upregulated in DCIS patients (p = 0.001). Our findings suggest that different signatures of miR-16, miR-30b and miR-93 in exosomes from BC and DCIS patients are associated with a particular biology of breast tumors.

Breast cancer is the second leading cause of cancer‑associated mortality in women worldwide. Strong evidence has suggested that Ran, which is a small GTP binding protein involved in the transport of RNA and protein across the nucleus, may be a key cellular protein involved in the metastatic progression of cancer. The present study investigated Ran gene expression in breast cancer tissue samples obtained from 140 patients who had undergone surgical resection for breast cancer. Western blot analysis of Ran in breast cancer tissues and paired adjacent normal tissues showed that expression of Ran was significantly increased in breast cancer tissues. Immunohistochemistry analyses conducted on formalin‑fixed paraffin‑embedded breast cancer tissue sections revealed that Ran expression was associated with tumor histological grade, nerve invasion and metastasis, vascular metastasis and Ki‑67 expression (a marker of cell proliferation). Kaplan‑Meier survival analysis showed that increased Ran expression in patients with breast cancer was positively associated with a poor survival prognosis. Furthermore, in vitro experiments demonstrated that highly migratory MDA‑MB‑231 cancer cells treated with Ran‑si‑RNA (si‑Ran), which knocked down expression of Ran, exhibited decreased motility in trans‑well migration and wound healing assays. Cell cycle analysis of Ran knocked down MDA‑MB‑231 cells implicated Ran in cell cycle arrest and the inhibition of proliferation. Furthermore, a starvation and re‑feeding (CCK‑8) assay was performed, which indicated that Ran regulated breast cancer cell proliferation. Taken together, the results provide strong in vitro evidence of the involvement of Ran in the progression of breast cancer and suggest that it could have high potential as a therapeutic target and/or marker of disease.

Breast cancer (BC) is one of the most fatal diseases and poses critical health problems worldwide. However, its mechanisms remain unclear. Consequently, there is an urgency to investigate the mechanisms involved in BC initiation and progression and identify novel therapeutics for its prevention and treatment. In this study, we identified karyopherin β-1 (Kpnβ1) as a possible novel therapeutic target for BC. Western blotting was used to evaluate the expression of Kpnβ1 in four pairs of tumorous and adjacent non-tumorous tissues. The results revealed that the protein level of Kpnβ1 was higher in the cancer samples compared with those in the corresponding normal samples. Immunohistochemistry was performed on 140 BC cases and indicated that Kpnβ1 was significantly associated with clinical pathological variables. Kaplan-Meier curve revealed that high expression of Kpnβ1 was related to poor BC patient prognosis. A starvation and re-feeding assay was used to imitate the cell cycle using the SKBR-3 cell line, indicating that Kpnβ1 plays a critical role in cell proliferation. The Cell Counting Kit-8 assay revealed that SKBR-3 cells treated with Kpnβ1-siRNA (siKpnβ1) grew more slowly than the control cells, while flow cytometry revealed that low-Kpnβ1 expressing SKBR-3 cells exhibited increased BC cell apoptosis. Furthermore, the interaction between Kpnβ1 and Her2 was clearly observed by immunoprecipitation, indicating that Kpnβ1-knockdown abrogated nuclear transport of Her2. In summary, our findings revealed that Kpnβ1 is involved in the progression of BC and may be a useful therapeutic target.

Objective: To explore the expression of latent transforming growth factor (TGF)-beta binding protein 2 (LTBP2) in breast cancer and its clinical significance. Methods: Immunohistochemistry was used to detect the expression of LTBP2 in 125 cases of breast cancer tissue and normal breast tissue. Relationship between the expression of LTBP2 and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67, and its relationship with clinicopathological parameters of breast cancer were analyzed. Results: The positive expression of LTBP2 in breast cancer tissues (55.20%) was significantly higher than that in adjacent normal breast tissues (28.80%) ( P <0.001). The expression of LTBP2 in breast cancer tissues was correlated with the clinical stage (χ(2)=4.516, P =0.034), over-expression of ER (χ(2)=7.112, P =0.008) and Ki67(χ(2)=4.024, P =0.045) and other adverse prognostic factors. Conclusion: Positive expression of LTBP2 in breast cancer plays an important role in the development and progression of breast cancer, and may be a marker of prognosis of patients.

