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Background: Obesity and the forkhead box O1(FOXO1) affect the survival of breast cancer patients, but the underlying mechanism remains unclear. We aimed to investigate the role of FOXO1 in obesity-associated-breast cancer. Methods: We screened 383 breast disease patients from the first affiliated hospital with Nanjing Medical University in 2020. We performed wound healing, transwell, matrigel assays to assess the metastatic ability of cancer cells. We adopted mRNAs sequencing to select the differentially expressed transcripts in breast cancer. We applied immunohistochemistry, western blot, tissue microarrays to assess the level of FOXO1 and epithelial-mesenchymal transition (EMT) pathways. We conducted bioinformatic analysis to investigate interactions between FOXO1 and miR-135b. We used fluorescence in situ hybridization, RT-qPCR to confirm the characteristics of circCNIH4. We conducted luciferase reporter assay, rescue experiments to investigate interactions between circCNIH4 and miR-135b. Results: Obesity was positively correlated with the incidence and progression of breast cancer. Adipocytes enhanced the migration of breast cancer and attenuated the effects of FOXO1. MiR-135b was a binding gene of FOXO1 and was regulated by circCNIH4. CircCNIH4 exhibited antitumor activity in vitro and in vivo. Conclusion: Adipocytes might accelerate the progression of breast cancer by modulating FOXO1/miR-135b/ circCNIH4 /EMT axis and regulating copper homeostasis. [ABSTRACT FROM AUTHOR]

Temporal muscle thickness measured on 3D MRI has recently been linked to prognosis in glioblastoma patients and may serve as an independent prognostic indicator. This single-center study looked at temporal muscle thickness and prognosis in patients with primary glioblastoma. Overall survival was the major study outcome. For a retrospective analysis from 2010 to 2020, clinical data from 102 patients with glioblastoma at the Department of Oncology Radiotherapy of the First Affiliated Hospital of Dalian Medical University were gathered. Fifty-five cases from 2016 to 2020 contained glioblastoma molecular typing data, of which 45 were IDH wild-type glioblastomas and were analysed separately. TMT was measured on enhanced T1-weighted magnetic resonance images in patients with newly diagnosed glioblastoma.Overall patient survival (OS) was calculated by the Kaplan–Meier method and survival curves were plotted using the log-rank-sum test to determine differences between groups, and multifactorial analyses were performed using a Cox proportional-risk model.The median TMT for 102 patients was 6.775 mm (range: 4.95–10.45 mm). Patients were grouped according to median TMT, and the median overall survival (23.0 months) was significantly longer in the TMT > median group than in the TMT median group (P 0.001; Log-rank test). Analysing 45 patients with IDH wild type alone, the median overall survival (12 months) of patients in the TMT > median group was significantly longer than that of patients in the TMT ≤ median group (8 months) (P < 0.001; Log-rank test).TMT can serve as an independent prognostic factor for glioblastoma. [ABSTRACT FROM AUTHOR]

Purpose: Malignant phyllodes tumor of the breast (MPTB) is a rare type of breast cancer, with an incidence of less than 1%. The value of adjuvant radiotherapy (RT) for MPTB has been controversial. The aim of the study was to explore the effect of radiotherapy on the long-term survival of female patients with MPTB at different ages. Methods: Female MPTB patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020. A Kaplan–Meier survival analysis was conducted to investigate the value of RT for the long-term survival of MPTB patients in different age groups. Additionally, univariate and multivariate Cox regression analyses were performed for overall survival (OS) and breast cancer-specific survival (BCSS) of MPTB patients. Furthermore, propensity score matching (PSM) was also performed to balance the differences in baseline characteristics. Results: 2261 MPTB patients were included in this study, including 455 patients (20.12%) with RT and 1806 patients (79.88%) without RT. These patients were divided into four cohorts based on their ages: 18–45, 46–55, 56–65, and 65–80. Before adjustment, there was a statistically significant difference in long-term survival between RT-treated and non-RT-treated patients in the younger age groups (age group of 18–45 years: OS P = 0.019, BCSS P = 0.016; age group of 46–55 years: OS P < 0.001, BCSS P < 0.001). After PSM, no difference was found in long-term survival of patients in both younger and older groups regardless of whether they received RT (age group of 18–45 years: OS P = 0.473, BCSS P = 0.750; age group of 46–55 years: OS P = 0.380, BCSS P = 0.816, age group of 56–65 years: OS P = 0.484, BCSS P = 0.290; age group of 66–80 years: OS P = 0.997, BCSS P = 0.763). In multivariate COX regression analysis, RT did not affect long-term survival in patients with MPTB. Conclusion: There is no evidence that long-term survival of MPTB patients in specific age groups can benefit from RT. [ABSTRACT FROM AUTHOR]

