Efficacy and Safety of Anti-HER2 Targeted Therapy for Metastatic HR-Positive and HER2-Positive Breast Cancer: A Bayesian Network Meta-Analysis.

Despite the development of HER2-targeted drugs, achieving favorable outcomes for patients with HR+/HER2+MBC remains challenging. This study utilized Bayesian Network Meta-analysis to compare the efficacy and safety of anti-HER2 combination regimens. The primary analysis focused on progression-free survival (PFS), while secondary analyses included objective response rate, overall survival (OS) and the incidence rate of grade 3/4 adverse events (AEs). A comprehensive search across seven databases identified 25 randomized controlled trials for inclusion in this meta-analysis. For patients eligible for endocrinotherapy, our findings revealed that dual-target combined endocrine therapy, such as Her2-mAb+Her2-mAb+Endo (HR = 0.38; 95%CrI: 0.16-0.88) and Her2-mAb+Her2-tki+Endo (HR = 0.45; 95%CrI: 0.23-0.89), significantly improved PFS compared to endocrine therapy alone. According to the surface under the cumulative ranking curves (SUCRAs), Her2-mAb+Her2-mAb+Endo and Her2-mAb+Her2-tki+Endo ranked highest in terms of PFS and OS, respectively. For patients unsuitable for endocrine therapy, anti-HER2 dual-target combined chemotherapy, such as Her2-mAb+Her2-mAb+Chem (HR = 0.76; 95%CrI: 0.6-0.96) and Her2-mAb+Her2-tki+Chem (HR = 0.48; 95%CrI: 0.29-0.81), demonstrated significant improvements in PFS compared to Her2-mAb+Chem. The results were the same when compared with Her2-tki+Chem. According to the SUCRAs, Her2-mAb+Her2-tki+Chem and Her2-mAb+Her2-mAb+Chem ranked highest for PFS and OS, respectively. Subgroup analyses consistently supported these overall findings, indicating that dual-target therapy was the optimal approach irrespective of treatment line.

Characterization of the promoter and 5'-UTR intron of oleic acid desaturase (FAD2) gene in Brassica napus.

In the present study, we characterized the transcriptional regulatory region (KF038144) controlling the expression of a constitutive FAD2 in Brassica napus. There are multiple FAD2 gene copies in B. napus genome. The FAD2 gene characterized and analyzed in the study is located on chromosome A5 and was designated as BnFAD2A5-1. BnFAD2A5-1 harbors an intron (1,192 bp) within its 5'-untranslated region (5'-UTR). This intron demonstrated promoter activity. Deletion analysis of the BnFAD2A5-1 promoter and intron through the ß-glucuronidase (GUS) reporter system revealed that the -220 to -1 bp is the minimum promoter region, while -220 to -110 bp and +34 to +285 bp are two important regions conferring high-levels of transcription. BnFAD2 transcripts were induced by light, low temperature, and abscisic acid (ABA). These observations demonstrated that not only the promoter but also the intron are involved in controlling the expression of the BnFAD2A5-1 gene. The intron-mediated regulation is an essential aspect of the gene expression regulation.