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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 [...]

Background: Hematological parameters have been associated with prognosis in patients with nasopharyngeal carcinoma (NPC). The present meta‐analysis investigated the utility of neutrophil‐lymphocyte ratio (NLR) in the prognosis of patients with NPC. Methods: Multiple electronic databases, including PubMed, Embase, the Cochrane Library, and the Web of Science, were systematically searched for studies assessing the association between NLR and NPC from 2011 to 2021. The primary outcomes were overall survival (OS) and progression‐free survival (PFS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized to estimate effect size. Use of a fixed effect or random effect model was based on heterogeneity stability was tested by sensitivity analysis, and the risk of bias was assessed by funnel plots. Random effects models were used based on the actual results. Because the NLR grouping criteria for the included studies differed, subgroup analyses were performed. Results: A search of the electronic databases identified 14 studies, encompassing 6693 patients, that met the selection criteria. NLR higher than the cutoff value was significantly associated with poorer OS [HR 1.760, 95% CI 1.470–2.120, p <0.00001] and PFS [HR 1.850, 95% CI 1.430–2.390, p =.006]. Sensitivity analysis showed that the results of the meta‐analysis were relatively stable, and funnel plots were used to exclude the risk of bias. Conclusions: Elevated pretreatment NLR in peripheral blood is predictive of poorer OS and PFS in patients with NPC. NLR is an easily measured and important prognostic factor in patients with NPC. [ABSTRACT FROM AUTHOR]

As an emerging imaging technique, thoracic ultrasonography (TUS) is increasingly utilized in the diagnosis of lung diseases in children and newborns, especially in emergency and critical settings. This systematic review aimed to estimate the diagnostic accuracy of TUS in childhood pneumonia. We searched Embase, PubMed, and Web of Science for studies until July 2023 using both TUS and chest radiography (CR) for the diagnosis of pediatric pneumonia. Two researchers independently screened the literature based on the inclusion and exclusion criteria, collected the results, and assessed the risk of bias using the Diagnostic Accuracy Study Quality Assessment (QUADAS) tool. A total of 26 articles met our inclusion criteria and were included in the final analysis, including 22 prospective studies and four retrospective studies. The StataMP 14.0 software was used for the analysis of the study. The overall pooled sensitivity was 0.95 [95% confidence intervals (CI), 0.92–0.97] and the specificity was 0.94 [95% CI, 0.88–0.97], depicting a good diagnostic accuracy. Our results indicated that TUS was an effective imaging modality for detecting pediatric pneumonia. It is a potential alternative to CXR and a follow-up for pediatric pneumonia due to its simplicity, versatility, low cost, and lack of radiation hazards. [ABSTRACT FROM AUTHOR]

Background. Non-small cell lung cancer (NSCLC) is the most prevalent malignant tumor of the lung cancer, for which the molecular mechanisms remain unknown. In this study, we identified novel biomarkers associated with the pathogenesis of NSCLC aiming to provide new diagnostic and therapeutic approaches for NSCLC by bioinformatics analysis. Methods. From the Gene Expression Omnibus database, GSE118370 and GSE10072 microarray datasets were obtained. Identifying the differentially expressed genes (DEGs) between lung adenocarcinoma and normal samples was done. By using bioinformatics tools, a protein-protein interaction (PPI) network was constructed, modules were analyzed, and enrichment analyses were performed. The expression and prognostic values of 14 hub genes were validated by the GEPIA database, and the correlation between hub genes and survival in lung adenocarcinoma was assessed by UALCAN, cBioPortal , String and Cytoscape, and Timer tools. Results. We found three genes (PIK3R1, SPP1, and PECAM1) that have a clear correlation with OS in the lung adenocarcinoma patient. It has been found that lung adenocarcinoma exhibits high expression of SPP1 and that this has been associated with poor prognosis, while low expression of PECAM1 and PIK3R1 is associated with poor prognosis P < 0.05 . We also found that the expression of SPP1 was associated with miR-146a-5p, while the high expression of miR-146a-5p was related to good prognosis P < 0.05 . On the contrary, the lower miR-21-5p on upstream of PIK3R1 is associated with a higher surviving rate in cancer patients P < 0.05 . Finally, we found that the immune checkpoint genes CD274(PD-L1) and PDCD1LG2(PD-1) were also related to SPP1 in lung adenocarcinoma. Conclusions. The results indicated that SPP1 is a cancer promoter (oncogene), while PECAM1 and PIK3R1 are cancer suppressor genes. These genes take part in the regulation of biological activities in lung adenocarcinoma, which provides a basis for improving detection and immunotherapeutic targets for lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: With life span extending, breast cancer (BC) survivors may face the possibility of developing second primary cancer (SPC) and considerably shorten survivorship. However, little is known about multiple primary cancer (MPC) patients with nonmetastatic breast cancer as a first primary malignancy (BCFPM). Methods: Here, we retrospectively analyzed data on cancer survivors with BCFPM diagnosed between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The prognostic factors for breast cancer‐specific survival (BCSS) were ascertained by the stepwise regression analysis and a competing risk model, and were integrated to the establishment of prognostic nomogram, of which the accuracy was measured by the calibration curve and the concordance index (C‐index). Results: In total, 8616 patients were identified with 4.6% of 3‐year breast cancer‐ specific death (BCSD) and 8.6% of 5‐year BCSD. The most common SPC among BCFPM patients were female BC and lung cancer. Besides, the median latency time between BC and SPC was 22 months. At a ratio of 7:3, all patients were randomly categorized into a training cohort (n = 6032) and a validation cohort (n = 2584). By a proportional subdistribution hazards regression analysis, the following factors were considered to own independent prognostic abilities of BCSS: subtypes, grade, T classification, N classification, radiation, and sites of SPC. The nomogram could accurately predict 3‐year and 5‐year breast cancer‐associated survival of BCFPM patients with high internal and external validated C‐index, 0.715 (95% CI, 0.691–0.739), and 0.683 (95% CI, 0.642–0.724), respectively. Conclusions: BC survivors remained a high risk of developing SPC and considerably shortened survival time. In this study, a favorable nomogram was constructed to as a prediction model for 3‐year and 5‐year BCSS of BCFPM patients, largely intending to prolong the life of these patients by assisting clinicians to make individualized follow‐up plans. [ABSTRACT FROM AUTHOR]