Background and Purpose: Limited information is available regarding the correlations between mammographic calcifications and the epidemiological features of patients with breast cancer living different lifestyles in Western China. Thus, this study aimed to investigate the relationship between mammographic calcifications and the epidemiological characteristics of female patients with breast cancer in Western China., Methods: This was a hospital-based, retrospective, multi-center epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group (WCCCG) database, we obtained the records of 7317 patients (with mammographic data) diagnosed with breast cancer between March 2011 and June 2016. These patients were divided into Groups I (mass alone) and II (mass combined with calcification), and their clinical and pathological data were compared., Results: A total of 4211 patients were enrolled in Group I, and 3106 patients were enrolled in Group II. The tumors in Group II were more likely to be larger (P < 0.0001), higher grade (P = 0.0029), estrogen receptor (ER)+/progesterone receptor (PR)- (P = 0.0319), and human epidermal growth factor receptor 2 (HER-2)-positive (P < 0.0001), and to have axillary lymph node metastasis (P = 0.0033) than those in Group I. Regarding treatment, patients in Group II were more likely to have undergone chemotherapy (P = 0.0108) and anti-HER2 therapy (P = 0.0102), whereas patients in Group I were more likely to have undergone endocrine therapy (P < 0.0001)., Conclusions: In conclusion, mammographic calcifications in tumors were associated with distinct clinicopathologic characteristics and aggressive treatments.

Dyrk1B, also called minibrain-related kinase (Mirk), is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (Dyrk)/minibrain family of dual-specificity protein kinases. It is a serine/threonine kinase involved in the regulation of tumor progression and cell proliferation. In this study, the role of Dyrk1B in breast cancer development was investigated. The expression of Dyrk1B was detected by Western blot and immunohistochemistry staining, both of which demonstrated that Dyrk1B was overexpressed in breast cancer tissues and cells. Statistical analysis showed that the extent of Dyrk1B expression was associated with multiple clinicopathologic factors, including tumor size, grade, estrogen receptor status, and Ki-67 expression, and that high expression predicted a poor prognosis. The growth of breast cancer cells was inhibited significantly after knockout of DYRK1B by small interfering RNA (siRNA). Moreover, FoxO1 could be phosphorylated by Dyrk1B, and then FoxO1 was shuttled from the cell nucleus into the cytoplasm, which might be the mechanism of Dyrk1B-mediated survival in breast cancer cells. The results suggest that Dyrk1B plays a key role in the progression of breast cancer and provides a new target for breast cancer therapy., (Copyright © 2017. Published by Elsevier Inc.)

