Eriocitrin, a lemons flavanone, exhibits several biological properties, antiproliferative, and proapoptotic effects. However, its molecular mechanical action is not entirely clarified. Oxidative stress causes abnormal stimulation of signal transducer and activator of transcription 3 (STAT3) and c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs) signaling has been strongly connected with the ruling of cell survival and apoptosis of cancer cells. Herein, we investigated an antiproliferative and proapoptotic effect that Eriocitrin modulates STAT3/MAPKs signaling activation in MCF-7 cells. We noticed that Eriocitrin strongly enhances reactive oxygen species (ROS) generation, alteration of mitochondrial outer membrane potential, and enhances apoptotic morphological changes. Furthermore, Eriocitrin suppressed STAT3 phosphorylation via inhibiting an upstream molecule of JAK2 and Src kinase activation, thereby blocking STAT3 nuclear translocation. Similarly, Eriocitrin causes oxidative stress-mediated JNK/p38 MAPK signaling activation. We confirmed that Eriocitrin induced ROS-mediated apoptosis inhibited by the antioxidant substance of N-acetylcysteine. Eriocitrin induced apoptosis via suppression of STAT3 signaling regulated proteins, activating proapoptotic factors Bax, caspase 7, 8, 9 and suppressing Bcl-2, Bcl-x expression in MCF-7 cells. Overall, these results evidenced that Eriocitrin can affect multiple signaling events associated with tumorigenesis. From this evidence, Eriocitrin, a novel chemotherapeutic agent, can be used to treat breast cancer.

Background: Luminal B cancers show much worse outcomes compared to luminal A. This present study aims to screen key lncRNAs and mRNAs correlated with luminal-B breast cancer. Methods: Luminal-B breast cancer tissue samples and adjacent tissue samples were obtained from 4 patients with luminal-B breast cancer. To obtain differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between luminal-B breast cancer tumor tissues and adjacent tissues, RNA-sequencing and bioinformatics analysis were performed. Functional annotation of DEmRNAs and protein-protein interaction networks (PPI) construction were performed. DEmRNAs transcribed within a 100 kb window up-or downstream of DElncRNAs were searched, which were defined as cis nearby-targeted DEmRNAs of DElncRNAs. DElncRNA-DEmRNA co-expression networks were performed. The mRNA and lncRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database to validate the expression patterns of selected DEmRNAs and DElncRNAs. Results: A total of 1178 DEmRNAs and 273 DElncRNAs between luminal-B breast cancer tumor tissues and adjacent tissues were obtained. Hematopoietic cell lineage, Cytokine-cytokine receptor interaction, Cell adhesion molecules (CAMs) and Primary immunodeficiency were significantly enriched KEGG pathways in luminal-B breast cancer. FN1, EGFR, JAK3, TUBB3 and PTPRC were five hub proteins of the PPI networks. A total of 99 DElncRNAs-nearby-targeted DEmRNA pairs and 1878 DElncRNA-DEmRNA co-expression pairs were obtained. Gene expression results validated in TCGA database were consistent with our RNA-sequencing results, generally. Conclusion: This study determined key genes and lncRNAs involved in luminal-B breast cancer, which expected to present a new avenue for the diagnosis and treatment of luminal-B breast cancer.

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Purpose PD-1 inhibitors have been routinely used to treat advanced non-small cell lung cancer (NSCLC) and have significantly improved clinical outcomes. In this study, we aimed to explore the influence of pretreatment fibrinogen-albumin ratio (FAR) on treatment response and survival in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. Patients and Methods A total of 91 patients with advanced NSCLC were included in the study. All patients received at least two cycles of systemic first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. Receiver operating characteristics analysis was performed to determine the optimal cutoff values of FAR. Univariate and multivariate analyses were used to identify independent prognostic factors, and the Kaplan–Meier method was used to estimate survival curves. Results Multivariate logistic regression analysis showed that N stage (N2-3) and high FAR (≥0.175, optimal cutoff value) were independent predictors for objective response rate (P = 0.0002, P = 0.0005, respectively). Multivariate Cox regression analysis of progression-free survival and overall survival showed that high FAR (≥0.145) was independent prognostic factors (P = 0.0061, P = 0.0024, respectively). Progression-free survival and overall survival were significantly shorter in the high FAR (≥0.145) group than those in the low FAR (<0.145) group (P = 0.0024, P = 0.0024, respectively). Conclusion Pretreatment FAR was an independent predictor for treatment response and independent prognostic factors in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy.

Purpose The purpose of this study is to compare the different EGFR mutation status in patients with metastatic non-small cell lung cancer (NSCLC) after first-line EGFR-TKIs therapy and analyze its relationship with efficacy and prognosis. Patients and Methods This study retrospectively analyzed the data of patients with metastatic NSCLC harboring EGFR mutation in the Affiliated Tumor Hospital of Guangxi Medical University from June 2016 to December 2020. Samples were collected before treatment and at the time of disease progression after first-line EGFR-TKIs therapy. Amplification refractory mutation system (ARMS) PCR and next-generation sequencing (NGS) were used to detect EGFR mutation. ORR, DCR, and PFS of different EGFR mutation groups were compared. Results The EGFR mutation rate of re-biopsy was 60.23%. The inconsistency rate of EGFR mutations in the same and different simple types was 72.22% (26/36) and 92.31% (48/52), respectively. Alterations in terms of EGFR mutations were divided into four groups: Group A: EGFR-sensitive mutation negative and T790M negative (39.77%); Group B: EGFR-sensitive mutation positive and T790M negative (18.19%); Group C: EGFR-sensitive mutation negative and T790M positive (36.36%); Group D: EGFR-sensitive mutation positive and T790M positive (5.68%). The differences between the four groups in ORR and DCR were not statistically significant (P>0.05). The median PFS of all patients was 10.65 months. PFS of Group A, B, C, and D was 12.26, 7.96, 10.55, and 13.81 months, respectively, with statistical significance (Log rank P = 0.014). Conclusion EGFR mutation status in metastatic NSCLC patients receiving the first- and second-generation TKIs after disease progression show diversity. Monitoring the EGFR mutation changes is of great importance for subsequent clinical decision-making and exploring the underlying mechanisms of acquired resistance.