The aberrant expression of microRNAs (miRNAs) is involved in the initiation and progression of human cancers. In our study, we found that miR-539 was down-regulated in breast cancer tissues and cell lines. Decreased expression of miR-539 was significantly associated with lymph node metastasis in patients with breast cancer. Overexpression of miR-539 inhibited the proliferation and promoted apoptosis of breast cancer cells. Moreover, highly expressed miR-539 significantly suppressed the epithelial-mesenchymal transition (EMT) and sensitized cells to cisplatin treatment. Mechanistically, miR-539 was found to target the specificity protein 1 (SP1) and down-regulated the expression of SP1 in breast cancer cells. Knockdown of miR-539 consistently increased the expression of SP1. The expression of miR-539 in breast cancer tissues was negatively correlated with the expression of SP1. Restoration of SP1 significantly attenuated the inhibitory effect of miR-539 on the proliferation of breast cancer cells. Taken together, our results indicate that miR-539 has a tumor suppressive role in breast cancer via targeting SP1, suggesting miR-539 as a promising target for the diagnosis of breast cancer. Key words: miR-539, breast cancer, SP1. L'expression anormale des microARN (miARN) a ete impliquee dans l'initiation et la progression des cancers chez l'humain. Les auteurs ont trouve ici que le miR-539 etait regule a la baisse dans les tissus et les lignees de cancer du sein. L'expression reduite du miR-539 etait significativement associee aux metastases ganglionnaires chez les personnes atteintes du cancer du sein. La surexpression du miR-539 inhibait la proliferation et favorisait l'apoptose des cellules de cancer du sein. De plus, le miR-539 fortement exprime reprimait significativement la transition epithelio-mesenchymateuse (TEM) et sensibilisait les cellules au traitement au cisplatine. D'un point de vue du mecanisme, le miR-539 s'est avere cibler la proteine SP1 (specificity protein 1) et reguler a la baisse l'expression de SP1 dans les cellules de cancer du sein. De la meme maniere, le knockdown du miR-539 augmentait l'expression de SP1. L'expression du miR-539 etait negativement correlee avec celle de SP1 dans les tissus de cancer du sein. Le retablissement de SP1 attenuait significativement l'effet inhibiteur du miR-539 sur la proliferation des cellules de cancer du sein. L'ensemble de ces resultats indiquait que le miR-539 exerce un role de suppresseur tumoral dans le cancer du sein en ciblant SP1, suggerant le miR-539 comme cible prometteuse dans le diagnostic du cancer du sein. [Traduit par la Redaction] Mots-cles : miR-539, cancer du sein, SP1., Introduction Breast cancer is the most common malignancy with high mortality among women worldwide (Fan et al. 2014; Kotsopoulos 2018). The conventional therapeutic approaches for breast cancer include surgical resection, [...]

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is correlated with poor prognosis, the current treatment of which is still based on surgery and adjuvant targeted therapy with monoclonal antibody. Problems of drug resistance hinder the use of monoclonal antibodies. Subsequently, tyrosine kinase inhibitors (TKIs) have been noticed, TKIs have the advantages of multi-targets and reduced drug resistance. However, TKIs that target HER family proteins often cause adverse effects such as liver damage and diarrhea. Thus, TKIs with high selectivity are being developed. TH-4000, a prodrug that generated an active form TH-4000Effector (TH-4000E) under hypoxic condition, was evaluated in this research. We found that TH-4000E ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium) (1–1000 nM) had potent and highly selective toxic effects on HER2+ breast cancer cells and inhibited the phosphorylation of HER family kinases at lower doses than that of Lapatinib and Tucatinib. TH-4000E activated Caspase-3 and induced apoptosis through a reactive oxygen species (ROS)-dependent pathway. The prodrug TH-4000 ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium;bromide) (50 mg/kg) effectively suppressed the tumor growth with less liver damage in mouse tumor models. This hypoxia-targeted strategy has possessed advantage in avoiding drug-induced liver damage, TH-4000 could be a promising drug candidate for the treatment of HER2+ breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is the most frequent malignant disease in women worldwide. It is a heterogeneous and complex genetic disease with different molecular characteristics. MAPT-AS1, a long non-coding RNA (lncRNA) existing at the anti-sense strand of the MAPT (microtubule associated protein tau) promoter region, was believed to regulate MAPT, which was associated with disease state in Parkinson's disease. But the role of MAPT-AS1 in breast cancer has never been reported. In our study we found that MAPT-AS1 is overexpressed in breast cancer but not in triple negative breast cancer (TNBC), and that high expression of MAPT-AS1 was correlated with better patient survival. In addition, the level of MAPT-AS1 was correlated with the expression of MAPT, and MAPT was associated with survival time in breast cancer. Our study suggests that MAPT-AS1 may play a role and be a potential survival predictive biomarker in breast cancer. Key words: breast cancer, MAPT-AS1, long non-coding RNA, patient survival. Le cancer du sein est l'affection maligne la plus frequente chez la femme a travers le monde. Il s'agit d'une maladie genetique heterogene et complexe qui presente differentes caracteristiques moleculaires. MAPT-AS1, un long ARN non codant (ARNnm) qui agit comme brin anti-sens dans la region du promoteur de la proteine associee aux microtubules MAPT (<< microtubule associated protein tau >>), est presume reguler MAPT qui a ete associee a la maladie de Parkinson. Toutefois, le role de MAPT-AS1 dans le cancer du sein n'a jamais ete rapporte. Les auteurs ont trouve dans cette etude que MAPT-AS1 est surexprime dans le cancer du sein, mais pas dans le cancer du sein triple negatif, et qu'une expression elevee de MAPT-AS1 etait correlee a une meilleure survie chez les patientes. De plus, le niveau de MAPT-AS1 etait correle avec celui de MAPT, associee a la duree de vie dans lecancer dusein. Leur etude suggere que MAPT-AS1 peut jouerun role dansle cancer du seinet agir commeunpotentiel biomarqueur predictif de la survie. [Traduit par la Redaction] Mots-cles : cancer du sein, MAPT-AS1, long ARN non codant, survie des patientes., Introduction Breast cancer is the most malignant cancer in females and it is estimated that approximately 252 710 new cases of invasive breast cancer are expected to be diagnosed in [...]