Mesenchymal stem cells (MSCs) are promising vehicles for the delivery of anticancer agents in cancer therapy. However, the tumor targeting of loaded therapeutics is essential. Here, we explored a dual-targeting strategy to incorporate tumor-tropic MSC delivery with HER2-specific killing by the immunoapoptotin e23sFv-Fdt-tBid generated in our previous studies. The MSC engineering allowed simultaneous immunoapoptotin secretion and bioluminescence detection of the modified MSCs. Systemic administration of the immunoapoptotin-engineered MSCs was investigated in human HER2-reconstituted syngeneic mouse models of orthotopic and metastatic breast cancer, as well as in a xenograft nude mouse model of orthotopic gastric cancer. In vivo dual tumor targeting was confirmed by local accumulation of the bioluminescence-imaged MSCs and persistence of His-immunostained immunoapoptotins in tumor sites. The added tumor preference of MSC-secreted immunoapoptotins resulted in a significantly stronger antitumor effect compared with purified immunoapoptotins and Jurkat-delivered immunoapoptotins. This immunoapoptotin-armored MSC strategy provides a rationale for its use in extended malignancies by combining MSC mobility with redirected immunoapoptotins against a given tumor antigen., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Growing evidence has demonstrated that human epidermal growth factor receptor 2 (HER2) is involved in the radiation response to breast cancer. However, the underlying mechanism remains elusive. Therefore, we investigated if HER2 overexpression is associated with radiosensitivity of breast cancer. We constructed breast cancer cell lines differing in HER2 expression by transducing HER2 cDNA or short hairpin RNA against HER2. We then assessed the radiosensitivity and investigated the potential mechanism by using cell proliferation assay, cell adhesion assays, anoikis assays, colony formation assays, and western blotting analyses. We found that HER2 introduction in breast cancer cell lines MCF-7 (low HER2 expression) and MDA-MB-231 (HER2 is not expressed) promoted cell proliferation and invasion and enhanced cell adhesion and resistance to anoikis. Moreover, HER2 reduced radiosensitivity in these two cells compared with the corresponding control. The opposite results were observed when HER2 was silenced in breast cancer cell lines ZR-7530 and SK-BR-3 (both cells with high expression of HER2) using HER2 shRNA. In addition, animal experiment results showed HER2 could enhance the radioresistance of xenograft tumors. Further studies showed HER2 promoted the phosphorylation of focal adhesion kinase (Fak) and thereby up-regulated the expression of proteins associated with the epithelial-to-mesenchymal transition such as Claudin-1, ZO-1, and ZEB-1. The inhibition of Fak activity using the Fak inhibitor (PF-562281) restored the radiosensitivity in HER2-overexpressing cells. In conclusion, HER2 reduces the radiosensitivity of breast cancer by activating Fak in vitro and in vivo. Fak might be a potential target for the radiosensitization of HER2-overexpressed breast cancer., Competing Interests: The authors declare no conflicts of interest.

Background and Aims: We undertook this study to investigate the influence of PIRH2 (p53-induced RING-H2) protein on the proliferation and cell cycle of breast cancer cell lines., Methods: PIRH2 expression was detected by Western blot analysis, immunohistochemistry (IHC) and Kaplan-Meier curve analysis. Cell proliferation was assessed by cell counting kit-8 (CCK-8). Cell cycle control was analyzed by flow cytometry., Results: PIRH2 was up-regulated in breast cancer tissues and cell lines and up-regulated PIRH2 was highly associated with tumor size, grade, ER, and Ki-67. Moreover, Kaplan-Meier curve showed that up-regulated PIRH2 was related to the poor overall survival of patients with breast carcinoma. When the expression of PIRH2 was inhibited by siRNA transfection, cell proliferation was reduced. In addition, the number of G0/G1 phase cells was increased, but G2/M cells were not affected significantly., Conclusion: Decrease of PIRH2 expression in the breast cancer cell line MDA-MB-231 resulted in reduced tumor cell growth via the inhibition of cell proliferation and the interruption of cell cycle transition., (Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.)

PFTK1 was a cell division cycle 2-related serine/threonine protein kinase, which was up-regulated in breast cancer tissues and breast cancer lines. And up-regulated PFTK1 was highly associated with grade, axillary lymph node status, and Ki-67. Moreover, Kaplan-Meier curve showed that up-regulated PFTK1 was related to the poor breast carcinoma patients' overall survival. Here, we first discovered and confirmed that cyclin B was a new interacting protein of PFTK1, and the complex might increase the amount of DVL2, which triggers Wnt/β-catenin signaling pathway. Furthermore, knockdown of PFTK1 attenuated cell proliferation, anchorage-independent cell growth, and cell migration and invasion by inhibiting the transcriptional activation of β-catenin for cyclin D1, MMP9, and HEF1, whereas exogenous expression of PFTK1 might promote MDA-MB-231 cells proliferation, migration, and invasion via promoting PFTK1-DVL2-β-catenin axis. Our findings supported the notion that up-regulated PFTK1 might promote breast cancer progression and metastasis by activating Wnt signaling pathway through the PFTK1-DVL2-β-catenin axis.

Objective: To examine the expression and prognostic value of novel oncogene Emi1 in breast cancer., Methods: Immunohistochemical analysis was performed for 93 human breast carcinoma samples and adjacent normal tissues for detecting the expression of Emi1 and cell proliferative factor Ki-67. Then the data were correlated with clinicopathological features., Results: Emi1 was highly expressed in breast carcinoma tissues compared with adjacent normal tissues. Emi1 expression was significantly associated with histological grade (P = 0.002) , axillary lymph node status (P = 0.017) and ER status (P = 0.038) . However, there was no correlation between Emi1 expression and other factors such as age, tumor size, histology, PR status, HER-2 or P53. Meanwhile similar results were obtained for Ki-67 expression. A marked correlation also existed between Emi1 and Ki-67 expression (Spearman's r² = 0.454, P = 0.002) ., Conclusion: As a novel breast cancer associated gene, Emil plays an important role in evaluating invasion and metastatic potentiality in breast cancer. And it is also an important prognostic predictor of breast cancer so as to become a potential therapeutic target for breast cancer.

Ski-interacting protein (SKIP) is a nuclear hormone receptor-interacting cofactor, interactions with the proto-oncogene Ski, appears to modulate a number of signalling pathways involved in control of cell proliferation and differentiation, and may play a critical role in oncogenesis. In the present study, to investigate the potential roles of SKIP in breast cancer, expression patterns, interaction and the correlation with clinical/prognostic factors of SKIP and Ki-67 were examined among patients with breast cancer. Immunohistochemistry and Western blot analysis were performed for SKIP in 85 breast carcinoma samples. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance. We found that SKIP was over expressed in breast carcinoma as compared with the adjacent normal tissues. High expression of SKIP was positively associated with histological grade (P = 0.01) and Ki-67 (P = 0.004). Univariate analysis showed that SKIP expression was associated with a poor prognosis (P = 0.006). While in vitro, following release of breast cancer cell lines from serum starvation, the expression of SKIP was up-regulated, whereas p27 was down-regulated. In addition, we employed small interfering RNA (siRNA) technique to knock down SKIP expression and observed it effects on MDA-MB-231 cells growth. SKIP depletion by siRNA inhibited cell proliferation, blocked S phase and decreased cyclin A and cyclin B levels. On the basis of these results, we suggested that SKIP overexpression was involved in the pathogenesis of breast cancer, which might serve as a future target for breast cancer.

Objective: To assess the appropriateness of breast cancer screening technologies in Guizhou province., Methods: We conducted a questionnaire survey, physical examinations, and high-frequency color Doppler ultrasound examinations in 20 183 women from 2010 to 2012 in Guizhou province. Biopsy was performed in those with suspected breast cancers., Results: The participants included 12,089 women who received repeated screening and 8,094 women who were given the screening service for the first time. Ten from the former group were identified with breast cancer (82.7/100 thousand), with the majority (80%) at an early stage. Eleven from the latter group were identified with breast cancer (135.9/100 thousand), 36.4% of whom being at an early stage. This resulted in a detection of 104 per 100 thousand breast cancers, with 57.1% at an early stage (0, I stage). The age of the women with breast cancer ranged from 35 to 80 years old. The prevalence peaked at 41-60 years of age, with 71.4% (15/21) falling into this age group (P < 0.05). Solid and cystic masses were found in 246 participants, with a minimum mass of 0.2 cm x 0.3 cm. Of the 228 participants diagnosed with benign masses, 225 (98.7%) were confirmed by biopsy results. The biopsy also confirmed 6 precancerous lesions., Conclusion: Guizhou had a prevalence of breast cancer of 104/100 thousand, which peaked at 41-60 years old. The screening method used in this study is appropriate.

S-phase kinase protein 2 (Skp2) is oncogenic and overexpressed in human breast cancer. The objective of this study was to examine the effect of early mitotic inhibitor-1 (Emi1) over-expression on Skp2 expression and related signaling pathway in breast cancer. Immunohistochemical analysis was performed in 98 human breast carcinoma samples and the data were correlated with clinicopathologic features. Furthermore, Western blot analysis was performed for Emi1 and Skp2 in breast carcinoma samples and cell lines to evaluate their protein levels and molecular interaction. We found that the expression of Emi1 was positively related with Skp2 expression (P < 0.01) and Emi1 expression correlated significantly with histologic grade (P = 0.005), meanwhile Skp2 expression obtained similar results. Kaplan-Meier analysis revealed that survival curves of low versus high expressers of Emi1 and Skp2 showed a highly significant separation in human breast cancer (P < 0.01). While in vitro, following release of breast cancer cell lines from serum starvation, the expression of Emi1, Skp2, phosphor-Akt (p-Akt) was up-regulated, whereas p27(Kip1) was down-regulated. Treatment of phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 could arrest cells growth and diminish Emi1 expression. These results suggested that Emi1's anti-apoptotic and proliferative abilities appear to be triggered at least in part by the modulation of Skp2, combined Emi1 and Skp2 expressions, may be prognostic for patients with invasive breast carcinomas, which also associated with p-Akt and enabled p27(kip1) degradation. Emi1 may serve as a potential therapeutic strategy aimed at PI3K for the management of breast cancer.

The prognosis of breast cancer patients with metastases is generally poor, so it is essential to elucidate related molecules mechanisms. Forkhead Box J2 (FOXJ2) is a member of Forkhead Box transcription factors, many of which have been reported to participate in tumor migration and invasion. In this study, we showed the expression of FOXJ2 was higher in primary breast cancer tissues without lymph nodes metastases than those with, and there was statistical significance between the expression of FXOJ2 and the clinical factors. Hence, we identified a novel function of metastasis, which was not previously known for FOXJ2. Overexpression of FOXJ2 decreased the motility property of highly migrative MDA-MB-231 cells in vitro by wound healing assays and trans-well migration assays, and it was concurrent with the increased expression of epithelial marker E-cadherin and the decreased expression of mesenchymal marker vimentin by Western blot analysis, reverse transcription PCR analysis, and immunofluorescence analysis. Consistent with these observations, the repression of FOXJ2 in weakly metastatic MCF-7 cells remarkably promoted cellular motility. Our study demonstrates that FOXJ2 can inhibit the metastasis of human breast cancer by regulating the EMT key markers E-cadherin and vimentin., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: To investigate the association of Caspase3 (CASP3) polymorphisms with susceptibility of breast cancer in Chinese Han population., Methods: In this population-based case-control study, 251 cases with breast cancers and 251 matched controls in terms of habitation and age (±5 years) were recruited. Rs4647693, rs2696056, rs4647610 were selected as TagSNPs in CASP3 gene and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The haplotype distribution was estimated and compared by PHASE software., Result: There was significant association between menarche age and breast cancer (P=0.007), as well as the early pregnancy age and breast cancer (P=0.002). No significant differences were detected in the distribution of CASP3 genotype and haplotype frequencies between breast cancer patients and controls. The GGA was the most common haplotype both in cases and controls., Conclusion: CASP3 polymorphisms and its haplotypes were not related to the susceptibility of breast cancer.

Objective: To investigate the expression of glucose transporter 1 (Glut1) in human breast cancer and its relationship to proliferating cell nuclear antigen (PCNA) protein, other tumor biomarkers and clinical pathologic factors., Methods: Imunohistochemical staining (SP) was applied to measure the expression of Glut1 and PCNA in 20 cases of human breast fibroadenoma, 20 cases of usual hyperplasia and 80 cases of breast carcinoma., Results: Glut1 was not found expressing in breast fibroadenoma and hyperplastic lesions. In contrast, the total positive rate of Glut1 in breast carcinoma was 58.8% (47/80); that in the ductal carcinoma in situ (DCIS) was 45.0% (9/20), that in the well-differentiated invasive carcinoma was 50.0% (15/30) and that in the poorly differentiated was 76.7% (23/30). The total positive rate of PCNA in breast carcinoma was 75% (60/80), that in DCIS was 65% (13/20) and that in invasive carcinoma was 78.3% (47/60). There was a positive correlation between Glut1 and PCNA level (r = 0.742, P (< 0.01)., Conclusion: The overexpression of Glut1 play important roles in carcinogenesis and progression of breast carcinoma and closely correlate with cell proliferation of breast carcinoma, may suggest different therapeutic approaches or the need for closer follow-up, and be wished to become a new target for treatment of breast carcinoma.